Maternal smoking during pregnancy specifically reduces human fetal desert hedgehog gene expression during testis development
Maternal smoking during pregnancy specifically reduces human fetal desert hedgehog gene expression during testis development
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DOI：
10.1210/jc.2007-1860
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发表时间：
2008-02-01
影响因子：
5.8
通讯作者：
O'Shaughnessy, Peter J.
中科院分区：
文献类型：
--
作者：
Fowler, Paul A.;Cassie, Sarah;O'Shaughnessy, Peter J.
背景：孕妇在孕期吸烟会增加隐睾症和尿道下裂，并降低男孩的睾丸大小和生育力，其机制尚不清楚。目的：本研究的目的是确定母亲吸烟是否与男性胎儿内分泌学、睾丸基因表达和肝脏香烟烟雾化学物质浓度的变化有关。设计：这是一项对男性胎儿的观察性研究，比较母亲在怀孕期间吸烟和不吸烟的情况。背景：这项研究是在阿伯丁、格拉斯哥和诺丁汉和麦考利学院(Aberdeen)进行的。患者/参与者：睾丸、血液、血液、肝脏主要观察指标：睾酮、绒毛膜促性腺激素、促黄体生成素、可替宁；30个生殖/发育基因的表达；肝脏中16种多环芳烃的浓度；以及Sertoli的Leydig。结果：两组在胎儿大小、睾丸重量、细胞数、曲细精管直径、外周血中黄体生成素和睾酮水平等方面均无显著差异。吸烟母亲的胎儿吸烟范围、可替宁水平和肝脏多环芳烃浓度是母亲吸烟的重要预测因素(P<；0.001)。只有支持细胞特异性基因沙漠刺猬(Dhh)被母亲吸烟显著改变(减少1.8%，P=0.013)。结论：在男性和小鼠中，dhh信号减弱的后果与妊娠母亲吸烟对儿子影响的流行病学一致。鉴于没有观察到母亲吸烟的其他影响，我们得出结论，降低DHH是将母亲怀孕吸烟与男性后代生殖发育障碍联系起来的机制的一部分。
Context: Maternal cigarette smoking during gestation increases cryptorchidism and hypospadias and reduces testis size and fertility in sons by unknown mechanisms.Objective: The objective of the study was to determine whether maternal smoking is linked with changes in male human fetal endocrinology, testis gene expression, and liver concentrations of cigarette smoke chemicals.Design: This was an observational study of the male fetus, comparing pregnancies during which the mothers either did or did not smoke.Setting: The study was conducted at the universities of Aberdeen, Glasgow, and Nottingham and Macaulay Institute (Aberdeen).Patients/Participants: Testes, blood, and livers were collected from 69 morphologically normal human male fetuses of women undergoing elective termination of normal second-trim ester pregnancies.Main Outcome Measures: Testosterone, human chorionic gonadotropin, LH, and cotinine; expression of 30 reproductive/developmental genes; liver concentrations of 16 polycyclic aromatic hydrocarbons; and Leydig, Sertoli. and germ cell numbers were determined.Results: There were no significant differences in fetal size, testis weight, cell numbers, seminiferous tubule diameter, or circulating LH and testosterone. Fetuses from smoking mothers had smoking range cotinine levels and liver concentrations of polycyclic aromatic hydrocarbons that were significant predictors of maternal smoking (P < 0.001). Only the Sertoli cell-specific gene, desert hedgehog (DHH), was significantly altered by maternal smoking (reduced 1.8-fold, P = 0.013).Conclusions: The consequences of reduced DHH signaling in men and mice are consistent with epidemiology for effects of gestational maternal smoking on sons. Given the absence of other observed effects of maternal smoking, we concluded that reduced DHH is part of a mechanism linking maternal gestational smoking with impaired reproductive development in male offspring.