Unité d'Endocrinologie-Gynécologie Pédiatrique, Service de Pédiatrie 1, Hôpital Arnaud-de-Villeneuve, CHU Montpellier et Université Montpellier 1, 34295 Montpellier, Cedex 5, France.
Hum Reprod. 2011 Nov;26(11):3155-62. doi: 10.1093/humrep/der283. Epub 2011 Aug 25.
Over the past decades, an increasing trend in male external genital malformations such as cryptorchidism and hypospadias has led to the suspicion that environmental chemicals are detrimental to male fetal sexual development. Several environmental pollutants, including organochlorine pesticides, polychlorinated biphenyls, bisphenol A, phthalates, dioxins and furans have estrogenic and anti-androgenic activity and are thus considered as endocrine-disrupting chemicals (EDCs). Since male sex differentiation is critically dependent on the normal production and action of androgens during fetal life, EDCs may be able to alter normal male sex differentiation.
The objective of this study was to determine the incidence of external genital malformations in a population of full-term newborn males in southern France. We also performed a case-control study to identify the risk factors for male external genital malformations, with a focus on parental occupational exposure to EDCs.
Over a 16-month period, 1615 full-term newborn males with a birth weight above 2500 g were registered on a level-1 maternity ward, and the same pediatrician systematically examined 1442 of them (89%) for cryptorchidism, hypospadias and micropenis. For every male newborn with genital malformation, we enrolled nearly two males matched for age, parity and term. All parents of the case and control newborns were interviewed about pregnancy aspects, personal characteristics, lifestyle and their occupational exposure to EDCs using a detailed questionnaire. RESULTS We report 39 cases of genital malformation (2.70%), with 18 cases of cryptorchidism (1.25%), 14 of hypospadias (0.97%), 5 of micropenis (0.35%) and 2 of 46,XY disorders of sexual differentiation (DSD; 0.14%). We observed a significant relationship between newborn cryptorchidism, hypospadias or micropenis and parental occupational exposure to pesticides [odds ratio (OR) = 4.41; 95% confidence interval (95% CI), 1.21-16.00]. Familial clustering for male external genital malformations (OR = 7.25; 95% CI, 0.70-74.30) and medications taken by mothers during pregnancy (OR = 5.87; 95% CI, 0.93-37.00) were associated with the risk of cryptorchidism, hypospadias and micropenis, although the association was not statistically significant.
Although the causes of male genital malformation are multifactorial, our data support the hypothesis that prenatal contamination by pesticides may be a potential risk factor for newborn male external genital malformation and it should thus be routinely investigated in all undervirilized newborn males.
在过去几十年中，男性外生殖器畸形（如隐睾和尿道下裂）的发病率呈上升趋势，这使得人们怀疑环境化学物质对男性胎儿的性发育有害。一些环境污染物，包括有机氯农药、多氯联苯、双酚 A、邻苯二甲酸酯、二恶英和呋喃，具有雌激素和抗雄激素活性，因此被认为是内分泌干扰化学物质（EDCs）。由于男性性别分化在很大程度上依赖于胎儿期雄激素的正常产生和作用，因此 EDCs 可能能够改变正常的男性性别分化。
本研究旨在确定法国南部足月新生儿男性外生殖器畸形的发生率。我们还进行了病例对照研究，以确定男性外生殖器畸形的危险因素，重点关注父母接触 EDCs 的职业暴露。
在 16 个月的时间里，在一级产科病房登记了 1615 名出生体重超过 2500 克的足月新生儿，同一名儿科医生对其中 1442 名（89%）进行了隐睾、尿道下裂和小阴茎的系统检查。对于每一个有生殖器畸形的男性新生儿，我们招募了近两个年龄、产次和足月匹配的男性新生儿作为对照。所有病例和对照新生儿的父母都接受了关于妊娠情况、个人特征、生活方式以及他们接触 EDCs 的职业暴露的详细问卷调查。
我们报告了 39 例生殖器畸形（2.70%），其中 18 例隐睾（1.25%）、14 例尿道下裂（0.97%）、5 例小阴茎（0.35%）和 2 例 46,XY 性发育障碍（DSD；0.14%）。我们观察到新生儿隐睾、尿道下裂或小阴茎与父母接触农药的职业暴露之间存在显著关系[比值比（OR）=4.41；95%置信区间（95%CI），1.21-16.00]。男性外生殖器畸形的家族聚集（OR=7.25；95%CI，0.70-74.30）和母亲在妊娠期间服用的药物（OR=5.87；95%CI，0.93-37.00）与隐睾、尿道下裂和小阴茎的风险相关，尽管这种关联没有统计学意义。
尽管男性生殖器畸形的原因是多因素的，但我们的数据支持这样一种假设，即产前接触农药可能是新生儿男性外生殖器畸形的潜在危险因素，因此应在所有未发育的新生儿男性中常规进行调查。
