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[内分泌干扰化合物及其在生殖轴发育编程中的作用]

[Endocrine disruptor compounds and their role in the developmental programming of the reproductive axis].

作者信息

Guzmán Carolina, Zambrano Elena

机构信息

Departamento de Biologia de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirin, Tlalpan, México.

出版信息

Rev Invest Clin. 2007 Jan-Feb;59(1):73-81.

PMID:17569302
Abstract

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 It was implicated in urogenital abnormalities in children exposed in utero and was withdrawn from the market.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.

摘要

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。

相似文献

1
[Endocrine disruptor compounds and their role in the developmental programming of the reproductive axis].[内分泌干扰化合物及其在生殖轴发育编程中的作用]
Rev Invest Clin. 2007 Jan-Feb;59(1):73-81.
2
[Fertility disorders attributable to the use of diethylstilbestrol during intrauterine life].[宫内生活期间使用己烯雌酚所致的生育障碍]
Rev Fr Gynecol Obstet. 1984 Apr;79(4):297-300, 303-5.
3
Environmental anti-androgens and male reproductive health: focus on phthalates and testicular dysgenesis syndrome.环境抗雄激素与男性生殖健康:聚焦邻苯二甲酸盐与睾丸发育不全综合征
Reproduction. 2004 Mar;127(3):305-15. doi: 10.1530/rep.1.00025.
4
DES exposure: implications for childbearing.己烯雌酚暴露:对生育的影响
Int J Childbirth Educ. 1992 Nov-Dec;7(4):21-8.
5
[The concept of endocrine disruption and human health].[内分泌干扰与人类健康的概念]
Med Sci (Paris). 2007 Feb;23(2):198-204. doi: 10.1051/medsci/2007232198.
6
Lessons learned from perinatal exposure to diethylstilbestrol.围产期接触己烯雌酚的经验教训。
Toxicol Appl Pharmacol. 2004 Sep 1;199(2):142-50. doi: 10.1016/j.taap.2003.11.033.
7
The mitochondrial-dependent pathway is chronically affected in testicular germ cell death in adult rats exposed in utero to anti-androgens.在子宫内暴露于抗雄激素的成年大鼠中,线粒体依赖性途径在睾丸生殖细胞死亡中受到长期影响。
J Endocrinol. 2004 Oct;183(1):79-90. doi: 10.1677/joe.1.05771.
8
Endocrine disrupting chemicals: effects on human male reproductive health.内分泌干扰化学物质:对人类男性生殖健康的影响
Early Pregnancy (Cherry Hill). 2001 Apr;5(2):80-112.
9
Diethylstilbestrol in pregnancy: an update.孕期己烯雌酚:最新情况
Can Med Assoc J. 1982 Nov 1;127(9):812-3.
10
Structural changes of the genital tract associated with in utero exposure to diethylstilbestrol.与子宫内暴露于己烯雌酚相关的生殖道结构变化。
Obstet Gynecol Annu. 1982;11:187-202.

引用本文的文献

1
Are the Effects of DES Over? A Tragic Lesson from the Past.DES 的影响已经结束了吗?一个来自过去的悲剧教训。
Int J Environ Res Public Health. 2021 Sep 30;18(19):10309. doi: 10.3390/ijerph181910309.
2
Effects of Endocrine-Disrupting Chemicals on Endometrial Receptivity and Embryo Implantation: A Systematic Review of 34 Mouse Model Studies.内分泌干扰物对子宫内膜容受性和胚胎着床的影响:34 项小鼠模型研究的系统评价。
Int J Environ Res Public Health. 2021 Jun 25;18(13):6840. doi: 10.3390/ijerph18136840.
3
Impact of Di-2-Ethylhexyl Phthalate Metabolites on Male Reproductive Function: a Systematic Review of Human Evidence.
邻苯二甲酸二(2-乙基)己酯代谢物对男性生殖功能的影响:系统评价人类证据。
Curr Environ Health Rep. 2018 Mar;5(1):20-33. doi: 10.1007/s40572-018-0174-3.
4
Exogenous hormonal regulation in breast cancer cells by phytoestrogens and endocrine disruptors.植物雌激素和内分泌干扰物对乳腺癌细胞的外源性激素调节。
Curr Med Chem. 2014;21(9):1129-45. doi: 10.2174/09298673113206660291.