Prenatal glucocorticoids and maternal smoking during pregnancy independently program adult nicotine dependence in daughters: a 40-year prospective study.
Prenatal glucocorticoids and maternal smoking during pregnancy independently program adult nicotine dependence in daughters: a 40-year prospective study.
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DOI：
10.1016/j.biopsych.2013.07.024
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发表时间：
2014-01-01
影响因子：
10.6
通讯作者：
Buka, Stephen L.
中科院分区：
文献类型：
--
作者：
Stroud, Laura R.;Papandonatos, George D.;Shenassa, Edmond;Rodriguez, Daniel;Niaura, Raymond;LeWinn, Kaja Z.;Lipsitt, Lewis P.;Buka, Stephen L.
关键词：
母亲孕期吸烟(MSDP)是子代尼古丁依赖(ND)的独立危险因素，但机制尚不清楚。我们研究了40年来胎儿期糖皮质激素(皮质醇)和雄激素(睾酮)与子代ND的关系，以及产前糖皮质激素和雄激素可能介导MSDP和子代ND之间联系的可能性。参与者是来自新英格兰家庭研究的1086对母亲-成年后代(59%是女性)，这是一项对合作围产期项目40年的纵向跟踪调查。MSDP在每次产前检查时进行前瞻性评估。从妊娠晚期孕妇血清中检测孕妇皮质醇、睾酮和可替宁(尼古丁代谢物)。通过结构化访谈评估子代终生ND。显著的双变量关联出现：a)MSDP/可替宁和终生ND，以及b)母亲皮质醇和终生ND，仅对女儿。在多变量模型中，母亲皮质醇和MSDP/可替宁仍然与女儿终生ND的几率增加显著且独立相关。但皮质醇不能调节MSDP-LIFE ND之间的关系。母体睾丸素和后代ND之间没有关联。研究结果首次证实40岁以上成人ND仅在女婴中进行产前糖皮质激素治疗。我们的研究强调了导致女儿患新城疫风险增加的两条独立的产前途径：产前糖皮质激素升高和MSDP/尼古丁暴露。40年来，糖皮质激素和MSDP编程对女儿的特定影响突出了人类性别二态编程效应的广泛性和持久性。结果不支持后代ND的雄激素计划。
Maternal smoking during pregnancy (MSDP) is an independent risk factor for offspring nicotine dependence (ND), but mechanisms remain unknown. We investigated prenatal glucocorticoid (cortisol) and androgen (testosterone) associations with offspring ND over 40 years, and the possibility that prenatal glucocorticoids and androgens would mediate links between MSDP and offspring ND. Participants were 1,086 mother-adult offspring pairs (59% female) from the New England Family Study, a 40-year longitudinal follow up of the Collaborative Perinatal Project. MSDP was assessed prospectively at each prenatal visit. Maternal cortisol, testosterone, and cotinine (nicotine metabolite), were assayed from third trimester maternal sera. Offspring lifetime ND was assessed via structured interview. Significant bivariate associations emerged for: a) MSDP/cotinine and lifetime ND, and b) maternal cortisol and lifetime ND, for daughters only. In multivariate models, maternal cortisol and MSDP/cotinine remained significantly and independently associated with increased odds of daughters’ lifetime ND. However, cortisol did not mediate the MSDP-lifetime ND relation. No associations emerged between maternal testosterone and offspring ND. Results provide the first evidence in support of prenatal glucocorticoid programming of adult ND over 40 years in daughters only. Our study highlights two independent prenatal pathways leading to increased risk for ND in daughters: elevated prenatal glucocorticoids and MSDP/nicotine exposure. Daughter-specific effects of glucocorticoid and MSDP programming over 40 years highlight the breadth and persistence of sexually dimorphic programming effects in humans. Results do not support androgen programming of offspring ND.
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