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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。

Effects of Endocrine-Disrupting Chemicals on Endometrial Receptivity and Embryo Implantation: A Systematic Review of 34 Mouse Model Studies.

机构信息

Gynecology Division, Department of Medical and Surgical Sciences and Translational Medicine, Sant'Andrea University Hospital, Sapienza University of Rome, Via di Grottarossa 1035, 00189 Rome, Italy.

PhD Program in "Translational Medicine and Oncology", Department of Medical and Surgical Sciences and Translational Medicine, Psychology and Medicine Faculty, Sapienza University of Rome, Via di Grottarossa 1035, 00189 Rome, Italy.

出版信息

Int J Environ Res Public Health. 2021 Jun 25;18(13):6840. doi: 10.3390/ijerph18136840.

Abstract

Several available studies have already analyzed the systemic effects of endocrine-disrupting chemicals (EDCs) on fertile woman and neonatal outcomes, but little is still known in humans about the precise mechanisms of interference of these compounds with the endometrial receptivity. There is consistent evidence that continuous and prolonged exposure to EDCs is a risk factor for reduced fertility and fecundity in women. Preliminary studies on mammalian models provide robust evidence about this issue and could help gynecologists worldwide to prevent long term injury caused by EDCs on human fertility. In this systematic review, we aimed to systematically summarize all available data about EDC effects on blastocyst endometrial implantation. We performed a systematic review using PubMed/MEDLINE to summarize all in vivo studies, carried out on mice models, analyzing the molecular consequences of the prolonged exposure of EDC on the implantation process. 34 studies carried out on mouse models were included. Primary effects of EDC were a reduction of the number of implantation sites and pregnancy rates, particularly after BPA and phthalate exposure. Furthermore, the endometrial expression of estrogen (ER) and progesterone receptors (PR), as well as their activation pathways, is compromised after EDC exposure. Finally, the expression of the primary endometrial markers of receptivity (such as MUC1, HOXA10, Inn and E-cadherin) after EDC contact was analyzed. In conclusion EDC deeply affect blastocyst implantation in mouse model. Several players of the implantation mechanism are strongly influenced by the exposure to different categories of EDC.

摘要

已有多项研究分析了内分泌干扰化学物质(EDCs)对育龄妇女和新生儿结局的系统影响,但人类对这些化合物干扰子宫内膜容受性的确切机制仍知之甚少。有确凿证据表明,持续和长期暴露于 EDC 是导致女性生育力和受孕力下降的一个危险因素。哺乳动物模型的初步研究为此提供了有力证据,可帮助全球妇科医生预防 EDC 对人类生育力造成的长期损害。在本次系统评价中,我们旨在系统总结所有关于 EDC 对胚泡子宫内膜植入影响的现有数据。我们使用 PubMed/MEDLINE 进行了系统评价,以总结所有在小鼠模型上进行的体内研究,分析 EDC 长期暴露对植入过程的分子后果。共纳入 34 项在小鼠模型上进行的研究。EDC 的主要作用是减少着床部位数量和妊娠率,尤其是在 BPA 和邻苯二甲酸酯暴露后。此外,EDC 暴露后,雌激素(ER)和孕激素受体(PR)及其激活途径的子宫内膜表达受到损害。最后,分析了 EDC 接触后主要子宫内膜容受性标志物(如 MUC1、HOXA10、Inn 和 E-钙黏蛋白)的表达。总之,EDC 严重影响了小鼠模型中的胚泡着床。着床机制的几个参与者受到不同类别 EDC 暴露的强烈影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95b2/8297133/1909dbea2b00/ijerph-18-06840-g001.jpg

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