https://orcid.org/0000-0003-3296-0121
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Abstract
Background
Prenatal exposures may contribute to male infertility in adult life, but large-scale epidemiological evidence is still lacking. The Fetal Programming of Semen quality (FEPOS) cohort was founded to provide means to examine if fetal exposures can interfere with fetal reproductive development and ultimately lead to reduced semen quality and reproductive hormone imbalances in young adult men.
Methods
Young adult men at least 18 years and 9 months of age born to women in the Danish National Birth Cohort living in relative proximity to Copenhagen or Aarhus and for whom a maternal blood sample and two maternal interviews during pregnancy were available were invited to FEPOS. Recruitment began in March 2017 and ended in December 2019. The participants answered a comprehensive questionnaire and underwent a physical examination where they delivered a semen, urine, and hair sample, measured their own testicular volume, and had blood drawn.
Results
In total 21,623 sons fulfilled eligibility criteria of whom 5697 were invited and 1058 participated making the response rate 19%. Semen characteristics did not differ between sons from the Copenhagen and Aarhus clinics. When comparing the FEPOS semen parameters to similar cohorts, the median across all semen characteristics was slightly lower for FEPOS participants, although with smaller variation.
Conclusion
With its 1058 young adult men, the FEPOS cohort is the largest population-based male-offspring cohort worldwide specifically designed to investigate prenatal determinants of semen quality. Wide-ranging information on maternal health, lifestyle, socioeconomic status, occupation, and serum concentrations of potential reproductive toxicants during pregnancy combined with biological markers of fertility in their sons collected after puberty allow for in-depth investigations of the ‘fetal origins of adult disease hypothesis’.
Acknowledgments
We are grateful to all participants and to biomedical laboratory technologists Marianne Lipka Flensborg and Joan Dideriksen for running the clinics and collecting data. We also thank Josefine Rahbæk Larsen for assisting with recruitment and data entry, Cecilia Tingsmark for doing the morphology analysis, and Aleksandra Kondic for DNA fragmentation analyses.
The Danish National Birth Cohort was established with a significant grant from the Danish National Research Foundation. Additional support was obtained from the Danish Regional Committees, the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, the Health Foundation and other minor grants. The DNBC Biobank has been supported by the Novo Nordisk Foundation and the Lundbeck Foundation.
Data Sharing Statement
The FEPOS cohort is managed by researchers from multiple Danish institutions and is overseen by a scientific reference group consisting of researchers from the DNBC management group amongst others. The cohort is considered an open access resource for researchers with projects that fall within the policy and overall aim of the DNBC [https://www.dnbc.dk/access-to-dnbc-data]. The scientific management team reserves the right to prioritize ongoing projects and encourages external applicants to collaborate with Danish researchers including principal investigator of FEPOS, Sandra Søgaard Tøttenborg [[email protected]]. Further questions can be directed to the DNBC administrative office [[email protected]].
Author Contributions
Birgit Bjerre Høyer, Ina Olmer Specht, Jens Peter Bonde, Anne-Marie Nybo Andersen, Jørn Olsen, Christian Lindh and Aleksander Giwercman acquired funding. All authors made substantial contributions to conception and design. Data were acquired by Katia Keglberg Hærvig, Birgit Bjerre Høyer, Aleksander Giwercman, Cecilia Høst Ramlau-Hansen, Gunnar Toft, Jens Peter Bonde, Christian Lindh, and Sandra Søgaard Tøttenborg. The original draft was prepared by Katia Keglberg Hærvig. All authors contributed to data analysis and interpretation, revision of the article, gave final approval of the version to be published, and agreed to be accountable for all aspects of the work.
Disclosure
Prof. Dr. Aleksander Giwercman reports grants from Ferring Pharmaceuticals and personal fees from Besins Healthcare Nordic and Sandoz, outside the submitted work. The authors declare that they have no other possible conflicts of interest in this work.