The Effects of Inhaled Pollutants on Reproduction in Marginalized Communities: A Contemporary Review

Abstract

Important differences in health that are closely linked with social disadvantage exist within and between countries. According to the World Health Organization, life expectancy and good health continue to increase in many parts of the world, but fail to improve in other parts of the world, indicating that differences in life expectancy and health arise due to the circumstances in which people grow, live, work, and age, and the systems put in place to deal with illness. Marginalized communities experience higher rates of certain diseases and more deaths compared to the general population, indicating a profound disparity in health status. Although several factors place marginalized communities at high risk for poor health outcomes, one important factor is exposure to air pollutants. Marginalized communities and minorities are exposed to higher levels of air pollutants than the majority population. Interestingly, a link exists between air pollutant exposure and adverse reproductive outcomes, suggesting that marginalized communities may have increased reproductive disorders due to increased exposure to air pollutants compared to the general population. This review summarizes different studies showing that marginalized communities have higher exposure to air pollutants, the types of air pollutants present in our environment, and the associations between air pollution and adverse reproductive outcomes, focusing on marginalized communities.

1. Introduction

Important differences in health that are closely linked with social disadvantage exist within and between countries (Closing the Gap in a Generation, 2008). According to the World Health Organization (WHO), life expectancy and good health continue to increase in parts of the world, but fail to improve in other parts of the world, indicating that differences in life expectancy and health arise due to the circumstances in which people grow, live, work, age, and seek medical care (Closing the Gap in a Generation, 2008). Age, poverty, and minority status are known to place some groups at disproportionately high risk for environmental disease (Gochfeld & Burger, 2011). Marginalized communities may be defined as those excluded from mainstream social, economic, educational, and/or cultural life. Examples include, but are not limited to, groups excluded due to race, sexual orientation, age, gender identity, language, immigration status, and/or physical ability (Sevelius et al., 2020).

Studies have shown disparities in health status in marginalized communities as evidenced by higher rates and risks of certain diseases and higher mortality rates compared to the general population (National Institute on Minority Health and Health Disparities, 2022). Studies in the United States have also shown that marginalized communities, including Black and Latina/Latino communities as well as those from low socioeconomic status (SES), have increased exposure to air pollutants compared to nonmarginalized communities (Jbaily et al., 2022). Interestingly, air pollutant exposure has been associated with adverse reproductive outcomes (Mahalingaiah et al., 2016; Nieuwenhuijsen et al., 2014; Radwan et al., 2016), suggesting that marginalized communities may be prone to present with higher rates of reproductive disorders due to higher air pollutant exposure than non-marginalized communities. However, limited information is available regarding the impact of exposure to air pollutants on reproductive outcomes in marginalized communities. In this review, we briefly describe marginalized communities and the evidence indicating that they are exposed to higher levels of air pollutants than the general population. Then, we briefly describe male and female reproductive physiology to give the reader an overview of the reproductive functions that might be affected by air pollutant exposure. Finally, we provide information on the different environmental contaminants found in air and their known reproductive effects.

Overall, this review summarizes current information on air pollutant exposure and reproductive outcomes, highlights gaps in our knowledge on the effects of air pollutants on reproductive outcomes, and encourages researchers from different disciplines to conduct research that helps us understand and mitigate reproductive health disparities. To do so, this review focuses on integrating the available data on air pollutant exposure and adverse reproductive outcomes in marginalized communities by: 1) summarizing different studies in which higher air pollutant exposures have been observed in marginalized communities compared to other non-marginalized communities and 2) summarizing some of the most relevant air pollutants present in our environment and their associations with adverse outcomes in male and female reproduction, with an emphasis on marginalized communities.

2. Methods

A search was conducted using PubMed to identify relevant epidemiological/human studies evaluating male and female adverse reproductive outcomes associated with air pollutant exposure in marginalized communities. Air pollutant searches included keywords such as particulate matter (PM), phthalates, pesticides, marijuana, electronic nicotine delivery systems, e-cigarettes, vaporizers, nitrogen dioxide, sulfur dioxide, and carbon monoxide. For air pollutant searches, we chose some of the most abundant air pollutants and those chemicals that are well known to affect reproduction and that have been recognized as important air pollutants. We considered reproductive outcomes to be those related to alterations in sperm and ovarian quality, alterations in sex steroid hormone levels, fertility, and fertility-related parameters such as birth outcomes. The evidence was then synthesized and summarized by air pollutant.

3. Marginalized communities, health disparities, and air pollution

Marginalized communities in North America experience higher rates of certain diseases and more deaths compared to the general population, indicating a profound disparity in health status (National Institute on Minority Health and Health Disparities, 2022). Although several factors place marginalized communities at high risk for poor health outcomes, one important factor is air pollutant exposure. Air pollution is defined as an increase in pollutant substances in the atmosphere due to human activity and natural sources (Mathiarasan & Hüls, 2021). Air pollutants derived from human activity include vehicle emissions, fuel oils, gas to heat homes, by-products of manufacturing and power generation, and fumes from chemical production. Natural sources include smoke from wildfires, ash and gases from volcanic eruptions, and gases such as methane that are emitted from decomposing organic matter in soils.

Human exposure to air pollution is a major health concern. According to the WHO, 7 million deaths each year are due to exposure to air pollution, 2.6 billion people primarily rely on polluting fuels and technologies for cooking, and 91% of the world’s population lives in places where air pollution levels exceed WHO guideline limits (World Health Organization, 2022a). Importantly, air pollutant exposure has been associated with reproductive toxicity and infertility in several studies (Cao et al., 2015; Gai et al., 2017; Mahalingaiah et al., 2016; Nieuwenhuijsen et al., 2014; Radwan et al., 2016). Air pollutants can be present as gases, liquid droplets, or particles and are classified as gaseous pollutants, organic compounds, heavy metals, and particulate matter (Kampa & Castanas, 2008). Domestic use of fuels such as wood fuel or solid fuel for different needs in low income houses exposes people to indoor pollution, increasing exposure to different air pollutants (Manisalidis et al., 2020). Some common household air pollutants include combustion derived compounds such as particulate matter, black carbon, polycyclic aromatic hydrocarbons (PAHs), carbon monoxide, and methane, whereas non-combustion sources include radon, lead, and volatile organic compounds (World Health Organization, 2022b). However, endocrine disrupting chemicals, agents known to affect normal synthesis, secretion, transportation, binding and metabolism of natural hormones, such as phthalates, polychlorinated biphenyls, brominated flame retardants, dioxins, alkylphenols, perfluorinated chemicals, pesticides, and nanoparticles can also be found in indoor and outdoor air (Annamalai & Namasivayam, 2015; Huang et al., 2020; Rabajczyk et al., 2020).

Marginalized and minority communities are exposed to higher levels of air pollutants than the majority population (Table 1). A study evaluating phthalate metabolite concentrations across full-term pregnancies found that non-White women had higher urinary levels of phthalates compared to White women, with some levels being especially high in non-Hispanic Black and Hispanic women across pregnancy (James-Todd et al., 2017). Another study found that traffic and air pollution exposures, as well as risk for adverse health outcomes, were higher in minorities and low SES groups and lower in White and high SES groups compared to the mean (Pratt et al., 2015). Jbaily et al. (2022) found that areas with higher-than-average Black, Asian, Hispanic, or Latino populations were consistently exposed to higher levels of PM_2.5 than areas with White populations (Jbaily et al., 2022). Interestingly, the same study found that although average PM_2.5 levels decreased from 2000 to 2016, disparities in exposure continued to increase over time among racial/ethnic groups. Similarly, air pollution concentrations are increasing in low- to middle-income countries while decreasing in high income countries due to industrialization (Mathiarasan & Hüls, 2021; J. Wang et al., 2017). Marginalized people are also at significantly increased risk of pesticide exposure via inhalation because their communities are often located in areas with heavy industrial pollution and poor housing conditions, which lend themselves to increased pesticide use. In fact, a screening study conducted throughout California found that compared to other environmental pollutants, the burden of pesticide pollution had the greatest racial, ethnic, and income disparities in the state (Cushing et al., 2015). The same study reported that almost all pesticide use in the state of California occurs in the 60% of California zip codes that have the highest percentage of people of color (Cushing et al., 2015).

Table 1.

Exposure of marginalized communities to air pollutants

Chemical	Location	Study type/Analysis	Main findings	Reference
Traffic and air pollution	Minnesota, USA	Cumulative exposures and risks from traffic and from MNRiskS-modeled air pollution in multiple source categories across demographic groups	-Traffic exposure and air pollution risks from all sources positively correlated with minorities (Black, Native American, Hispanic, Black) and measures of low SES	(Pratt et al., 2015)
PM2.5	USA	Data platform linking demographic and PM2.5 data across the USA	-Areas with higher-than-average Black, Asian, and Hispanic or Latino populations were exposed to higher levels of PM2.5 than areas with White populations -Population-weighted average of PM2.5 decreased by 40% from year 2000 (12.6 μg m−3) to 2016 (7.5 μg m−3), but disparities in exposure increased over time among racial/ethnic groups	(Jbaily et al., 2022)
PM2.5	Northern hemisphere	Integrated exposure-response model developed by Health Effects Institute	- From 1990 to 2010 PM2.5 mortalities decreased by 67% and 58% in Europe and North America, while they increased by 21% and 85% in East Asia and South Asia -Air pollution concentrations are increasing in low- to middle-income countries while decreasing in high income countries	(J. Wang et al., 2017)
Pesticides used in the state of California	California, USA	Data from the CalEnviroScreen- a statewide environmental screening tool	-60% of the zip codes with the highest proportion of residents of color host more than 95% of pesticide use in the state of California	(Cushing et al., 2015)
PM2.5 and PM10	USA	Population data via US Census Bureau’s 2009 to 2013 American Community Survey; Emissions data collected from the US EPA National Emissions Inventory	-People in poverty had 1.35 times higher burden of living close to PM2.5 and PM10 emitting facilities than the overall population -Non-Whites had 1.28 and 1.27 times higher burden of living close to PM2.5 and PM10 emitting facilities than the overall population -Blacks had 1.54 and 1.49 times higher burden of living close to PM2.5 and PM10 emitting facilities than the overall population	(Mikati et al., 2018)
PM2.5	USA	Data from the 2014 EPA National Emissions Inventory	-Estimated total average PM2.5 is 6.5 μg m−3 for the US general population -Estimated total average PM2.5 is 7.9 μg m−3 for Blacks, 7.2 μg m−3 for Hispanics, and 7.7 μg m−3 for Asians -Most emission source types disproportionately affect racial-ethnic minorities	(Tessum et al., 2021)
Organophosphates, Pyrethroids, Organochlorines, Phenoxy-herbicides	USA	Data from the CDC’s Fourth National Report on Human Exposure to Environmental Chemicals	-Non-Hispanic Blacks and Mexican Americans had higher average urinary and blood levels than the general population	(Donley et al., 2022)
Aromatic hydrocarbons and organochlorine pesticides	USA	Data from the NHANES 1999-2014	-Women of color had higher concentrations of pesticide metabolites than White women	(Nguyen et al., 2020)
Organochlorine pesticides	Long Island, NY, USA	Case-control study	-Breast adipose tissue of Black women contained 10% more pesticide biomarkers than the adipose tissue of White women	(Muscat et al., 2003)
Aromatic hydrocarbons and organochlorine pesticides	USA	Data from the NHANES and EPA’s ToxCast program	-The blood and urine of non-Hispanic Black women had higher levels of pesticide metabolites compared to non-Hispanic White women	(Polemi et al., 2021)
Organophosphate, carbamate, and phthalamide pesticides	New York City, NY, USA	Biomonitoring of urban minority mothers and newborns	-Pesticides were detected in 100% of personal air samples and in up to 83% of maternal or umbilical cord plasma samples -Pesticides detected in personal air samples were highly correlated to levels of the same pesticides or their metabolites in maternal and umbilical cord plasma levels	(Whyatt et al., 2003)
Organophosphate and dithiocarbamate pesticides	Florida, USA	Cross-sectional survey	-Hispanic and Haitian female farmworkers had higher levels of pesticide metabolites in their urine compared to the national averages reported in the Disease Control and Prevention NHANES	(Runkle et al., 2013)
Pesticides used in the State of Idaho	Idaho, USA	Biomonitoring of Latina/Latino farm workers	-Pesticide metabolites were detected in the urine of all Latina/Latino farmworkers and many of these metabolites persisted after the spraying season was over	(C. Curl et al., 2019)
e-Cigarettes	England	Cross-sectional study (n= 34,442)	-E-cigarette use was more common among those from low SES than those from higher SES (OR: 1.59; 95% CI: 1.05-2.40; P=.03)	(Kock et al., 2020)
Phthalates	Charleston, SC, USA	Cross-sectional study (n= 378 pregnant women)	-Significantly elevated concentrations of six phthalate metabolites in African American women compared to Caucasian women -Significantly higher phthalate concentrations in women from low SES compared to higher SES	(Wenzel et al., 2018)
Phthalates	Massachusetts, USA	Nested case-control study (Lifecodes pregnancy cohort)	-Baseline specific gravity-adjusted geometric mean MEP urinary level of 286 μg/l for Non-Hispanic Blacks compared to 98.7 μg/l for Non-Hispanic Whites -Concentrations of MBP, MEP, MiBP, and MBzP significantly higher among non-Hispanic Blacks and Hispanics during early first trimester -Non-Hispanic Blacks and Hispanic women have substantially higher levels of MEP and MCPP compared to non-Hispanic White women	(James-Todd et al., 2017)

MEP: Mono-ethyl phthalate, SG: Specific gravity, MBP: Mono-butyl phthalate, MiBP: Mono-isobutyl phthalate, MBzP: Mono-benzyl phthalate, MCPP: Mono-(3-carboxypropyl) phthalate, SES: Socioeconomic status, OR: odds ratio, CI: Confidence Interval, PM: Particulate matter, NHANES: National Health and Nutrition Examination Survey.

4. Inhaled pollutants can reach the male and female reproductive systems

Due to a large internal surface area that is continually exposed to ambient air, the respiratory system is one important route of exposure to pollutants. Air pollutants can enter the general bloodstream through the thin blood-gas barrier. Air pollutants can be absorbed by human tissues or dissolved in body fluids, depending on their hydrophilicity and hydrophobicity (D. Kim et al., 2018). The high surface area of smaller particles in air allows them to adsorb large amounts of substances including organic and inorganic compounds (Nakane, 2012). Airborne particles can be deposited in different pulmonary regions after inhalation. After deposition, particles have been shown to readily translocate to extrapulmonary sites and reach other target organs through the vasculature (Peters et al., 2006) (Figure 1). As reviewed by Nakane (2012), several in vivo studies have confirmed the translocation and distribution of a diverse variety of pollutants to different organs after deposition in the respiratory system, demonstrating that inhaled pollutants can reach different organs and exert toxicity (Nakane, 2012).

Figure 1. Inhaled pollutants are linked with adverse reproductive functions.

Exposure to air pollutants results in inhalation of pollutants and distribution into the respiratory tract (1). Afterwards, air pollutants can enter the general bloodstream (2), become distributed through the body, and ultimately reach and affect the reproductive tissues in exposed males and females (3).

Reproductive organs such as the testes in males, and the ovaries, uterus, and placenta in females are highly vascularized and have high rates of blood flow (Findlay, 1986; Rizzoto et al., 2018). The testes are vascularized organs (Findlay, 1986), and testicular blood flow increases with decreased inspired oxygen levels (Rizzoto et al., 2018). Importantly, some studies have associated air pollutant exposure with lower levels of oxygen (Kargarfard et al., 2011; Luttmann-Gibson et al., 2014), suggesting that decreased oxygen levels due to air pollution may increase the blood flow to the testes, and therefore, increase testicular exposure to air pollutants. In the ovaries and uterus, development of new blood vessels is essential for proper supply of nutrients and hormones (Reynolds et al., 2002; Shimizu et al., 2012). The ovaries are highly vascularized organs, and a fenestrated blood vascular network supplies the late stages of developing ovarian follicles, contributing to the formation of follicular fluid (Brown & Russell, 2014). This suggests that different follicle populations might be exposed to pollutants from the blood in different manners based on their blood supply. Accumulation of air pollutants in reproductive organs is plausible because similar concentrations of pollutants such as bisphenol A and perfluoroalkyl substances have been found in the serum and follicular fluid (Björvang et al., 2022; Ikezuki et al., 2002) and female reproductive effects have been found after exposure to different pollutants (Chiang et al., 2017). However, the effects of air pollutants on reproduction may also be due to effects on the neuroendocrine system, which controls gonadal function through the hypothalamus-pituitary-gonadal axis (HPG) (Plant, 2015).

5. The hypothalamic-pituitary-gonadal axis and reproductive physiology

Reproduction in males and females is driven by the concerted actions of the HPG axis (Meccariello et al., 2014; Mikhael et al., 2019). The HPG axis is a tightly regulated feedback loop controlling a number of reproductive functions, including steroid hormone production and gamete formation (Meccariello et al., 2014; Mikhael et al., 2019). The hypothalamus produces and secretes the peptide hormone gonadotropin-releasing hormone (GnRH) (Plant, 2015). GnRH targets the gonadotrope cells in the anterior pituitary, stimulating the cells to release the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), into systemic circulation (Plant, 2015). LH and FSH target the ovaries and testes to drive production of steroid hormones, such as estrogen, progesterone, and testosterone (Andersen & Ezcurra, 2014; Eacker et al., 2008). These steroid hormones can feedback to the hypothalamus and anterior pituitary to block the release of GnRH and LH and FSH, respectively, and therefore regulate their own production (Plant, 2015). HPG axis function is sensitive to disruption by inhaled environmental chemicals (Plunk & Richards, 2020).

5.1. Male reproductive physiology

In males, LH and FSH target their cognate receptors in the testes. The testes are male reproductive structures that produce spermatozoa (male gametes) and sex steroid hormones. The testes contain a network of coiled tubules called the seminiferous tubules. The interstitium surrounding the seminiferous tubules contains a population of LH receptor expressing cells called the Leydig cells (Lei et al., 2004). In response to LH, Leydig cells convert cholesterol into testosterone (Eacker et al., 2008). Testosterone and dihydrotestosterone (DHT) act through the androgen receptor to drive the development of male sexual characteristics and facilitate spermatogenesis (Matsumoto et al., 2013). The seminiferous tubules contain a population of FSH receptor expressing cells called Sertoli cells (Oduwole et al., 2018). FSH stimulation increases Sertoli cell proliferation (Oduwole et al., 2018). Additionally, FSH acts through Sertoli cells to promote spermatogenesis (Oduwole et al., 2018; Ramaswamy & Weinbauer, 2014).

Testosterone originating from LH-stimulated Leydig cells works in concert with FSH in the Sertoli cells to produce molecular factors and nutrients to support spermatogenesis (Oduwole et al., 2018). Immature spermatogonia reside along the basal lamina of the seminiferous tubules (Linn et al., 2021). As spermatogonia mature, they move away from the basal lamina towards the lumen and develop into spermatocytes, then spermatids, and finally, immature sperm (Linn et al., 2021). Following spermatogenesis, immature sperm travel to the epididymis, where they undergo further maturation, gain motility and fertilization capabilities, and are stored until ejaculation (James et al., 2020). The onset of sperm production at puberty signals reproductive maturity and continues through adulthood (Vermeulen, 1993). In the aging male, sperm concentration appears to be unaffected by age, whereas sperm motility, morphology, and seminal volume decline with age (Harris et al., 2011).

5.2. Female reproductive physiology

Female reproduction is regulated by orchestrated events occurring in the HPG axis. In humans, the menstrual cycle occurs over approximately 28 days and is divided into the menses phase, the follicular phase, and the luteal phase (Reed & Carr, 2000). These phases are characterized by distinctive changes in hormone profiles, ovarian histology, and uterine architecture to facilitate pregnancy (Reed & Carr, 2000). In the absence of pregnancy, the uterine lining is shed during the menses phase and the cycle repeats itself.

LH and FSH target receptors in the ovary and drive principal ovarian functions, including folliculogenesis and steroidogenesis. The ovary is a reproductive tissue containing different populations of ovarian follicles. A mature ovarian follicle is comprised of an oocyte surrounded by layers of granulosa cells and theca cells (Gershon & Dekel, 2020). During folliculogenesis, immature primordial follicles mature sequentially into primary, preantral (secondary), antral, and preovulatory follicles (Gershon & Dekel, 2020). This process is characterized by an increase in follicle size, expansion of the granulosa cell population, formation of thecal cell layers, and formation of the antrum, a fluid filled space within the follicle (Gershon & Dekel, 2020). A surge in LH triggers ovulation, wherein the preovulatory follicle ruptures and releases the oocyte into the oviduct for possible fertilization (Duffy et al., 2019). The remaining tissue from the ruptured follicle forms a specialized structure called the corpus luteum (Duffy et al., 2019). With each menstrual cycle, multiple follicles are recruited for maturation, but typically only one follicle is ovulated while the remaining follicles degenerate through follicular atresia (McGee & Hsueh, 2000).

As immature follicles develop into antral follicles, they gain the capacity for steroidogenesis. Steroidogenesis is the generation of sex steroid hormones through the concerted actions of theca and granulosa cells within the follicle (Reed & Carr, 2000). This process is mediated by steroidogenic enzymes, converting cholesterol precursor molecules into progesterone, androgens, and estrogens (Reed & Carr, 2000). During the follicular phase, estrogen is the dominant hormone produced by the ovary (Reed & Carr, 2000). Following ovulation, the corpus luteum produces high levels of progesterone and lower levels of estrogen (Reed & Carr, 2000). Estrogen and progesterone are released from the ovary into the systemic circulation where they can reach target tissues, including the pituitary to exert feedback on the HPG axis and the mammary gland to promote morphogenesis (Plant, 2015; Stingl, 2011).

The uterus is a primary target for ovarian estrogen and progesterone. During the menses phase, when hormone levels are low, the endometrium, or inner uterine lining, is shed (Reed & Carr, 2000). During the follicular phase, increasing estrogen levels drive the endometrium to proliferate and thicken to prepare for pregnancy (Monis & Tetrokalashvili, 2022). During the luteal phase, when the corpus luteum is producing estrogen and progesterone, the endometrium differentiates and undergoes structural and functional changes to support embryo implantation in the event of pregnancy (Ng et al., 2020). In the absence of pregnancy, the corpus luteum regresses, estrogen and progesterone levels fall, and menses commences (Reed & Carr, 2000).

5.3. Pregnancy

Sexual intercourse during the window of time surrounding ovulation can result in fertilization of the released oocyte, giving rise to an embryo. The embryo travels down the oviduct into the uterus, where it can invade and implant into the receptive endometrium primed by estrogen and progesterone during the luteal phase (Ng et al., 2020). The endometrium will provide nutrition and support for the growing embryo until the placenta forms (Ng et al., 2020). The placenta is a transient structure formed from both fetal and maternal-derived tissues (Burton & Fowden, 2015). The placental barrier allows for exchange of nutrients, oxygen, and waste while preventing maternal blood from coming into contact with the fetus during development (Burton & Fowden, 2015). However, despite this barrier, environmental chemicals are detectable in amniotic fluid, suggesting that certain chemicals can cross the barrier and lead to exposure of the fetus during gestation (Tang et al., 2020). Gestation is characterized by rapid cell division, organogenesis, tissue formation, and fetal growth, making it a sensitive window for toxicant exposure (Padmanabhan et al., 2021). Gestational chemical exposures can be reflected by adverse pregnancy and birth outcomes, including maternal complications, preterm birth, and changes in birth weight and size (Padmanabhan et al., 2021).

6. Particulate matter

Particulate matter (PM) is a main component of air pollution and is known to induce adverse health effects (Dhananjayan et al., 2019). In general, PM is classified as PM₁₀ (particles ≤ 10 μm in diameter), PM_2.5 (particles ≤ 2.5 μm in diameter), and PM_0.1 (particles ≤ 0.1 μm in diameter), or ultrafine particles (UFP) (Dhananjayan et al., 2019). It is important to emphasize that particles with nano sizes (nanoparticles; 1-100 nm) are present in air as a result of human activity and natural processes (Dhananjayan et al., 2019). Particles in the nano size range constitute 20% of particle mass, and more than 90% of diesel-generated particles and nanoparticles are generated from indoor activities including cooking, smoking, cleaning, and combustion (Dhananjayan et al., 2019). Over half the particles in the air are less than 100 nm, and particle count, which reflects the sub 100 nm component, is the metric that best relates to the risk of heart attack (Seaton et al., 2010), highlighting a main role of the nanometer-size component in the toxicity of air pollution.

A study evaluating disparities in distribution of PM emission sources in the US found that for PM_2.5 or less, communities living in poverty had a 1.35 times higher burden than did the overall population, and that Black people had a 1.54 times higher burden than the overall population (Mikati et al., 2018). Accordingly, another study found that the estimated total average PM_2.5 from all domestic anthropogenic sources is 6.5 μg/m³ for the US general population, and that exposures are higher for Blacks, Hispanics, and Asians and lower for Whites than the average (Tessum et al., 2021) (Table 1).

A study was conducted in California to evaluate the associations between traffic-related air pollution during pregnancy and preterm birth (Padula et al., 2014). The authors found increased odds ratios for early preterm birth for those exposed to the highest quartile of PM₁₀ and PM_2.5 during the second trimester and the end of pregnancy (Padula et al., 2014). Interestingly, associations were stronger among mothers with low SES compared to women with higher SES (Padula et al., 2014). Another study evaluating the effect of air pollutants on the risk of stillbirth found that for PM_2.5, the risk of stillbirth was higher in non-Hispanic Black women than in the rest of the maternal race groups, but also that women who had stillbirths were less educated and less likely to have had any prenatal care than women who did not have stillbirths (Faiz et al., 2012) (Table 2). Studies have also found associations between air pollution exposure and male fertility alterations (Jurewicz et al., 2018). As reviewed by Jurewics et al. (2018), exposure to air pollutants such as PM_2.5 and PM₁₀ resulted in alterations in sperm parameters (sperm concentration, motility, and morphology) and affected the levels of reproductive hormones in men (Jurewicz et al., 2018).

Table 2.

Effects of air pollutants on reproduction in marginalized communities

Chemical	Location	Study type/Analysis	Main findings	Reference
PM2.5 and PM10	California, USA	Logistic regression analysis (n=263,204 women)	-Early preterm birth for pregnant women exposed to the highest quartile of PM10 during the second trimester of pregnancy (OR=2.80; 95% CI: 2.26-3.47) was higher for low SES women (OR=3.98; 95% CI: 2.66-5.98) -Early preterm birth for pregnant women exposed to the highest quartile of PM2.5 during the second trimester of pregnancy (OR=2.83; 95% CI: 2.29-3.50) was higher for low SES women (4.30; 95% CI: 2.85-6.48) -Strong associations between preterm birth and PM exposure that were higher in low SES mothers	(Padula et al., 2014)
PM2.5	New Jersey, USA	Generalized estimating equation models. Data from US EPA Air Quality System and New Jersey Department of Health	-Stillbirths were increased with each 4 μg/m3 increase in PM2.5 in the first (OR=1.15, 95% CI: 0.96-1.37) and second (OR=1.14, 95% CI: 0.96-1.35) trimesters -Highest risk of stillbirth in non-Hispanic Blacks (37.8% non-Hispanic Black compared to 29.4% non-Hispanic-White) -Women who had stillbirths were less educated than women without stillbirths	(Faiz et al., 2012)
Wood smoke	Sub-Saharan Africa	Systematic literature search	-Mean personal PM2.5 26.3-1574 μg/m3 (range: 26.3 ± 1.48 μg/m3 to 1574 ± 287 μg/m3) -Mean personal CO 0.64-22 ppm (range: 0.64 ±2.12 ppm to 22 ±2.4) -Positive associations for woodsmoke exposure and LBW, non-syndromic cleft lip, cleft palate, and child mortality -Use of wood fuels in domestic cooking is the major source of wood smoke -Females were exposed to higher levels than males	(Bede-Ojimadu & Orisakwe, 2020)
Charcoal and garbage burning	Accra, Ghana	Cross-sectional study (n=592 mothers)	-Increased risk of LBW for use of charcoal (RR= 1.41; 95% CI: 0.62, 3.23) compared to use of LPG -Increased risk of LBW for garbage burning (RR= 2.95; 95% CI: 1.10, 7.92) compared to use of LPG -Increased risk of LBW for combined charcoal use and household garbage burning (RR= 4.16: 95% CI: 2.02, 8.59)	(Amegah et al., 2012)
Indoor Air Pollution	Cape Coast, Ghana	Cross-sectional study (n=559 mothers)	-Indoor air pollution mediated observed effects of socioeconomic deprivation on birth weight (10-62%) -Increased risk of LBW among low income mothers (RR: 3.18; 95% CI:1.41-7.21) -Increased risk of preterm birth among low income mothers (RR: 1.83; 95% CI: 1.31-2.56) -Low SES was associated with increased risk of low body weight (4.57; 95% CI: 1.67-12.49)	(Amegah et al., 2013)
NO2, SO2, and CO	New Jersey, USA	Generalized estimating equation models. Data from US EPA Air Quality System and New Jersey Department of Health	-Stillbirths were increased with each 10 ppb increased in NO2 in the first trimester (OR=1.16, 95% CI: 1.03-1.31) -Highest risk of stillbirth in non-Hispanic Blacks (42.9% non-Hispanic Black compared to 27.5% non-Hispanic-white maternal race for stillbirths) -Stillbirths were increased with each 3 ppb increased in SO2 in the first (OR=1.13, 95% CI: 1.01-1.28) and third trimester (OR=1.03, 95% CI: 1.03-1.37) -Highest risk of stillbirth in non-Hispanic Blacks (35.4% non-Hispanic Blacks compared to 30.1% non-Hispanic-White maternal race for stillbirths) -Stillbirths were increased with each 0.4 ppb increased in CO in the second (OR=1.14, 95% CI: 1.01-1.28) and third trimester (OR=1.14, 95% CI: 1.06-1.24) -Highest risk of stillbirth in non-Hispanic Blacks (35% non-Hispanic Blacks compared to 29.6% non-Hispanic-Whites maternal race)	(Faiz et al., 2012)
NO2 and CO	California, USA	Logistic regression analysis (n=263,204 women)	-Early preterm birth for pregnant women exposed to the highest quartile of CO during the second trimester of pregnancy (OR=1.92; 95% CI: 1.52-2.42) - Early preterm birth for pregnant women exposed to the highest quartile of CO during the second trimester of pregnancy (OR=1.60; 95% CI: 1.28-2.01)	(Padula et al., 2014)
Organophosphate pesticides	New York City, NY, USA	Urban minority cohort	-Chlorpyrifos and diazinon were inversely associated with birth weight and length	(Whyatt et al., 2004)
Organophosphate pesticides	New York City, NY, USA	Urban minority cohort	-Chlorpyrifos was associated with decreased birth weight among African Americans and decreased birth length in Dominicans	(Perera et al., 2003)
Organophosphate pesticides	Salinas Valley, CA Cincinnati, OH New York, NY	Pooled cohorts	-Among non-Hispanic Black women, increasing urinary concentrations of organophosphate metabolites were associated with decreased birth length	(Harley et al., 2016)
Organophosphate, organochlorine, and phthalamide pesticides	California, USA	Case control of Latina women	-Occupational exposure to these pesticides was associated with increased risk of breast cancer	(Mills et al., 2019)
Organophosphate pesticides	Salinas valley, CA, USA	cohort of low-income, Latina women	-In utero pesticide exposure was associated with decreased gestational duration	(Eskenazi et al., 2004)
Marijuana	California, USA	Population-based, retrospective cohort study of mother-infant pairs; 40474 participants	-Prenatal cannabis use disorder was associated with small for gestational age (OR = 1.13, 95% CI = 1.08-1.18), preterm birth (OR = 1.06, 95% CI = 1.01-1.12), low birth weight (OR = 1.13, 95% CI = 1.07-1.20), and death within 1 year of birth (OR = 1.35, 95% CI = 1.12-1.62) -Prenatal cannabis use disorder in Hispanic participants was associated with preterm birth (OR = 1.11, 95% CI = 1.00-1.23) and infant death within 1 year (OR = 2.51, 95% CI = 1.62-3.89) -Prenatal cannabis use disorder in Black participants was associated with small for gestational age (OR = 1.31, 95% CI = 1.20-1.43) and low birth weight (OR = 1.23, 95% CI = 1.10-1.36)	(Shi et al., 2021)

LPG: liquefied petroleum gas, SES: socioeconomic status, LBW: low birth weight, RR: Risk ratio, PM: Particulate matter, OR: odds ratio, CI: Confidence Interval

Wood smoke is still a major source of energy for populations in developing countries (Bede-Ojimadu & Orisakwe, 2020). Wood smoke is a complex mixture of gases, liquids, and solids, but particulate matter, specifically PM_2.5, is of most concern (Bede-Ojimadu & Orisakwe, 2020). Recently, a study showed that the mean personal PM_2.5 ranged from 26.3 to 1574 μg/m³ in a Sub-Saharan African population exposed to wood smoke, which is higher than the WHO’s Air Quality Guideline for 24-hour mean exposure (Bede-Ojimadu & Orisakwe, 2020). Interestingly, wood fuels in domestic cooking are the main source of exposure, and women are exposed to higher levels of wood smoke than men (Bede-Ojimadu & Orisakwe, 2020). Further, wood smoke is associated with respiratory diseases as well as low birth weight, non-syndromic cleft lip and/or cleft palate, and mortality under the age of five (Bede-Ojimadu & Orisakwe, 2020). Ghana is an underdeveloped country where women are considered to be a marginalized group (Afra Boateng, 2020). In a cross-sectional study in Ghana, maternal use of charcoal as a cooking fuel during pregnancy and burning of garbage at home were found to be strong determinants of average fetal growth and risk of low birth weight (Amegah et al., 2012). Interestingly, around 60% of the population in the study was from low social class and had low educational level (Amegah et al., 2012). Another study conducted in Ghana found an association between low SES and low birth weight (Amegah et al., 2013). According to the study, living in a poor neighborhood resulted in a 221 g reduction in birth weight, and low education resulted in a reduction of 187 g in birth weight. Interestingly, causal pathway analysis showed indoor fuel pollution mediating a substantial proportion of the observed effects (Amegah et al., 2013) (Table 2).

7. Gaseous pollutants

The Centers for Disease Control and Prevention consider six pollutants as “criteria” air pollutants (Air Pollutants | Air | CDC, 2022). Criteria pollutants include carbon monoxide (CO), lead, nitrogen oxides, ozone, PM, and sulfur dioxide (Air Pollutants | Air | CDC, 2022). Activities such as tobacco smoke, exhaust from cars, and woodburning require the combustion of fuels such as natural or liquefied petroleum gas, fuel oil, kerosene, wood, or coal. After combustion, the most commonly produced pollutants include some of the criteria air pollutants such as CO, nitrogen dioxide, and sulfur dioxide (US EPA, 2019). In the previous section, we reviewed the studies focusing on PM and included some studies focusing on wood fuels. However, it is interesting to note that other pollutants such as CO, nitrogen oxides, and sulfur dioxide, present as part of the combustion process, might adversely affect reproduction (Faiz et al., 2012; Padula et al., 2014).

A study evaluated the risk of stillbirth and ambient air pollution using data from New Jersey (from 1998 to 2004) and generalized estimating equation models to estimate the relative odds of stillbirth associated with interquartile range increases in mean air pollutant concentrations in the first, second, and third trimesters and throughout the entire pregnancy (Faiz et al., 2012). The authors found that the relative odds of stillbirth were significantly increased with each 10-ppb increase in mean nitrogen dioxide concentration in the first trimester (OR:=1.16, 95% CI: 1.03-1.31), each 3-ppb increase in mean sulfur dioxide concentration in the first (OR= 1.13, 95% CI: 1.01-1.28) and third (OR: 1.26, 95% CI: 1.03-1.37) trimesters, and each 0.4-ppm increase in mean CO concentration in the second (OR=1.14, 95% CI: 1.01-1.28) and third (OR:1.14, 95% CI: 1.06-1.24) trimesters (Faiz et al., 2012). Interestingly, the risk of stillbirth was highest for non-Hispanic Black women for NO₂, SO₂, and CO (Faiz et al., 2012). Further, the authors found that for all pollutant-specific analyses, the risk of still birth was highest in non-Hispanic Blacks and lowest in other non-Hispanic women (Faiz et al., 2012). A study in California used logistic regression analysis to evaluate associations between air pollutant exposure and risk of preterm birth (Padula et al., 2014). The authors found increased OR for early preterm birth for those women exposed to the highest quartile of CO and NO₂ during the second trimester and the end of pregnancy (adjusted OR 1.4-2.8) (Padula et al., 2014). Interestingly, the associations were stronger among mothers with low SES (adjusted OR 2.1-4.3) compared to women with higher SES (Padula et al., 2014). The authors confirmed associations between traffic-related air pollution and prematurity, particularly among very early preterm births and low SES neighborhoods (Padula et al., 2014). In a cohort study in the Czech Republic, short-term effects of atmospheric pollutants on fecundability were characterized (Slama et al., 2013). NO₂ levels were associated with decreased fecundability in approximately 2000 couples trying to conceive (Slama et al., 2013). However, the authors did not examine specific groups to determine whether ethnicity, race, education, or socioeconomic level might increase the risk (Slama et al., 2013). Despite the few published studies, little is known about gaseous pollutants such as NO₂, SO₂, ozone, and CO and their effects on reproduction, as well as if disproportionate exposures to NO₂, SO₂, ozone, and CO increase the risk of adverse reproductive outcomes in marginalized populations. More research is needed to better understand the risk of gas pollutants exposure into these communities.

8. Pesticides

Pesticides are chemicals used to eradicate pests including weeds, insects, fungi, and rodents. They are primarily used in commercial agricultural systems and in private residences for pest control and gardening. Humans are exposed to pesticides primarily through ingestion of contaminated food and water and through dermal contact when using pesticides (Coscollà et al., 2017; López et al., 2017). Recently, pesticide residues have been detected in the gas phase and particulate phase (PM_2.5-10) of outdoor air in both agricultural and urban communities worldwide (Amaral Dias et al., 2021; Coscollà et al., 2017; Li et al., 2014; López et al., 2017; Nascimento et al., 2017; Weppner et al., 2006). Pesticide residues have also been detected in air, dust, and surface samples within homes, schools, and child-care centers in both agricultural and urban communities worldwide (Alkon et al., 2022; Bradman et al., 2007; Butte & Heinzow, 2002; Harnly et al., 2009; Lu et al., 2013; Morgan, 2012; Pauluhn, 1996; Wason et al., 2013).

Marginalized populations are at elevated risk of pesticide inhalation because they live near pesticide manufacturing facilities and toxic waste sites, which are often contaminated with legacy pesticides (Poisonous Homes, 2020). An analysis of US pesticide manufacturing facilities in significant violation of environmental laws such as the clean air act and the clean water act revealed that 44% of the residents within one mile of these facilities had incomes less than two times the federal poverty level (Donley et al., 2022). In addition to existing facilities, new manufacturing plants are disproportionately being built in lower income communities with higher proportions of people of color (Mohai & Saha, 2015; Pastor et al., 2001).

In addition to living in neighborhoods with high environmental pesticide contamination, residential pesticide use is elevated in low-income homes as a result of crowded living conditions, poor maintenance, pest infestations, and old age of housing structures (Landrigan et al., 1999; Quirós-Alcalá et al., 2011). Apartment units were analyzed in a study of public housing facilities in Boston, MA, where 98% of residents identified as Hispanic or Black (Julien et al., 2008). At least two pesticides were detected in all the units, and six pesticides were identified in almost all the units (Julien et al., 2008). A survey conducted by the state of New York reported that 80% of low-income public housing facilities applied pesticides inside apartments and in common areas on a regular basis (Surgan et al., 2022). Another study conducted in California compared pesticide residues in the house dust of low income homes in urban and agricultural communities and found no major differences in the types or concentrations of pesticides found in the house dust (Quirós-Alcalá et al., 2011), suggesting the risk of indoor airborne pesticide exposure depends more on SES than proximity to agricultural land.

Agricultural workers are vulnerable to pesticide inhalation because pesticides are most commonly applied to crops through spray and fog, especially by individuals working in greenhouses (Gustin et al., 2005). The occupational hazards associated with pesticide inhalation are further compounded by the fact that most agricultural workers in the US belong to marginalized communities. According to the National Agricultural Workers Survey (NAWS), 83% of farmworkers identify as Hispanic or Latina/Latino (Findings from the National Agricultural Workers Survey (NAWS) 2017–2018: A Demographic and Employment Profile of United States Farmworkers, 2021). The average annual income for a farmworker is less than $20,000 a year and one third of farmworkers have family incomes below the poverty line (Findings from the National Agricultural Workers Survey (NAWS) 2017–2018: A Demographic and Employment Profile of United States Farmworkers, 2021). In the state of Washington, pesticides and pesticide metabolites were detected in 85% of farmworker homes and these same chemicals were detected in the urine of 88% of the young children living in these homes (C. L. Curl et al., 2002). In fact, house dust samples collected from families of Hispanic farmworkers had anywhere from 1.8 to 9.8 fold higher pesticide residues compared to house dust collected from Hispanic non-farmworker households (Smith et al., 2017). Thus, the occupational risk of pesticide inhalation for agricultural workers is amplified by risk of pesticide inhalation within their homes. These data suggest that the health risks associated with elevated pesticide exposures in agricultural workers extend to their family members as well.

Through environmental monitoring of air, dust, and other surfaces, it is known that members of marginalized communities and agricultural workers are exposed to pesticides through inhalation (Donley et al., 2022; Lu et al., 2013). Further, biomonitoring literature indicate that non-Hispanic Blacks and Mexican Americans in the US tend to have higher average urinary and blood levels of many pesticides compared to the general population (Donley et al., 2022). A study of racial disparities in chemical biomarker concentrations found that biomarkers of pesticide exposure showed the greatest disparity between White women and women of color in the US (Nguyen et al., 2020). A study quantifying pesticide biomarkers in the breast adipose tissue of women from Long Island, New York found that the adipose tissue of Black women contained 10% more biomarkers than the adipose tissue of White women (Muscat et al., 2003). Another study reported higher levels of pesticides in the blood and urine of non-Hispanic Black women compared to non-Hispanic White women and the specific pesticides that they identified showed positive breast cancer associated biological activity in vitro (Polemi et al., 2021) (Table 1). In addition to evidence that marginalized women are disproportionately exposed to pesticides, emerging evidence supports the notion that pesticides are able to pass the placental barrier and pesticide exposures are associated with adverse pregnancy outcomes (Acosta-Maldonado et al., 2009). Pesticides have also been detected in 83% of umbilical cord samples from pregnant African American and Dominican women in New York City and pesticide exposures in Black women have been negatively associated with fetal growth and decreased infant size at birth (Harley et al., 2016; Perera et al., 2003; Whyatt et al., 2003, 2004) (Table 2).

Hispanic and Haitian female farmworkers in Florida had significantly higher levels of pesticide metabolites in their urine compared to the national averages reported in the Disease Control and Prevention National Health and Nutrition Examination Survey (NHANES) (Runkle et al., 2013). A study conducted in Idaho reported that pesticide metabolites were detected in the urine of all Latina/Latino farmworkers and many of these metabolites persisted after the spraying season was over (C. Curl et al., 2019). In Latina women in California, occupational exposure to certain pesticides was associated with increased risk of breast cancer (Mills et al., 2019). In a cohort of low-income, Latina women living in an agricultural community of California, in utero pesticide exposure was associated with decreased gestational duration (Eskenazi et al., 2004).

9. Electronic nicotine delivery systems

Electronic nicotine delivery systems (ENDS), such as e-cigarettes and vaporizers, heat nicotine, propylene glycol, vegetable glycerin, flavorings, and other chemicals to form an aerosol for inhalation (Cunningham et al., 2020). Aerosols from ENDS contains a number of chemicals, including polycyclic aromatic hydrocarbons (naphthalene, anthracene, and pyrene) and carbonyls (formaldehyde and acetone) (Cunningham et al., 2020). According to the 2020 National Health Interview Survey, 4.7% of adults 18+ years of age in the US reported current e-cigarette use (Adjaye-Gbewonyo & Boersma, 2022). Although different published papers have found that marginalized groups have higher rates of tobacco smoking and greater difficulty quitting than non-marginalized groups (Hiscock et al., 2012; Potter et al., 2020), and the relationship between cigarette smoking and fertility in males and females has been well studied (Augood et al., 1998; Dechanet et al., 2011; Kovac et al., 2015), considerably less is known about the effects of ENDS on reproductive parameters.

ENDS are often perceived as a safer alternative to cigarette smoking and a useful aid for smoking cessation (Bowker et al., 2018; Wagner et al., 2017). However, epidemiological studies suggest ENDS are detrimental to reproductive health (Cardenas et al., 2019, 2020; El-Shahawy et al., 2022; Harlow et al., 2021; Holmboe et al., 2020; S. Kim & Oancea, 2020; X. Wang et al., 2020). In men, daily e-cigarette users have a 38% lower total sperm count and increased odds of experiencing erectile dysfunction compared to non-users (El-Shahawy et al., 2022; Holmboe et al., 2020). In women actively trying to become pregnant, e-cigarette use is associated with a lower fecundability rate compared to non-users (Harlow et al., 2021). E-cigarette use during pregnancy is associated with higher prevalence of small-for-gestational-age, preterm birth, and low birth weight compared to non-users (Cardenas et al., 2019, 2020; S. Kim & Oancea, 2020; Regan et al., 2021; Regan & Pereira, 2021; Shittu et al., 2022; X. Wang et al., 2020). Interestingly, e-cigarette users that quit during pregnancy have a similar risk for small-for-gestational-age, preterm birth, and low birthweight as non-users (Regan et al., 2021; Regan & Pereira, 2021; Shittu et al., 2022). These observations highlight the importance of cessation of smoking during pregnancy to prevent adverse pregnancy outcomes. Interestingly, a study in England found an association between low SES and higher rates of e-cigarette use (Kock et al., 2020), suggesting increased exposure to ENDS by marginalized groups. Although these studies suggest ENDS are reproductively toxic, more research is needed to understand the full extent of their toxicity and whether they pose a greater risk for marginalized communities.

10. Marijuana

To date, recreational marijuana use has been legalized in 19 states, Washington D.C., and Guam (Where Is Marijuana Legal?, 2023). In 2019, 48.2 million people (approximately 18% of the U.S. population) reported using marijuana at least once (2019 NSDUH Annual National Report | CBHSQ Data, n.d.). With increasing recreational use, it is critical to understand the risks associated with marijuana consumption. Human epidemiological studies investigating the effects of marijuana on reproductive health have provided conflicting data. In men, some studies report marijuana use increases serum testosterone and decreases serum FSH levels (Fantus et al., 2020; Holmboe et al., 2020; Nassan, Arvizu, Mínguez-Alarcón, Williams, et al., 2019; Shiff et al., 2021), while other studies report no change in testosterone and FSH levels with marijuana use (Cushman, 1975; Mendelson et al., 1974; Thistle et al., 2017). Similarly, marijuana use has been reported to both increase (Nassan, Arvizu, Mínguez-Alarcón, Williams, et al., 2019) and decrease (Gundersen et al., 2015) sperm concentration (Gundersen et al., 2015; Nassan, Arvizu, Mínguez-Alarcón, Williams, et al., 2019). Interestingly, marijuana use is consistently associated with abnormal sperm motility and morphology (Carroll et al., 2020; Hehemann et al., 2021; Pacey et al., 2014). Moreover, sperm from infertile men that use marijuana exhibit greater rates of aneuploidy, chromosomal abnormalities, and DNA fragmentation than sperm from non-users (Verhaeghe et al., 2020).

In couples trying to conceive, marijuana use by the male partner did not affect the fecundability or time to pregnancy compared to non-users (Kasman et al., 2018; Wise et al., 2018). In couples using Assisted Reproductive Technologies (ART) to conceive, male marijuana use was reported to increase the probability of experiencing a live birth/100 cycles of ART compared to couples in which neither partner uses marijuana (Nassan, Arvizu, Mínguez-Alarcón, Gaskins, et al., 2019). However, moderate to heavy marijuana use in males undergoing ART was associated with a 15-23% decrease in infant birth weight compared to non-users (Klonoff-Cohen et al., 2006). Together, these data suggest that while male marijuana use may not deter a couple’s ability to conceive, it may have deleterious effects on infant health and development.

In women, relatively little is known about the effects of marijuana use on oocyte quality or cyclicity. Existing data suggest that marijuana exposure is associated with increased time spent in the follicular phase of the ovarian cycle, decreased plasma LH levels, and increased incidence of ovulatory abnormalities (Jukic et al., 2007; Mendelson et al., 1986; Mueller et al., 1990). The vast majority of available data pertain to the effects of marijuana on pregnancy and neonatal outcomes are not always consistent (Kasman et al., 2018; Mumford et al., 2021; Wise et al., 2018). Marijuana use in women trying to conceive has been associated with both reduced (Mumford et al., 2021) and unchanged fecundability (Kasman et al., 2018; Wise et al., 2018). Continued marijuana use during pregnancy was associated with adverse neonatal outcomes, including preterm birth, lower birth weight, and lower gestational age at birth compared to non-users (Corsi et al., 2019; Grzeskowiak et al., 2020). When neonatal outcomes were stratified by race, marijuana use in pregnant Black women was associated with low birth weight and small-for-gestational-age, whereas use in pregnant Hispanic women was associated with higher risk of preterm birth and infant mortality compared to non-users (Shi et al., 2021). Conversely, one study reported no association between marijuana use and preterm birth, low birthweight, fetal growth restriction, and maternal pregnancy-related hypertension, compared to non-users (Chabarria et al., 2016).

In couples undergoing ART, current marijuana use in women does not appear to affect implantation rate or pregnancy rate assessed in the first trimester (Har-Gil et al., 2021). However, when pregnancy was assessed at 24 weeks, marijuana users that conceived using ART had a 54% probability of pregnancy loss compared to 26% in non-users (Nassan, Arvizu, Mínguez-Alarcón, Gaskins, et al., 2019). Moreover, children from women undergoing ART who reported moderate to heavy lifetime marijuana use had a 17-27% decrease in birth weight compared to children born from non-users (Klonoff-Cohen et al., 2006).

It is difficult to assess the reproductive toxicity of marijuana based on the available studies in males and females due to the variability in observations between studies. This variability could be due to several reasons. First, many of these studies rely on self-reporting of marijuana use. Given social stigma and legality, it is possible that marijuana use is being underreported. Second, many studies do not stratify their data based on frequency of marijuana usage. It is possible that marijuana may have a more profound effect in chronic versus acute users. Third, as marijuana becomes legal in various states, it has become available in different forms in addition to the traditional leaves, including waxes, extracts, tinctures, teas, and edibles. Many studies do not include data on the forms of marijuana being consumed, and some forms may have more profound effects on fertility than others. Finally, while data exist suggesting marijuana use may affect neonatal outcome in Black and Hispanic communities disproportionately (Shi et al., 2021), more work is needed to assess how marijuana use affects paternal and maternal reproductive health and fertility in these communities.

11. Phthalates

Plasticizers are used in many consumer products and are added to promote plasticity, flexibility, and processability to plastics. Phthalates can be absorbed via inhalation, dermal absorption, parental administration, and ingestion (National Research Council (US) Committee on the Health Risks of Phthalates, 2008). Phthalates are known endocrine-disrupting chemicals that are associated with negative reproductive outcomes in men, women, and children (Meeker & Ferguson, 2014). They are noncovalently bound and can leach out from phthalate-containing items into food, beverages, air, dust, sediment, water, and soil, leading to widespread human exposure (Genuis et al., 2012; Kavlock et al., 2002). Although studies have indicated that phthalates have multiple routes of exposure, research on all mechanisms of phthalate exposure has not been conducted in detail. One of the least studied routes of phthalate exposure is inhalation. Additionally, studies have shown that exposure to phthalates is not proportional across populations (James-Todd et al., 2016), and that marginalized groups are exposed to higher concentrations of phthalates than the general population (James-Todd et al., 2017).

Phthalates are found in indoor and outdoor air samples (Başaran et al., 2020). In one study, nine different phthalates, all ranging from 143-2600 ng/m³, were detected in air samples collected from offices, laboratories, schools, salons, public places, and homes (Tran & Kannan, 2015). In the United States, the most dominant route of exposure in infants to di-iso-butyl phthalate (DiBP) was inhalation (Guo & Kannan, 2011). However, few studies have assessed the reproductive effects of phthalates exposed via inhalation. Thus, most of what is known about the effects of phthalate exposure on health outcomes is derived from animal studies using different exposure routes (Oudir et al., 2018) (Liu et al., 2021).

In a study conducted in Sweden, pregnant women (ranging from 3-27 weeks of pregnancy) were selected as participants, and dust was collected from their homes to measure residential indoor exposure to phthalates (Preece et al., 2021). The results indicated the presence of five phthalate diesters; di-ethyl phthalate (DEP), di-n-butyl phthalate (DnBP), DiBP, butyl-benzyl phthalate (BBzP), and di-ethyl-hexyl phthalate (DEHP) in 90% of the samples (Preece et al., 2021). DnBP was found to have the highest detection rate in residential dust at 97.4%. Intake from the residential indoor environment represented 12% of DEP and 28% of DnBP and DiBP total intakes (Preece et al., 2021). This suggests that indoor air environments contribute substantially to the total intake of DEP, DnBP, DBP, and DiBP in pregnant women. This is of concern because research has shown that prenatal exposure to phthalate mixtures can alter important processes regulated by the ovaries and testis in female and male mice, respectively (Barakat et al., 2019; Gill et al., 2021). Data also suggest that limiting phthalate-containing building materials would reduce the intake and health risk of their offspring (Preece et al., 2021).

Other studies measured urinary metabolites of phthalates in a population of pregnant woman recruited from the Medical University of South Carolina and found that non-Hispanic Black women had significantly higher amounts of urinary phthalate metabolites than White women (Bloom et al., 2019; Wenzel et al., 2018). Studies also showed that greater amounts of gestational urinary phthalates were associated with poorer birth outcomes and that the outcome varied by maternal race and infant sex (Bloom et al., 2019). Age, body mass index, education, and income were also significantly associated with phthalate concentrations in African American women (Bloom et al., 2019; Wenzel et al., 2018). A similar study measured the amounts of urinary phthalate metabolites in a population of White, non-Hispanic Black, and Hispanic pregnant women across pregnancy (8-10 weeks, 16-18 weeks, 22-26 weeks and 33-35 weeks) (James-Todd et al., 2017). The results indicated that non-Hispanic Blacks and Hispanics were exposed to higher levels of specific phthalates than Whites (James-Todd et al., 2017). Among non-Hispanic Blacks and Hispanics, concentrations of mono-n-butyl phthalate, mono-ethyl phthalate (MEP), mono-isobutyl phthalate (MiBP), mono-benzyl phthalate (MBzP) were significantly higher than in non-Whites (James-Todd et al., 2017) (Table 1). These findings highlight the importance of studying the reproductive effects of phthalate exposure via inhalation and a higher risk of exposure amongst those in marginalized communities

Collectively, phthalates are known reproductive toxicants that can interfere with the male and female reproductive system during all stages of reproductive development in animal models (Martino-Andrade & Chahoud, 2010). Epidemiologic studies also suggest that pregnant women are at higher risk of phthalate exposure due to race, ethnic background, age, body mass index, education, and income (James-Todd et al., 2016, 2017). However, limited information exists about how phthalate exposure impacts reproductive outcomes in marginalized communities, indicating a need for research focusing on phthalate exposures and marginalized communities. Studying the short- and long-term effects associated with phthalate exposure via inhalation will help address key concerns related to marginalized communities and disease burden within males and females.

12. Conclusions

Increased air pollutant exposure in marginalized communities has been documented, as evidenced by epidemiological/human studies showing higher markers of exposure in marginalized groups compared to non-marginalized populations (Table 1). Importantly, epidemiological studies have shown associations between air pollutant exposure and adverse reproductive outcomes (Figure 2). However, limited information is available regarding associations between air pollutant exposure and adverse reproductive outcomes in marginalized communities. The data presented here show that some air pollutants increase the risk of adverse reproductive outcomes in marginalized groups compared to non-marginalized populations (Table 2). For other air pollutants, limited information exists due to the lack of studies focusing on marginalized communities and reproduction. Given the lack of information and the importance of reproduction, it is important for researchers in the inhalation toxicology, reproduction, and epidemiology fields to work together in assessing and mitigating the effects of air pollutants on reproductive outcomes in marginalized communities. Urgent policies are needed to alleviate disparities in air pollutant exposure in marginalized communities and to achieve environmental justice and fair treatment, giving marginalized communities the same degree of protection as non-marginalized communities, decreasing their exposure to air pollutants and, therefore, decreasing the risk of adverse reproductive outcomes related to air pollutant exposure.

Figure 2. High exposure to air pollutants may lead to higher reproductive effects in marginalized communities compared to the general population.

Marginalized communities are disproportionately exposed to higher levels of air pollutants than the general population, increasing their likelihood of developing adverse reproductive outcomes.

Data availability

Not applicable because this is a review manuscript.