Division of Applied Medicine, Institute of Medical Sciences, University of Aberdeen, Centre for Reproductive Endocrinology and Medicine, Foresterhill, Aberdeen AB25 2ZD, United Kingdom.
J Clin Endocrinol Metab. 2011 Sep;96(9):E1502-6. doi: 10.1210/jc.2011-1100. Epub 2011 Jul 13.
Fertility, sperm counts, and testis weights are reduced in men whose mothers smoked in pregnancy. Animal studies suggest this could be due to impaired androgen action. Anogenital distance (AGD) provides a readout of fetal androgen exposure and is reduced by in utero exposure to harmful chemicals in rodents. This study assessed whether maternal cigarette smoking disturbs AGD in the second trimester human fetus.
Morphological indices, including AGD, and circulating cotinine concentrations were measured in 83 electively terminated, normally progressing, second-trimester fetuses between 11 and 20 wk gestation.
A gender difference in AGD (1.4-fold longer in males) was already apparent at 11-13 wk, rising to 2.00-fold longer in males at 17-20 wk gestation. In males, AGD and AGD normalized against ponderal index (a measure of fetal leanness) were significantly increased by maternal smoking (1.19- and 1.31-fold, respectively). The difference between smoke-exposed and nonexposed male AGD was greatest at 11-13 wk (1.25-fold) but had declined to 1.01-fold by 17-20 wk gestation. AGD in females was not affected by maternal cigarette smoking.
Androgen programming of masculinization occurs before 11-13 wk gestation in the human because AGD is already significantly longer in male fetuses by that stage. AGD reaches the 2-fold difference reported for the neonate by 17-20 wk gestation. Significantly longer AGD in smoke-exposed males was surprising and may indicate increased androgen exposure in the early programming window. Convergence of AGD by late second trimester suggests, however, that by birth, male AGD may be shorter in smoke-exposed individuals.
在母亲怀孕期间吸烟的男性中，生育能力、精子数量和睾丸重量下降。动物研究表明，这可能是由于雄激素作用受损所致。肛生殖器距离（AGD）提供了胎儿雄激素暴露的指标，并且在啮齿动物中，由于暴露于宫内有害化学物质而减少。本研究评估了母亲吸烟是否会在第二个妊娠中期干扰人类胎儿的 AGD。
在 83 名选择性终止的正常进展的第二个妊娠中期胎儿中，测量了形态学指标，包括 AGD 和循环可替宁浓度，这些胎儿在 11 至 20 周妊娠时。
在 11-13 周时，AGD 已经存在性别差异（男性长 1.4 倍），在 17-20 周妊娠时，男性长 2.0 倍。在男性中，AGD 和 AGD 与体脂指数（衡量胎儿瘦度的指标）的比值均因母亲吸烟而显著增加（分别增加 1.19 倍和 1.31 倍）。暴露于吸烟和未暴露于吸烟的男性 AGD 之间的差异在 11-13 周时最大（1.25 倍），但在 17-20 周妊娠时降至 1.01 倍。女性 AGD 不受母亲吸烟的影响。
在人类中，雄激素对男性化的编程发生在 11-13 周之前，因为在这个阶段，男性胎儿的 AGD 已经明显更长。AGD 在 17-20 周妊娠时达到了报告的新生儿的 2 倍差异。暴露于吸烟的男性中 AGD 显著延长令人惊讶，这可能表明在早期编程窗口中雄激素暴露增加。然而，AGD 在第二个妊娠中期晚期的收敛表明，在出生时，暴露于吸烟的个体的男性 AGD 可能较短。
