Table 4.

In vivo studies with plasticizers found in food

Research design	Dosage regimen	Parameters monitored	Outcomes/main conclusion of the study	References
Investigate ovarian folliculogenesis and steroidogenesis in adult female rat offspring born to mothers exposed to low doses of BPA	BPA50: 50 mg/kg day; BPA0.5: 0.5 mg/kg day	Estrous cycle; Average size of preantral and antral follicles	Folliculogenesis and steroidogenesis are targets of BPA within the ovary	[46]
Effect of a low dose of BPA on the reproductive axis of prepubertal female rats	0.1% ethanol or BPA in their drinking water	Hormone levels	LH and estradiol levels increased significantly meanwhile, FSH ones showed no significant changes. The number of primary, secondary, and atretic follicles increased and antral ones were decreased. Early exposure to a low dose of BPA disrupts the normal function of the reproductive axis in prepubertal female rats	[47]
This study had the goal to study the BPA effects on the ovaries function and structure and also to access to the levels of expression of the genes related to follicle development	10, 40, and 160 mg/kg of BPA	Serum estradiol (E2) and progesterone (P4); Rat body weights and ovary coefficients; The number of follicles at different stages; Changes in the mRNA expression of FIGLA, H1FOO, and AMH genes; Changes in protein expression of FIGLA, H1FOO, and AMH genes	This study demonstrates the probable negative role that BPA plays in ovarian development, and how the genes related to follicle development can be part of these outcomes	[57]
This study was performed to examine whether prenatal exposure to BPA analogs, BPE and BPS, negatively impacts female reproductive functions and follicular development using mice as a model	BPA, BPE or BPS (0.5, 20 or 50 µg/kg/day)	Serum levels of E2 (sensitivity 3 pg/ml) or testosterone (sensitivity 90 pg/ml)	Prenatal exposure to BPA analogs, BPE and BPS, have effects on fertility in later reproductive life probably due to the disruption of early folliculogenesis	[58]
Effects and potential mechanism of BPA on mouse ovarian follicular development and FGSCs	BPA (12.5, 25, and 50 mg/kg/day)	–	The effect of BPA on ovarian follicular development and FGSCs, especially the effect on FGSCs, suggests a novel mechanism of how BPA causes female infertility	[59]
The aim of this work was to test the effect of chronically exposed female mice to a mixture of three phthalates and two alkylphenols from conception to adulthood at environmentally relevant doses	Two doses: 1 and 10 mg/kg body weight/d of the total mixture	Plasma hormonal levels; Reproductive endpoints; Histological evaluation of the number of preantraland antral follicles; RNA extraction and real-time polymerasechain reaction; Protein extraction and Western blotting	These results indicate that not only exposure but also its level is relevant to assess the effective contribution of EDs in the development of diseases	[48]
To test whether DBP causes ovarian toxicity	DBP at 0.01, 0.1, and 1000 mg/kg/day	Estrous cyclicity; steroidogenesis; ovarian morphology; Apoptosis and steroidogenesis gene expression	A 10-day exposure to DBP disrupted reproductive processes in CD-1 mice; DBP exposure resulted in decreased circulating E2; Antral follicle numbers and apoptosis gene expression were altered at low doses; Estrous cyclicity and corpora lutea counts were altered at a high dose; DBP exposure resulted in altered steroidogenesis gene expression	[49]
Investigate the negative effects of DEHP exposure on oocyte development	DEHP (40 μg/kg body weight)	Cytoskeleton; apoptosis; ROS levels; epigenetic modifications; Protein Juno receptor	DEHP exposure reduced the maturation and fertilization capabilities of mouse oocytes by affecting cytoskeletal dynamics, oxidative stress, early apoptosis, meiotic spindle morphology, mitochondria, ATP content, Juno expression, DNA damage, and epigenetic modifications in mouse oocytes	[50]

BPA Bisphenol A, LH Luteinizing hormone, FSH Follicle-stimulating hormone, E2 17β-Estradiol, P4 Progesterone, BPE Bisphenol E, BPS Bisphenol S, FGSCs female germline stem cells, EDs Endocrine disruptors, DBP Di-n-butyl phthalate, DEHP Di(2-ethylhexyl) phthalate