Fetal exposure to maternal stress and male reproductive function in a cohort of young adults

OBJECTIVE: To study associations between maternal stress during pregnancy and reproductive function in young men.

DESIGN: A cohort study nested in a population-based birth cohort.

SETTING: Not applicable.

PATIENTS: Young men (n = 1,052; response rate, 19%) participated in the Fetal Programming of Semen Quality cohort from 2017 to 2019. They were recruited from pregnancies in the Danish National Birth Cohort (1996-2001). The men completed an online questionnaire, clinical examination, and collection of blood and semen samples.

EXPOSURES: Information on maternal life and emotional stresses was available from a telephone interview covering the interval from the beginning of pregnancy to approximately gestational week 30.

MAIN OUTCOME MEASURE(S): We applied negative binomial, linear, and logistic regression to examine associations between life and emotional stress scores (range, 0-18) and reproductive function. The primary outcomes were measures of semen quality, and the secondary outcomes included reproductive hormone levels and testicular volume.

RESULT(S): Overall, we observed no negative associations between maternal life or emotional stress and male reproductive function. Maternal emotional stress was associated with higher total sperm count (16% difference; 95% confidence interval [CI], 1-33), serum estradiol (11% difference; 95% CI, 2-21), and calculated free testosterone (β = 17.8; 95% CI, 1.26-34.3). The results were robust to inverse probability weighting introduced to account for selection.

CONCLUSION(S): Although our findings may appear reassuring, further efforts to validate the measures of stress during pregnancy and improve our understanding of the full spectrum of fetal stress exposures and consequences for health later in life are needed.