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.

怀孕期间母亲吸烟是成年男性生殖功能的潜在主要危险因素。在迄今为止最大的纵向队列中，我们根据孕早期母亲吸烟检查了生殖功能的生物标志物，并调查了在胎儿男性化编程窗口之前戒烟是否减轻了相关性。在来自胎儿精液质量规划 (FEPOS) 队列的 984 名年轻男性中评估了母亲吸烟与精液特征、睾丸体积和生殖激素之间的关联。通过访谈数据评估母亲吸烟情况，并在怀孕期间测量血浆可替宁水平。我们应用了负二项式，逻辑和线性回归模型，以根据母亲吸烟水平估计结果的差异。轻度吸烟者的儿子（≤ 10 支/天）的精子浓度降低 19% (95% CI - 29%, - 6%)，总精子数量降低 24% (95% CI - 35%, - 11%)比不吸烟者的儿子。对于重度吸烟者（> 10 支/天）的儿子，这些估计值分别为 38%（95% CI - 52%， - 22%）和 33%（95% CI - 51%， - 8%）。后一组的促卵泡激素水平也高出 25% (95% CI 1%, 54%)。同样，暴露于母亲可替宁水平 > 10 ng/mL 的儿子精子浓度和总精子数较低。在妊娠第 7 周之前戒烟与更高的生殖能力无关。我们观察到大量且一致的暴露-反应关联，为母亲吸烟会损害男性生殖功能的假设提供强有力的支持。无论怀孕早期是否戒烟，这种关联都会持续存在。