Transgenerational transmission of environmental effects in livestock in the age of global warming

Abstract

Recent decades provide mounting evidence for the continual increase in global temperatures, now termed “global warming,” to the point of drastic worldwide change in the climate. Climatic change is a long-term shift in temperatures and weather patterns, including increased frequency and intensity of extreme environmental events such as heat waves accompanied by extreme temperatures and high humidity. Climate change and global warming put several challenges to the livestock industry by directly affecting the animal’s production, reproduction, health, and welfare. The broad impact of global warming, and in particular heat stress, on-farm animals’ performance has been comprehensively studied. It has been estimated that the US livestock industry’s loss caused by heat stress is up to $2.4 billion annually. However, the long-term intergenerational and transgenerational effects of climatic change and global warming on farm animals are sparse. Transgenerational effects, which are mediated by epigenetic mechanisms, can affect the animal’s performance regardless of its immediate environment by altering its phenotypic expression to fit its ancestors’ environment. In many animal species, environmental effects are epigenetically encoded within a narrow time interval during the organism’s gametogenesis, and these epigenetic modifications can then be intergenerationally transmitted. Several epigenetic mechanisms mediate intergenerational transmission of environmental effects, typically in a parent-dependent manner. Therefore, exposure of the animal to an extreme climatic event and other environmental stressors during gametogenesis can undergo epigenetic stabilization in the germline and be passed to the offspring. As a result, the offspring might express a phenotype adjusted to fit the stressors experienced by their ancestors, regardless of their direct environment. The purpose of this perspective is to review current evidence for intergenerational and transgenerational transmission of environmental stress effects, specifically in the context of global warming and climate change, and to offer viewpoints on the possible impacts on the livestock industry.

Introduction

The livestock industry is key in supplying the worldwide nutritional demands, which are expected to rise with the increase in the global population. At the same time, the livestock industry is expected to be adversely affected by global warming and climate change in various aspects (Thornton 2010). As a result, livestock-based food security will (and already) experience limitations in many countries that lack technical and economic resources to mitigate climate change impacts (Godber and Wall 2014). The term “global warming” herein refers to the long-term heating of the global surface and ocean observed for more than a century due to human activities and increases in heat-trapping greenhouse gas levels in the atmosphere. The current process of global warming, in turn, drives climate change, which is a long-term change in the temperatures and weather patterns that define regional and global climates (Zandalinas et al. 2021). Climate change is expected to affect livestock production because of alterations in the availability of natural resources, feed resources, quality and quantity of water, diseases, and the increased prevalence of heat stress conditions (Garnett 2009). Accordingly, climate change is likely to expose farm animals to various stressors and physiological challenges. Global warming is expected to affect directly and indirectly the livestock industry. It is likely to affect crop variety and reduce diversity, quality, and quantity. This can lead to recurrent variations in the animals’ diets and the ability to provide them with their nutritional needs (Rojas-Downing et al. 2017). Global warming can also change pathogens’ diversity, spread vectors, food-borne diseases, and host resistance, leading to increased animal morbidity and mortality and impacting global food security (World Bank 2008; Thornton et al. 2009; Nardone et al. 2010).

Extreme temperatures (high and low) are among the characteristics of climate change and are expected to challenge animal thermoregulation. The animal thermal comfort zone is a range that combines ambient temperature, relative humidity, and additional environmental factors, where the individual can exhibit the most efficient performance with minimal energy spending (Ames 1980; Nardone et al. 2006). Upon deviation from this zone, the animals will suffer from thermal stress, which requires more energy to maintain thermoregulation following a decreased efficiency in production processes (Bianca 1976). Heat stress is a private case of thermal stress. It is defined as the sum of environmental factors (e.g., ambient temperature, humidity, and radiation) that cause an increase in the animal’s body temperature and induce a physiological response (Dikmen and Hansen 2009). Heat stress has been found to have an overall negative effect on livestock. For instance, in ruminants, heat stress reduces fertility and embryonic survival in cattle. In late gestation, it attenuates fetal growth and alters the endocrine status of the dam. Heat stress effects during late pregnancy are also affecting postpartum lactation and reproduction. In lactating cattle, heat stress significantly reduces food intake and rumination with wide-ranging physiological and metabolic impacts (Collier et al. 1982). The immune system and the immune response of livestock are negatively affected by heat stress. Livestock becomes more susceptible to diseases, and the incidence of several diseases increases with an increase in the mortality rate (Chirico et al. 1997; Mashaly et al. 2004; Dahl et al. 2020). In addition, heat stress was reported to alter the animal microbiota and, consequently, the animal metabolic pathways (Wang et al. 2018; Zhu et al. 2019). Apart from the attention recently given to the direct effects of climatic change and global warming on the livestock industry and the animals’ physiological responses to the changing environment, few works have demonstrated livestock adaptation to an extreme climate on an evolutionary scale. For instance, Buggiotti et al. found an adaptive missense variant in the highly conserved NRAP gene in the Yakut cattle. Since this amino acid substitution is shared among at least 16 species of cold-adapted mammals, the authors suggested a convergent evolution event and fast fixation in the Yakut population to adapt to the extreme climate (Buggiotti et al. 2021). However, so far, less attention has been given to the transgenerational effects due to global warming and climate change on livestock production, physiology, and adaptation.

Transgenerational effects are observed effects on the organism that cannot be attributed to genetics or environmental effects directly experienced by the individual. For example, environmental stress can directly affect the embryo in utero and its developing oocytes in the female embryos. Therefore, an altered phenotype in the third generation after exposure to environmental stress could be attributed to transgenerational inheritance. Consequently, in female transmission, the F3 generation is the first generation not directly exposed to this factor (Heard and Martienssen 2014). The shorter timescale of phenotypic effects can be described as intergenerational, although they might share similar molecular mechanisms as transgenerational effects (Perez and Lehner 2019).

The first observation of possible adverse transgenerational effects due to a mismatch between parent-offspring environments was described more than a century ago. In the “Science” issue of September 2009, Elizabeth Pennisi revived the story of Paul Kammerer and his controversial midwife toad experiment from the early twentieth century (Elizabeth 2009). Contrary to most frogs that lay their eggs in aquatic environments, midwife toad mate on dry land, and the male carries the eggs until the embryos emerge as tadpoles. Upon forcing the toads to mate and lay eggs in a wet environment, Kammerer reports that the resulting offspring expressed several new traits commonly seen in an aquatic environment. Kammerer reported these aqueous phenotypes persist for several generations and pass through the paternal lineage (Elizabeth 2009). The discovery of epigenetic inheritance and its related mechanisms in the late twentieth century allowed a re-evaluation of the midwife study by Alexander Vargas that pointed out various features corresponding to epigenetic inheritance (Vargas 2009). Apparently, the exposure of the toads to an extreme environment caused a phenotypic shift in the progenies that was passed for several generations regardless of their natural environments to fit their ancestor environment better, likely by epigenetic inheritance.

Epigenetic inheritance is the transmission of environmental information through generations by epigenetic markers that affect the offspring’s phenotype without altering the DNA sequence. The epigenetic markers lead to phenotypic shifts by modifying the gene expression pattern (Heard and Martienssen 2014). Several epigenetic mechanisms enable the encoding and transgenerational transmission of environmental information in animals. Among them are DNA methylation, histone modifications, and noncoding RNA. DNA methylation in vertebrates involves the addition of a methyl group, primarily at CpG dinucleotides, by DNA methyltransferases. Methylated CpG sites in the enhancer and promoter regions of genes typically repress gene expression, whereas methylated CpG sites in the gene body will likely lead to enhanced gene expression (Kumar et al. 2018; Greenberg and Bourc’his 2019). Histone modifications refer to a group of post-translational modifications of the histones, the proteins that pack the genomic DNA, like methylation or acetylation of the histone lysine residues. These chemical modifications can alter the histones’ properties, leading to chromatin remodeling and consequently changing the gene expression mode (Bártová et al. 2008). Noncoding RNAs are transcripts that are not translated into proteins and are usually subdivided according to length. Because of their capability to directly bound to proteins, DNA, and RNA sequences, noncoding RNAs can regulate epigenetic modifications and gene expression in the chromatin, transcriptional and post-transcriptional levels. For instance, by binding to a specific mRNA, short noncoding RNAs can induce its degradation or attenuate its translation (Collins et al. 2010). In animals, the epigenetic encoding of parental environmental information takes place mainly during gametes and embryo development once epigenetic reprogramming occurs (Tsankova et al. 2007; Reik 2007; Messerschmidt et al. 2014). Thus, epigenetic information that escapes the reprogramming waves during gametogenesis and after fertilization can potentially transmit environmental information (Seisenberger et al. 2013). Indeed, a such phenomenon of a stably inherited alteration in the epigenetic code by modification of DNA methylation in the germ line after exposure to environmental stimuli has been shown previously to be maintained for several generations (Nilsson et al. 2018).

Currently, there is considerable evidence that the offspring may epigenetically inherit such adaptability to better cope with extreme environmental conditions and potential stressors (Wang et al. 2017; Amiri and Bandani 2021). However, what are the expected consequences in the case of a mismatch between the parent-offspring environment, and how will it affect the progenies’ performances? Since, as described above, global warming leads to a less stable environment with more fluctuation between generations, exposure of the animal to extreme conditions during the interval of epigenetic reprogramming may cause adverse effects on its progenies. The purpose of this perspective is to review some of the current knowledge on the transgenerational transmission and epigenetic inheritance of environmental effects and to argue that climate change, global warming, and increased episodes of extreme climatic events like heat stress conditions may have a long-term transgenerational impact that should be taken into account in animal farming.

Epigenetic inter-and-transgenerational inheritance in human and animals

Most evidence for epigenetic inheritance as a result of exposure to environmental stimuli comes from humans and model organisms. Data that have been collected in the frame of the Överkalix cohorts in northmost Sweden revealed an association between grandparents’ access to food and their probands health condition and longevity. First, an effect of food availability just before the paternal grandfather’s puberty (that is, during the male gametogenesis) on the probands’ longevity was observed. It has been found that insufficient access to food before the grandfather’s puberty was significantly associated with the increased longevity of the grandchildren. In contrast, food abundance was associated with a significantly reduced life span (Bygren et al. 2001). Later on, Kaati et al. found that poor availability of food just before the father’s puberty reduced mortality due to cardiovascular diseases (Kaati et al. 2002). They also observed a remarkable impact on the grandchildren’s diabetes-related mortality. If the paternal grandfather was exposed to an excess of food before puberty, the proband had significant elevation mortality related to diabetes. However, the father’s exposure to a surfeit of food just before puberty tended to protect the proband from diabetes (Kaati et al. 2002). Accordingly, this suggests that ancestors’ exposure to a more extreme nutritional environment can negatively affect their progenies’. Nonetheless, these effects can be moderated or abolished by a tandem exposure of the next generation to a similar environment.

Another set of evidence for the transgenerational effects of exposure to an extreme nutritional environment comes from the Dutch famine cohort. The Dutch famine cohort is unique in that the population, which otherwise lived in a well-nourished environment but, due to the circumstances of World War II, was exposed to extreme starvation between the years 1944–1945. Moreover, soon after World War II, this population returned to the same environment of high food availability (De Rooij et al. 2021). Therefore, individuals exposed to starvation in the time window that allows for epigenetic encoding of the environmental information in the germ cells can “fit” the offspring to an extreme environment they will not experience. Interestingly, one of the findings was that F2 offspring whose paternal grandmothers experienced starvation during gestation had higher BMIs than F2, whose paternal grandmothers did not experience undernourishment (Veenendaal et al. 2013). An additional study on the Dutch famine found that F2 offspring of starvation-exposed F1 mothers had poor health, which included a higher prevalence of atopic disease, autoimmune diseases, cancer, and acquired neurological conditions (Painter et al. 2008). A possible interpretation of these findings is that epigenetic reprogramming in starvation-exposed embryos is designed to fit offspring to a low-calorie environment, whereas the progenies lived in high food availability environment. This interpretation gained support from studies on the survivors of the siege of Leningrad (St. Petersburg).

Contrary to the Dutch famine cohort, the people of Leningrad experience persisting conditions of poor nutrition. In concordance with the above interpretation, the progenies of the survivors of the siege of Leningrad were not, or only mildly, affected by the environment their ancestors experienced (Stanner et al. 1997; Lopomo et al. 2016). Altogether, the above observation supports that a mismatch between the parent’s and their offspring’s environment might negatively affect the progenies’ adaptation.

Because of their relatively short generational time, rodents provide an opportunity to study epigenetic inheritance in mammals and large animals. In addition, rodents are a good model for paternal epigenetic inheritance since males are moved from cages shortly after mating and, therefore, almost have no contribution to the next generation’s development. Research in rodents provided evidence for epigenetic inheritance after exposure to nutritional challenges and exogenous chemicals, demonstrating the mechanistic explanation for the observation in humans as described above (Anway et al. 2005; Carone et al. 2010; Ng et al. 2010). One known case of epigenetic inheritance in mice was demonstrated on the agouti viable yellow locus. It was shown that the supplementation of methyl donors during the mother’s pregnancy modified the expression of the coat color and obesity of her progenies by down-regulation of the agouti gene via DNA methylation (Waterland and Jirtle 2003). Studies in mice also demonstrated intergenerational behavioral effects of social stress. Tamara et al. found that the offspring of males subjected to maternal separation retained depressive-like behaviors even though these males were raised under normal conditions. Moreover, these behavioral abnormalities were associated with altered DNA methylation in the promoter of several genes related to the expressed phenotype in the germline of the maternally separated males and the brain of their offspring (Franklin et al. 2010). In an additional experiment, F0 mice were subjected to odor-fear conditioning before conception. The F1 and F2 offspring had an increased sensitivity to the F0 fear-conditioned odor, and this effect was transmitted through the paternal gametes. The odors sensitivity of the F1 and F2 offspring was complemented by an increased representation of the odorant pathway and hypomethylation of the odor’s olfactory receptor (Dias and Ressler 2014). Taken together, the above example from rodents demonstrates the transgenerational transmission of environmental effects by an inherited epigenetic modification reflected in altered gene expression and offers additional evidence for the malfunction of the progenies due to their adaption to their ancestors’ environment.

Assessing transgenerational effects in livestock can be highly valuable. It can contribute to the management and interface decisions of the industry. Moreover, if environmental effects can transgenerationally affect the progenies’ phenotypes, they should be accounted for in the animal breeding programs. Furthermore, in many livestock breeding programs, only a few males sire many animals. Therefore, transgenerational epigenetic inheritance through paternal lineage can affect numerous individuals. Studies in farm animals are typically restricted to relatively small controlled cohorts and the number of analyzed generations due to the costs and long generational time compared to model organisms. Therefore, evidence from livestock mainly refers to intergenerational epigenetic inheritance in limited cohorts that experience induced environmental conditions. Several such studies investigated dietary effects on economic and health traits in livestock. For instance, under a high-zinc maternal diet, chicks’ offspring had an anti-inflammatory response through epigenetic modifications of the anti-inflammatory A20 gene promoter (Li et al. 2015). Intergenerational effects of behavioral stress were also tested in chickens. First, previous studies demonstrated that upon exposure to a stressful environment during early life, chickens present resiliency later in life upon reexposure, compared to untreated chickens. This pre-adaptation was shown to be regulated by a decline in the corticotrophin-releasing hormone gene expression that was mediated by epigenetic modification in the gene intron in the hypothalamic paraventricular nucleus somatic tissue (Cramer et al. 2015, 2019). The transgenerational transmission of behavioral stress was demonstrated in a study by Lindqvist et al., where the researchers tested the effect of a stressful environment on the behavior of domesticated and undomesticated species of chickens and their progenies. They found that the offspring of the stressed domestic chickens had reduced spatial learning ability, were more competitive, and grew faster than the offspring of non-stressed animals. The behavioral alterations were associated with similar differential gene expression observed in the treated parents and their offspring compared to the untreated animals, which supports possible regulation of gene expression by inherited epigenetic modifications. These observations were not found for the undomesticated chickens. The authors concluded that domestication might favor the transmission of epigenetic information to control behavior modifications between generations (Lindqvist et al. 2007). A similar observation was reported for domestic chickens after their subjection to social isolation in early life. Here also, behavioral alteration and differential gene expression were found in the stressed animal and their male progenies (Goerlich et al. 2012).

Commercial dairy cattle herds in developed countries are operating breeding programs aiming to improve target traits. Breeding programs are based on intensive data recording, including extensive pedigree, phenotypic, and environmental information, which provides an opportunity to study epigenetic inheritance. Using linear mixed models from such records, Gudex et al. have shown a significant association between the prenatal environment of the dam and the grand dam on cow milk production. The similar phenotypic effects observed between F1 and F2 pointed to a likely intergenerational epigenetic inheritance (Gudex et al. 2014). Gonzalez-Recio et al. reported that calves born to lactating mothers produced less milk during adulthood and had reduced lifespans compared with their first-born calves, providing additional evidence for intergenerational transmission of the epigenetic regulation of milk production (González-Recio et al. 2012). Several studies on intergenerational epigenetic inheritance performed on cattle models offer mechanistic evidence for these observations. First, it has been demonstrated that lipid synthesis and milk production are at least partially controlled by epigenetic programming. For instance, during the lactation cycle, the bovine αS1-casein gene and the (STAT)5-binding lactation enhancer are hypomethylated (Platenburg et al. 1996; Vanselow et al. 2006). Second, upon infection and inflammation, the mentioned genomic regions become methylated with down-regulation of the αS1-casein gene expression and reduced milk production, as occurs in non-milking periods (Vanselow et al. 2006; Singh et al. 2009; Swanson et al. 2009).

More evidence for the intergenerational effect of the nutritional supplement in livestock comes from research on sheep. Sinclair et al. observed that upon limiting vitamin B12, folate, and methionine supply from the periconceptional (i.e., the period before conception and early pregnancy) diet of mature female sheep, offspring were both heavier and gained more body fat, stimulated altered immune responses to antigenic challenges, were insulin-resistant, and had elevated blood pressure, mainly in males. These intergenerational effects were accompanied by altered methylation status in the fetal liver (Sinclair et al. 2007). Other studies demonstrated the intergenerational effect of dietary restrictions during gestation on the muscle tissue composition in different developmental stages and on the global DNA methylation in the liver of the offspring (Daniel et al. 2007; Chadio et al. 2017). On the other hand, the overnutrition of pregnant sheep has led to increased subcutaneous fat mass in the postnatal lamb. At the same time, overfeeding during the periconceptional period caused an increase in total body fat mass in the female progenies. A short interval of food restriction during the periconceptional period reverses the effect of overnutrition and modifies the epigenetic status of the IGF2 gene in the progeny’s adrenal (Zhang et al. 2011). This finding locates the programming of nutritional effects in the offspring to the periconceptional period and late pregnancy.

Swine are both central in the livestock industry and used as a model for human disease research. Despite their centrality to the livestock industry and modeling human diseases, only a few studies have explored possible intergenerational and transgenerational effects. Two examples showed an association between maternal nutritional environment to epigenetic modification and phenotypic alteration in their progenies (Liu et al. 2011; Altmann et al. 2012). In addition, daily maternal supplementation with methyl donors from conception and during gestation was associated with increased methylation of IGF1 and SLC15A1 genes in the liver and small intestine of the offspring, respectively (Liu et al. 2017; Jin et al. 2018). A three-generation study has provided one of the very few pieces of evidence for transgenerational epigenetic inheritance in livestock. Male boars were supplemented with high amounts of methylating micronutrients. Their F2 pigs have lower fat percentages and differ in several carcass traits compared to the control group. The differences in the carcass traits were accompanied by broad differences in methylation and expression status of lipid metabolism genes (Braunschweig et al. 2012).

Epigenetic inheritance of heat stress effects in lab and farm animals

Despite substantial evidence for inherited epigenetic reprogramming due to environmental stressors in various species, studies on the trans- and intergenerational heat stress effects in mammals and large animals are limited. Because extensive epigenetic reprogramming occurs during early embryo development and the preimplantation embryos are highly vulnerable to heat stress, considerable attention was given to studying epigenetic modification due to heat stress in embryos (de Barros and Paula-Lopes 2018). As described above, gametogenesis and early embryo development are critical for encoding and maintaining intergenerational epigenetic information, including the allelic status of imprinted genes. After fertilization, the paternal and maternal genomes are highly methylated; therefore, the zygote undergoes epigenetic reprogramming by global demethylation to maintain totipotency. Imprinting and inherited epigenetic information from the germline must maintain their epigenetic status during embryo development and after birth, likely by escaping demethylation after fertilization (de Barros and Paula-Lopes 2018). Various environmental effects, like heat stress, can interrupt these processes during the development of the gametes and embryo.

As an example of heat stress’s effects during mammal gametes’ development, male mice exposed to mild scrotal heat stress (i.e., the anatomical structure that holds mammal testes) were subjected to in-vitro fertilization (IVF) with oocytes of untreated females. The resulting male offspring have glucose intolerance and insulin resistance. The expression of genes involved in glucose metabolism and insulin signaling was altered in the liver of this male offspring. In addition, the observed differential gene expression was accompanied by altered methylation in the fathers’ sperm and their male offspring’s liver (Wan et al. 2020). This suggests that the exposure of the male germline cells to heat stress conditions has led to epigenetic reprogramming in the sperm cells that later was observed in the offspring somatic tissue together with phenotypic malfunction.

Zhu et al. found that upon heat stress, paternal but not maternal imprinted genes in mice embryos had reduced methylation than in control, suggesting a parental-dependent gene-specific epigenetic heat stress effect (Zhu et al. 2008). In chicks, maternal heat stress resulted in the upregulation of heat shock proteins, the response to oxidative damage, and apoptosis in the embryonic heart. These alterations were associated with global epigenetic modification in the embryonic heart (Vinoth et al. 2018). Heat stress response in the embryo was shown to be mediated by heat-induced oxidative stress and elevated ROS production (Sakatani et al. 2004; Ortega et al. 2016). Interestingly, maternal dietary supplementation of antioxidants eliminated the heat stress effect observed on the embryo via epigenetic regulation (Zhu et al. 2008). Likewise, a positive long-term effect of thermal conditioning during chick embryogenesis in their adulthood was previously observed. The authors reported a postnatal thermotolerance capacity to heat challenge upon induction of heat stress during embryo development. The observed phenotypic adjustment was controlled by elevated heat shock proteins (HSP) promoter activity, reflected in its hypomethylation and higher HSP gene expression (Vinoth et al. 2018). Thus, demonstrating that epigenetic transmission of the embryonic thermal environment information improves the organism’s fitness in adulthood upon recurrence exposure to the thermal stressor.

The direct effects of heat stress on dairy cattle were comprehensively studied. The ambient temperature can directly affect dairy cows’ health, reproduction, and productivity. For instance, prolonged heat stress accounts for up to 25% loss in milk production (Collier et al. 2006). In addition, an apparent seasonal effect on conception rate (CR) over the last two decades was inspected in the Israeli dairy cattle herd, with an almost twice-higher CR during the winter compared to the summer. Strikingly, an average elevation of 1.5 °C has led to an additional decrease of 5% in the CR (Wolfenson and Roth 2019). Furthermore, studies showed that the elevation in the thermal humidity measurements above the thresholds of heat stress conditions causes a significant acceleration in the death rate (Collier et al. 2019).

Despite the overall physiological effects of direct exposure to heat stress in dairy cattle, until recently, the long-term intergenerational effects were not demonstrated. A recent experiment compared the performances of the F1 heifer that was born to heat-stressed cows during late pregnancy to that of cooled cows. The authors reported that heat stress during late gestation negatively affects survival and milk production in F1 offspring (Monteiro et al. 2016). A later study demonstrated that impaired milk production in the progenies of the heat-stressed dam is associated with aberrant mammary morphology (Skibiel et al. 2018). Continued research across ten consecutive years in Florida was the first to test the intergenerational transmission of the effects of heat stress during late gestation on both the F1 and F2 progenies. F1 milk production and survival rate were reduced compared with F1 progenies of cooled dams. Similar trends were observed for the F2 granddaughters until their first lactation. An economic evaluation estimated a significant loss in F1 progenies production due to maternal exposure to heat stress during late pregnancy (Laporta et al. 2020).

Recently, we hypothesized that heat stress in pregnant cows might induce epigenetic modifications in the developing female embryo germ cells and, therefore, can transgenerationally affect the phenotype of the progenies up to the F3 generation. We tested our hypothesis by analyzing hundreds of thousands of cows’ phenotypic, genetic, and environmental records over four consecutive generations between 1995 and 2020. In addition, we obtained hourly temperature and humidity measurements across the last decades in Israel and scored the pregnancy periods of the F0 cows for exposure to heat stress. We then analyzed the effects of different levels of heat stress combinations during the pregnancies of F0 and F1 on their F3 cows’ performance. Providing the first evidence for transgenerational heat-stress effects in livestock through the maternal lineage, we found significant phenotypic effects in the F3 progenies of F0 pregnant dairy cows exposed to heat stress. We found the incidence of heat stress conditions during F0’s second pregnancy semester to be negatively associated with milk production, composition, and calving-associated traits of the F3 progenies (Weller et al. 2021). For F3 cows to inherit the epigenetic information encoded in the oocytes of their F1 ancestors during F0 pregnancy, the epigenetic modification must be preserved, at least partially, during the formation of the F2 gametes by either inefficient erasure or partial restoration of the gained epigenetic marks (Klosin and Lehner 2016). Thus, combinations of different environmental stimuli of the F0 and F1 cows can differentially affect the phenotype of the F3 cows. As summarized in Fig. 1, we found the combined effects of the environmental stimulations during the pregnancy of F0 and F1 cows are additive, where the effects of F1 dominate those of F1. This supports an inefficient restoration or erasure of the epigenetic marks. F0 and F1 tandem exposure to heat stress produced the most negative effect on their F3 progenies. At the same time, combinations of opposite exposure trends to heat stress moderate F3 phenotypic impact (Weller et al. 2021). We also found that the average increase in heat stress conditions over the years is mainly the product of extreme years flanked by years with more moderate values. This suggests an increased prevalence of mismatch in the parent-offspring environment. As a result, the estimated breeding value computed for each animal according to its pedigree and direct environment does not fully represent its genetic potential that is also affected by its unmatched ancestors’ environment. In addition, since the combination of different gestation periods between generations can moderate the impact of exposure to heat stress, it should be considered in the reproduction strategy in livestock herds (Weller et al. 2021).

Fig. 1.

Graphic summary of the findings from (Weller et al. 2021). a A schematic representation of the experimental design of four consecutive generations. First, the exposure of the F0 and F1 generation to heat stress conditions during pregnancy was determined. Then, the associated performances for a panel of traits of the F2 and F3 generation were analyzed. b Illustration of the results for transgenerational effects for F3 productive traits (i.e., fat, protein, and milk production). The performances of the F3 cow are denoted in milk bottles as a function of different combinations of exposure of the F0 and F1 ancestors to heat stress during the second-semester pregnancy. The sun symbolizes exposure to high incidence of heat stress conditions, and the cloud denotes low or no exposure to heat stress during pregnancy. Weller et al. reported transgenerational heat stress effects are additive, and tandem exposures of the F0 and F1 cows to heat stress during late gestation have the most negative impact (right panel) on the F3 production traits. Opposing trends between the F0 and the F1 exposures to heat stress were found to moderate the negative or positive effects on the F3 performances. The effect of F1 generation was noted to dominate over F0

Summary

Among the effects of global warming and climate change is annual and seasonal environmental fluctuation with extreme climatic events, as summarized in (R.K Pachauri 2015). Therefore, short- and long-term livestock adaptation and mitigation become more challenging, as the environmental conditions across generations can be highly varied. As described herein, global warming is expected to expose farm animals to various stressors due to a higher incidence of heat stress conditions, the alteration in nutritional composition and availability, and the introduction of divers and new pathogens (Rojas-Downing et al. 2017). All these stressors have been demonstrated to modify epigenetic programming in the animal germ cells to allow the progenies to adapt to their ancestors’ environment. The mismatch between stressors experienced by the ancestor in the narrow time interval of epigenetic reprogramming to the environment experienced by its offspring can negatively affect their production, reproduction, and health. Therefore, to moderate the adverse effects, special attention should be given to the care of farm animals, especially during periods when epigenetic mechanisms encode environmental effects in the germ cells that will give rise to the next generations. For instance, these can be achieved by improving cooling technologies, with particular emphasis on cooling during the pregnancy of female and male puberty. Additional improvement could be attained by adjusting the animal diet during the most vulnerable gametes and embryo development periods.

Furthermore, accounting for epigenetic inheritance in the reproduction and breeding program can moderate adverse effects, and better estimate the animal’s genetic value. Because of the breeding strategy in livestock herds, which is usually based on a small number of males siring numerous animals, adverse effects on one individual may affect a large portion of the population. On the other hand, special attention to the small population of sires will effectively allow for moderating and controlling negative effects on the entire population.

Declarations

Competing interests

The author declares no competing interests.