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父体暴露于非必需重金属会影响卵胞浆内单精子注射(ICSI)周期中的胚胎卵裂和着床:一种矛盾效应的证据。

Paternal Exposure to Non-essential Heavy Metal Affects Embryo Cleavage and Implantation in Intracytoplasmic Sperm Injection (ICSI) Cycles: Evidence for a Paradoxical Effect.

机构信息

Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon.

Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon.

出版信息

Reprod Sci. 2021 Sep;28(9):2550-2561. doi: 10.1007/s43032-021-00510-9. Epub 2021 Mar 8.

DOI:10.1007/s43032-021-00510-9
PMID:33683670
Abstract

Although the adverse effects of non-essential heavy metals on semen quality have been demonstrated in experimental animal models and occupational human exposure studies, little is known about the reproductive efficiency of exposed sperm during the process of intracytoplasmic sperm injection (ICSI). Our study aims to evaluate the effect of paternal exposure to non-essential heavy metals on embryo efficiency outcomes (embryo cleavage, fragmentation, implantation, and live birth) in ICSI cycle. Ninety-five heterosexual couples who underwent 95 ICSI cycles and 78 fresh embryo transfers between January 2003 and December 2009 were evaluated. Men whose female partner was undergoing ICSI were asked to provide semen and blood samples. Heavy metal levels (Pb, Cd, As, Hg, Ba, and U) were analyzed using an ion-coupled plasma-mass spectrometry (ICP-MS; Agilent 7500 ce, Agilent Technologies, Germany) equipped with a cell dynamic range (CDR). Paternal exposure to trace heavy metals was found to influence intermediate reproductive endpoints in ICSI cycles. After adjusting for paternal and maternal confounders, paternal blood concentrations of Cd [-0.30(-0.11,-0.02)], As [-0.26(-0.16,-0.11)], and U [-0.22(-0.24,-0.02)] were inversely associated with embryo cell cleavage on day 3. Counterintuitively, paternal blood and semen Pb levels [0.26(0.01,0.22); 0.25(0.03,0.14)] as well as semen U levels [0.27(0.01,0.19)] were positively associated with the proportion of implanted embryos. There were no significant associations observed for clinical pregnancy and live birth rates with any paternal heavy metal concentrations in semen and blood. These findings highlight the importance of paternal health for embryo efficiency outcomes in ICSI treatment cycles and the need for more male partner inclusive counseling in fertility practice. They also underline a paradoxical positive association between some heavy metal pollutants at low exposure levels and reproductive outcomes.

摘要

虽然实验动物模型和职业性人体暴露研究已经证实了非必需重金属对精液质量的不良影响,但对于 ICSI 过程中暴露精子的生殖效率知之甚少。我们的研究旨在评估父体暴露于非必需重金属对 ICSI 周期胚胎效率结局(胚胎卵裂、碎片、着床和活产)的影响。2003 年 1 月至 2009 年 12 月期间,对 95 对接受 95 个 ICSI 周期和 78 个新鲜胚胎移植的异性恋夫妇进行了评估。接受 ICSI 的女性伴侣的男性被要求提供精液和血液样本。使用配备有细胞动态范围 (CDR) 的离子耦合等离子体质谱仪 (ICP-MS; Agilent 7500 ce,Agilent Technologies,德国) 分析重金属水平 (Pb、Cd、As、Hg、Ba 和 U)。研究发现,父体暴露于痕量重金属会影响 ICSI 周期中的中间生殖终点。在校正了父体和母体混杂因素后,父体血液中 Cd 的浓度[-0.30(-0.11,-0.02)]、As [-0.26(-0.16,-0.11)]和 U [-0.22(-0.24,-0.02)]与第 3 天胚胎细胞卵裂呈负相关。相反,父体血液和精液 Pb 水平[0.26(0.01,0.22); 0.25(0.03,0.14)]以及精液 U 水平[0.27(0.01,0.19)]与着床胚胎的比例呈正相关。在精液和血液中任何父体重金属浓度方面,都没有观察到与临床妊娠和活产率有显著关联。这些发现强调了父体健康对 ICSI 治疗周期中胚胎效率结局的重要性,以及在生育实践中需要更多包括男性伴侣在内的咨询。它们还强调了在低暴露水平下某些重金属污染物与生殖结局之间存在矛盾的正相关关系。

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