Prenatal exposure to stressful life events is associated with masculinized anogenital distance (AGD) in female infants

• Anogenital distance (AGD) is a marker of prenatal androgen exposure.
• Here, we examine prenatal exposure to life events stress and AGD in humans.
• Prenatal exposure to stressful life events was associated with longer AGD in females.
• Prenatal stress was weakly associated with shorter AGD in male infants.
• Further research is needed to understand underlying mechanisms.

In animal models, prenatal stress programs reproductive development in the resulting offspring, however little is known about effects in humans. Anogenital distance (AGD) is a commonly used, sexually dimorphic biomarker of prenatal androgen exposure in many species. In rodents, prenatally stressed males have shorter AGD than controls (suggesting lower prenatal androgen exposure), whereas prenatally stressed females have longer AGD than controls (suggesting greater prenatal androgen exposure). Our objective was to investigate the relationship between stressful life events in pregnancy and infant AGD. In a prospective cohort study, pregnant women and their partners reported exposure to stressful life events during pregnancy. Pregnancies in which the couple reported 4 + life events were considered highly stressed. After birth (average 16.5 months), trained examiners measured AGD in the infants (137 males, 136 females). After adjusting for age, body size and other covariates, females born to couples reporting high stress had significantly longer (i.e. more masculine) AGD than females born to couples reporting low stress (p = 0.015). Among males, high stress was weakly, but not significantly, associated with shorter AGD. Our results suggest prenatal stress may masculinize some aspects of female reproductive development in humans. More sensitive measures of prenatal stress and additional measures of reproductive development are needed to better understand these relationships and clarify mechanisms.