The association between in utero exposure to maternal psychological stress and female reproductive function in adolescence: A prospective cohort study

BACKGROUND: Experimental studies suggest that prenatal stress affects reproductive function in female offspring, but human evidence is sparse and inconsistent. In this present study, we aim to investigate whether maternal psychological stress, quantified as stressful life events during pregnancy, affect reproductive function in the female offspring. METHOD: In a large population-based pregnancy cohort study (The Raine Study) continuously followed from prenatal life through to adolescence we examined the association between the number of maternal stressful life events in both early and late gestation and subsequent ovarian and uterine function in 228 female adolescent offspring. Mothers prospectively reported stressful life events during pregnancy at 18 and 34 weeks using a standardized 10-point questionnaire. Female offspring (n ​= ​228) age 14–16 years underwent gynecological examination including transabdominal abdominal ultrasound (TAUS) to measure uterine volume and ovarian AFC. Plasma samples on day 2–6 of the spontaneous menstrual cycle measured circulating AMH and inhibin B. Multivariate linear regression analysis was used to examine the associations between maternal stressful life events and reproductive function in female offspring. Adolescents taking hormonal contraception were excluded. RESULTS: Most adolescents (145/228, 64%) were exposed to at least one stressful life event in early gestation and around half (125/228, 55%) were exposed to at least one in later gestation. Exposure to one or more maternal stressful life events in late gestation was associated with a greater uterine volume (β ​= ​0.13, 95% CI 0.04; 0.23) and higher ovarian AFC (β ​= ​0.19, 95% CI 0.02; 0.35) at age 14–16 years. No associations between maternal stressful events in late gestation and reproductive function were identified. No associations between stressful life events in early or late gestation and circulating AMH or Inhibin B were observed. CONCLUSION: Maternal psychological stress in late, but not early gestation was associated with a significantly greater uterine volume and ovarian antral follicle count (AFC) in adolescent offspring but did not affect ovarian production of antimullerian hormone (AMH) or Inhibin B. These findings suggest that female reproductive function is influenced by prenatal exposure to stress.