Abstract

Abstract Study question Is exposure to maternal perceived stress during pregnancy associated with reproductive function in adult male offspring? Summary answer While maternal perceived stress was prevalent in the first trimesters of pregnancy, our preliminary findings indicate little association with reproductive function in young men. What is known already Though studies in animals point to a connection between prenatal exposure to maternal stress and reproductive function in offspring, the underlying biological mechanisms generating a deficit remain largely unclear. In humans, the few available studies focus on exposure to bereavement or other relatively strong objective stressful life events. Our individual perception of stress is, however, more likely the sum of a complex process involving both the actual input, previous experiences, coping strategies and support from our surroundings. Study design, size, duration Young men and their mothers were identified through records from the Danish National Birth Cohort (DNBC). Information on exposure, i.e. maternal perceived life and emotional stress, was available from telephone interviews conducted at approximately 30 weeks of gestation (1996 to 2001). Recruitment of the young men lasted from 2017 to 2019 with 1058 participants enrolled in the final FEPOS cohort. Participants/materials, setting, methods Each of the 1058 men in the FEPOS cohort completed an online questionnaire and clinical examinations and provided a blood and semen sample. Information on potential pre- and postnatal confounders was retrieved from the DNBC, the Danish National Patient Register and the Danish Medical Birth Register. We applied negative binomial regression models to examine associations between maternal perceived life and emotional stress scores and semen quality, testicular size and reproductive hormones among the young men. Main results and the role of chance Among the 1052 young men included in preliminary analyses, the majority was exposed to maternal perceived life and/or emotional stress (76% and 83%, respectively) during the first trimesters. Life stress was predominantly related to the actual pregnancy (48%), maternal disease (19%) or occupational conditions (33%). Emotional stress included especially being touchy (58%), sad (38%) or tense (36%), covering aspects of both stress, depression and anxiety. Overall, results indicate little association between maternal stress scores and measures of semen quality and testicular size. Our study involves a large cohort with prospectively collected exposure data and direct measures of several male reproductive outcomes. We applied inverse probability weighting to account for selection into the FEPOS cohort and included a range of a priori selected maternal confounders in our models. Limitations, reasons for caution The male fetus may be particularly sensitive to exposure during the differentiation of reproductive tissues (8–14 weeks of gestation). Our self-reported measures of exposure cover the first 30 weeks of gestation. Absence of association may, thus, be due to a lack of specific information on timing of symptoms. Wider implications of the findings: While our preliminary findings may appear reassuring, further efforts to improve our understanding of maternal stress in relation to fetal health and potential consequences later in life are needed. Trial registration number Not applicable

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