Fetal exposure to maternal cigarette smoking and male reproductive function in young adulthood

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Katia Keglberg Hærvig
Kajsa Ugelvig Petersen
Aleksander Giwercman
Hougaard, Karin Sørig
Birgit Bjerre Høyer
Christian Lindh
Cecilia Høst Ramlau-Hansen
Nybo Andersen, Anne-Marie
Gunnar Toft
Bonde, Jens Peter
Tøttenborg, Sandra Søgaard

Maternal smoking during pregnancy constitutes a potential, major risk factor for adult male reproductive function. In the hitherto largest longitudinal cohort, we examined biomarkers of reproductive function according to maternal smoking during the first trimester and investigated whether associations were mitigated by smoking cessation prior to the fetal masculinization programming window. Associations between exposure to maternal smoking and semen characteristics, testicular volume and reproductive hormones were assessed among 984 young men from the Fetal Programming of Semen Quality (FEPOS) cohort. Maternal smoking was assessed through interview data and measured plasma cotinine levels during pregnancy. We applied negative binomial, logistic and linear regression models to estimate differences in outcomes according to levels of maternal smoking. Sons of light smokers (≤ 10 cigarettes/day) had a 19% (95% CI − 29%, − 6%) lower sperm concentration and a 24% (95% CI − 35%, − 11%) lower total sperm count than sons of non-smokers. These estimates were 38% (95% CI − 52%, − 22%) and 33% (95% CI − 51%, − 8%), respectively, for sons of heavy smokers (> 10 cigarettes/day). The latter group also had a 25% (95% CI 1%, 54%) higher follitropin level. Similarly, sons exposed to maternal cotinine levels of > 10 ng/mL had lower sperm concentration and total sperm count. Smoking cessation prior to gestational week seven was not associated with a higher reproductive capacity. We observed substantial and consistent exposure–response associations, providing strong support for the hypothesis that maternal smoking impairs male reproductive function. This association persisted regardless of smoking cessation in early pregnancy.

Originalsprog	Engelsk
Tidsskrift	European Journal of Epidemiology
Vol/bind	37
Sider (fra-til)	525–538
Antal sider	13
ISSN	0393-2990
DOI	https://doi.org/10.1007/s10654-022-00869-2
Status	Udgivet - 2022

Bibliografisk note

Funding Information:
We are grateful to all participants and to biomedical laboratory technicians 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, and Cecilia Tingsmark for conducting the morphology analysis. Moreover, we wish to thank Anna Rönnholm, Marie Bengtsson, Åsa Amilon, at the Division of Occupational and Environmental Medicine at Lund University, Sweden, for performing the analyses of chemicals and to the Department of Clinical Biochemistry at Aarhus University Hospital, Denmark, for doing the hormone 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. Follow-up of mothers and children have been supported by the Danish Medical Research Council (SSVF 0646, 271-08-0839/06-066023, O602-01042B, 0602-02738B), the Lundbeck Foundation (195/04, R100-A9193), The Innovation Fund Denmark 0603-00294B (09-067124), the Nordea Foundation (02-2013-2014), Aarhus Ideas (AU R9-A959-13-S804), University of Copenhagen Strategic Grant (IFSV 2012), and the Danish Council for Independent Research (DFF—4183-00594 and DFF—4183-00152).

Funding Information:
The FEPOS cohort and this study is part of the ReproUnion collaboration and co-financed by the European Union, Interreg V ÖKS, the Lundbeck Foundation, the Capital Region of Denmark, Medical Doctor Sofus Carl Emil Friis and Spouse Olga Doris Friis's Grant, Axel Muusfeldt’s Foundation, A.P. Møller Foundation, Dagmar Marshalls Foundation and the Helse Foundation.

Funding Information:
Aleksander Giwercman has received research grants from Ferring Pharmaceuticals and personal fees from Besins Healthcare Nordic and Sandoz, unrelated to the submitted work. The authors declare that they have no other conflicts of interest.

Publisher Copyright:
© 2022, Springer Nature B.V.

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