Sex-specific differences and developmental programming for diseases in later life

Abstract

Epidemiological data indicate that developmental programming of various non-communicable diseases (NCDs) occurs as a consequence of altered maternal metabolic and physiological status due to a number of environmental insults during pregnancy. Sex-specific differences have also been reported in most NCDs. Evidence suggests that beginning from conception, the maternal and neonatal metabolic environment, including hormones, contributes to sex-specific placental development. The placenta then regulates the sex-specific differences in NCDs via the epigenetic mechanisms that are further affected by hormones. Male and female embryos have been reported to exhibit sex-specific transcriptional regulation, and it is suggested that their development can be considered as separate processes beginning from conception. This review summarises various animal and human studies examining sex-specific differences in NCDs due to differential placental epigenetic developmental programming. An overview of possible mechanisms underlying this is also discussed. Further, the review describes sex-specific changes in the structure and function of the placenta in pregnancies complicated by fetal growth restriction, pre-eclampsia and preterm birth. Thus, because sex-specific differences are associated with fetal outcome and survival, future studies need to take into consideration the sex of the fetus while explaining the concept of the developmental origins of health and disease.

Gestational intermittent hypoxia induces endothelial dysfunction, reduces perivascular adiponectin and causes epigenetic changes in adult male offspring

“…Sex‐dependent differences can arise from the model used, with male offspring being more vulnerable to maternal insults (Sundrani et al . ; Dearden et al . ).…”

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

“…[74] The derivation of ES cells has facilitated studies on how humans differ from animal models. For obvious reasons, research on human embryos is difficult and usually of low power.…”

Early sex-dependent differences in response to environmental stress

“…From the early stages of development, the foetus is very susceptible to steroid hormone exposure, which plays important roles in tissue and organ differentiation (Sundrani et al 2017). Thus, androgens have a role not only in the maturation of the male foetus but also in the development of mammary gland and folliculogenesis in the female foetus.…”

“…These observations suggest that male foetuses are less buffered than females against certain environmental insults. Thus, under various stressors, male foetuses exhibit higher late foetal mortality due to a greater in utero vulnerability (Eriksson et al 2010), and their foetal growth is more affected than that of females (Sundrani et al 2017) (Fig. 1).…”

“…Conversely, environmental conditions experienced in early life can dramatically influence neonatal and adult biology, which may result in detrimental long-term effects (Laguna-Barraza et al 2012). There are many human and animal studies demonstrating sexual differences in response to various developmental insults during periconception (Fleming et al 2015a) and pregnancy (Sundrani et al 2017) and demonstrating sexual differences in response to various developmental insults during pregnancy (Sundrani et al 2017). However, there is a gap in knowledge of the mechanism(s) mediating environmental and maternal programing of preimplantation development.…”