Guzmán Carolina, Zambrano Elena
Departamento de Biologia de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirin, Tlalpan, México.
Rev Invest Clin. 2007 Jan-Feb;59(1):73-81.
Different perturbations during fetal and postnatal development unleash endocrine adaptations that permanently alter metabolism, increasing the susceptibility to develop later disease, process known as "developmental programming." Endocrine disruptor compounds (EDC) are widely spread in the environment and display estrogenic, anti-estrogenic or anti-androgenic activity; they are lipophilic and stored for long periods in the adipose tissue. Maternal exposure to EDC during pregnancy and lactation produces the exposure of the fetus and neonate through placenta and breast milk. Epidemiological and experimental studies have demonstrated reproductive alterations as a consequence of intrauterine and/or neonatal exposure to EDC. Diethystilbestrol (DES) is the best documented compound, this synthetic estrogen was administered to pregnant women in the 1950s and 1960s to prevent miscarriage. It was implicated in urogenital abnormalities in children exposed in utero and was withdrawn from the market. The "DES daughters" are women with high incidence of vaginal hypoplasia, spontaneous abortion, premature delivery, uterine malformation, menstrual abnormalities and low fertility. The "DES sons" show testicular dysgenesis syndrome, which is characterized by hypospadias, cryptorchidism and low semen quality. This entity is also associated wtih fetal exposure to anti-androgens as flutamide. The effects on the reproductive axis depend on the stage of development and the window of exposure, as well as the dose and the compound. The wide distribution of EDC into the environment affects both human health and ecosystems in general, the study of their mechanisms of action is extremely important currently.
胎儿期和出生后发育过程中的不同干扰会引发内分泌适应性变化,这些变化会永久性地改变新陈代谢,增加日后患疾病的易感性,这一过程被称为“发育编程”。内分泌干扰化合物(EDC)在环境中广泛传播,具有雌激素、抗雌激素或抗雄激素活性;它们具有亲脂性,可在脂肪组织中长期储存。孕期和哺乳期母亲接触EDC会通过胎盘和母乳使胎儿和新生儿暴露。流行病学和实验研究表明,宫内和/或新生儿期接触EDC会导致生殖系统改变。己烯雌酚(DES)是记录最详尽的化合物,这种合成雌激素在20世纪50年代和60年代被用于孕妇以预防流产。它与子宫内接触的儿童泌尿生殖系统异常有关,并已退出市场。“DES女儿”患阴道发育不全、自然流产、早产、子宫畸形、月经异常和低生育率的发生率较高。“DES儿子”表现出睾丸发育不全综合征,其特征为尿道下裂、隐睾和精液质量低下。该病症也与胎儿接触氟他胺等抗雄激素有关。对生殖轴的影响取决于发育阶段、暴露窗口期、剂量和化合物。EDC在环境中的广泛分布总体上影响人类健康和生态系统,目前对其作用机制的研究极其重要。