Fetal Programming of Semen Quality: Establishment of a cohort and case studies of tobacco smoking and per- and polyfluoroalkyl substances

The purpose of this thesis was to investigate if selected exposures in fetal life have long-term consequences for male reproductive function. To examine this, we established the world’s largest male offspring cohort specifically designed to study the fetal programming of semen quality hypothesis. The Fetal programming of Semen Quality (FEPOS) cohort consists of 1,058 sons (participation rate 19%) and their mothers, nested within the Danish National Birth Cohort (DNBC). The sons answered a questionnaire, underwent a clinical examination, and delivered a semen and blood sample. Information on fetal exposures were available from a DNBC interview of the mothers and from a blood sample drawn during pregnancy, both
primarily in first trimester.
Based on our results, there is evidence that fetal exposure to both maternal and paternal smoking and PFAS are associated with several key aspects of male reproductive function. Additional studies focusing on paternal exposures are needed and further interest into the fetal masculinization programming window is warranted to identify the mechanisms linking parental smoking to impaired semen quality. More studies on fetal PFAS exposure and reproductive function taking mixture effects and both legacy and emerging PFAS into account are needed.