The gestational foundation of sex differences in development and vulnerability

Abstract

Despite long-standing interest in the role of sex on human development, the functional consequences of fetal sex on early development are not well understood. Here we explore the gestational origins of sex as a moderator of development. In accordance with the focus of this special issue, we examine evidence for a sex differential in vulnerability to prenatal and perinatal risks. Exposures evaluated include those present in the external environment (e.g., lead, pesticides), those introduced by maternal behaviors (e.g., alcohol, opioid use), and those resulting from an adverse intrauterine environment (e.g., preterm birth). We also provide current knowledge on the degree to which sex differences in fetal neurobehavioral development (i.e., cardiac and motor patterns) are present prior to birth. Also considered are contemporaneous and persistent sex of fetus effects on the pregnant woman. Converging evidence confirms that infant and early childhood developmental outcomes of male fetuses exposed to prenatal and perinatal adversities are more highly impaired than those of female fetuses. In certain circumstances, male fetuses are both more frequently exposed to early adversities and more affected by them when exposed than are female fetuses. The mechanisms through which biological sex imparts vulnerability or protection on the developing nervous system are largely unknown. We consider models that implicate variation in maturation, placental functioning, and the neuroendocrine milieu as potential contributors. Many studies use sex as a control variable, some analyze and report main effects for sex, but those that report interaction terms for sex are scare. As a result, the true scope of sex differences in vulnerability is unknown.

PCBs and measures of attention and impulsivity on a continuous performance task of young adults

“…As discussed earlier, these findings have limited and inconsistent support in the PCB literature. Our findings are, however, consistent with the conclusions of DiPietro and Voegtline (2015) who comprehensively reviewed human evidence that sex moderates susceptibility to environmental toxicants and concluded that, in most instances, males are more vulnerable. However, their conclusions were based mostly on exposure to lead, methylmercury and organophosphates, with little mention of PCBs that were the focus of the current study.…”

Climatic conditions and child height: Sex-specific vulnerability and the protective effects of sanitation and food markets in Nepal

“…We find the underlying patterns to be sex-specific, with systematic differences in how later heights relate to NDVI fluctuations that occurred during infancy and pregnancy. These differences are consistent with both gender bias in infant care (Maccini and Yang, 2009) and physiological differences in fetal development before the sex of the child is known (DiPietro and Voegtline, 2015, Rosenfeld, 2015). We find that improved household sanitation and more commercialized food markets limit both kinds of vulnerability, providing significant protection from agroclimatic conditions for both pregnant mothers and infants.…”

“…There is a growing body of evidence suggesting differential effects of prenatal stress on male and female fetuses on perinatal outcomes (Aibar et al, 2012, Mulla et al, 2013, Persson and Fadl, 2014) and adult health (Scholte et al, 2015). In general, female fetuses are more resilient and adaptive to stress than are male fetuses (DiPietro and Voegtline, 2015, Rosenfeld, 2015). Evidence from studies that examined the effects of stressors such as intrauterine lead and pesticide exposure, and maternal alcohol and drug use, suggest that exposed male fetuses are more likely to be born preterm and have poorer scores on developmental assessments than females (Rosenfeld, 2015).…”

A longitudinal model of executive function development from birth through adolescence in children born very or extremely preterm

“…The overall significant sex difference in outcome in late adolescence could be attributed to the summed direct and indirect sex effects. The risks associated with male sex have been investigated by others, although the specific mechanisms are yet to be fully explored (DiPietro & Voegtline, 2017;Smith, Alexander, Rosenkrantz, Sadek, & Fitch, 2014). Previous studies suggest that female brains have a greater potential for reorganization of function, which might contribute to a better recovery from the impact of early disturbances in females as compared to males (Anderson, Anderson, Northam, Jacobs, & Catroppa, 2001).…”