Early sex-dependent differences in response to environmental stress

Abstract

Developmental plasticity enables the appearance of long-term effects in offspring caused by exposure to environmental stressors during embryonic and foetal life. These long-term effects can be traced to pre-and post-implantation development, and in both cases, the effects are usually sex specific. During preimplantation development, male and female embryos exhibit an extensive transcriptional dimorphism mainly driven by incomplete X chromosome inactivation. These early developmental stages are crucial for the establishment of epigenetic marks that will be conserved throughout development, making it a particularly susceptible period for the appearance of long-term epigenetic-based phenotypes. Later in development, gonadal formation generates hormonal differences between the sexes, and male and female placentae exhibit different responses to environmental stressors. The maternal environment, including hormones and environmental insults during pregnancy, contributes to sex-specific placental development that controls genetic and epigenetic programming during foetal development, regulating sex-specific differences, including sex-specific epigenetic responses to environmental hazards, leading to long-term effects. This review summarizes several human and animal studies examining sex-specific responses to environmental stressors during both the periconception period (caused by differences in sex chromosome dosage) and placental development (caused by both sex chromosomes and hormones). The identification of relevant sex-dependent trajectories caused by sex chromosomes and/or sex hormones is essential to define diagnostic markers and prevention/intervention protocols.Reproduction (2018) 155 R39-R51

Elevated maternal linoleic acid reduces circulating leptin concentrations, cholesterol levels and male fetal survival in a rat model

“…In developmental programming, early life exposure to maternal perturbations can lead to an increased risk of deleterious developmental consequences, and males are at a relatively greater risk of negative effects than females (Perez‐Cerezales et al . ). This greater susceptibility of males to deleterious in utero effects may account for the decreased number of male offspring.…”

Risk factors for postdischarge growth retardation among very-low-birth-weight infants: A nationwide registry study in Taiwan

“…29 Early sex-dependent differences in response to environmental stress caused by sex chromosomes or hormones was suggested by several human and animal studies. 30 Nutrition could affect male infants more dramatically than female infants. 28 Hack et al also reported female VLBW infants had greater catch-up growth than male infants by 20 years old.…”

Sex Differences in Early Embryogenesis: Inter‐Chromosomal Regulation Sets the Stage for Sex‐Biased Gene Networks

“…[72] In fact, many diseases with early developmental origins display sex biases. [73,74] Studies in rodent, bovine, and human blastocysts have shown that the response to environmental conditions is different in male and female embryos, [75,76] reflecting differences in their metabolism. [41,72] Also, there are evocative reports of sex-specific signaling by the embryo to the mother.…”