子宫内接触己烯雌酚(DES)的男性所生育子女的出生缺陷。
Birth defects in children of men exposed in utero to diethylstilbestrol (DES).
作者信息
Tournaire Michel, Devouche Emmanuel, Epelboin Sylvie, Cabau Anne, Dunbavand Annabel, Levadou Anne
机构信息
Assistance publique-Hôpitaux de Paris, 75014 Paris, France; Université Paris Descartes, 75006 Paris, France.
Université Paris Descartes, 75006 Paris, France; Laboratoire psychopathologie et processus de santé EA4057, 92100 Boulogne-Billancourt, France.
出版信息
Therapie. 2018 Oct;73(5):399-407. doi: 10.1016/j.therap.2018.02.007. Epub 2018 Mar 3.
OBJECTIVE
Prenatal exposure to diethylstilbestrol (DES) is associated with adverse effects, including genital anomalies and cancers in men and women. Animal studies showed birth defects and tumors in the offspring of mice prenatally exposed to DES. In humans, birth defects, such as hypospadias were observed in children of prenatally exposed women. The aim of this research was to assess the birth defects in children of prenatally exposed men.
METHODS
In a retrospective study conceived by a patients' association (Réseau DES France), the reports of men prenatally exposed to DES on adverse health effects in their children were compared with those of unexposed controls and general population.
RESULTS
An increased incidence of two genital anomalies, cryptorchidism (OR=5.72; 95% CI 1.51-21.71), and hypoplasia of the penis (OR=22.92; 95% CI 3.81-137.90), was observed in the 209 sons of prenatally exposed men compared with controls, but hypospadias incidence was not increased in comparison with either the controls or the general population. No increase of genital anomalies was observed in daughters.
CONCLUSION
With caution due to the methods and to the small numbers of defects observed, this work suggests an increased incidence of two male genital tract defects in sons of men prenatally exposed to DES. This transgenerational effect, already observed in animals and in the offspring of women prenatally exposed to DES, could be the result of epigenetic changes transmitted to the subsequent generation through men.
目的
产前接触己烯雌酚(DES)会产生不良影响,包括男性和女性的生殖器异常及癌症。动物研究表明,产前接触DES的小鼠后代会出现出生缺陷和肿瘤。在人类中,产前接触DES的女性所生子女中观察到了诸如尿道下裂等出生缺陷。本研究的目的是评估产前接触DES的男性所生子女的出生缺陷情况。
方法
在一项由患者协会(法国DES网络)构思的回顾性研究中,将产前接触DES的男性关于其子女健康不良影响的报告与未接触DES的对照组及一般人群的报告进行了比较。
结果
与对照组相比,产前接触DES的男性的209名儿子中,两种生殖器异常的发生率有所增加,即隐睾症(比值比[OR]=5.72;95%置信区间[CI]为1.51 - 21.71)和阴茎发育不全(OR=22.92;95%CI为3.81 - 137.90),但与对照组或一般人群相比,尿道下裂的发生率并未增加。在女儿中未观察到生殖器异常发生率增加。
结论
由于研究方法及观察到的缺陷数量较少,需谨慎看待,本研究表明产前接触DES的男性的儿子中两种男性生殖道缺陷的发生率有所增加。这种在动物及产前接触DES的女性后代中已观察到的跨代效应,可能是通过男性传递给后代的表观遗传变化的结果。