Environmental Endocrine Disruptors and Human Sperm Chromosomal Abnormalities

描述（由调查者提供）：在美国，每年有超过200万对想要孩子的夫妇不孕，超过200万的怀孕在怀孕20周之前就失去了概念。大约40%的人类不育病例是由男性因素引起的。在减数分裂过程中，染色体分离的错误导致结构畸变和染色体数目的不平衡，称为非整倍体。在后代中发现的大多数新基因突变和性染色体数量的大多数异常都来自父亲的精子。越来越多的证据表明，环境化学物质可能通过内分泌激素调节机制对精子发生和染色体畸变产生不利影响。拟议的研究是高效和经济的，因为它将利用现有的医学访谈数据和存档的生物标本来调查精子非整倍体与常见环境暴露之间的新关系，特别是多氯联苯（PCBs）、滴滴涕、有机磷（OPs）和拟除虫菊酯（PYRs）。存档的精液、血清和尿液样本来自500名曾在一家大型医院生育诊所接受生育能力评估的男性。多氯联苯、滴滴涕、OPs和pyr的暴露在这一人群中已经有了很好的特征，我们小组之前的工作已经发现了有机氯和劣等精液质量以及当代使用的农药和DNA损伤之间的联系。问题仍然是这些暴露是否会影响精子的非整倍体。我们已经验证了一种自动化系统，该系统可以在大样本量中量化精子非整倍体，从而可以研究存档样本的完整补充，并可以量化精子非整倍体与常见环境暴露之间的新关系。本研究还将通过探索非整倍体与DNA损伤和精液质量的常见指标的可比性，更充分地表征非整倍体作为一种有效的生物标志物。

DESCRIPTION (provided by investigator): Each year more than 2 million couples in the US who want to have children are infertile, and over 2 million conceptions are lost before the twentieth week of gestation. About 40 percent of cases of human infertility are due to male factors. Errors in chromosome segregation during meiosis result in structural aberrations and imbalances in chromosome number known as aneuploidy. Most new gene mutations seen in offspring and most abnormalities in the numbers of the sex chromosomes arise from the father's sperm. There is emerging evidence that environmental chemicals can adversely affect spermatogenesis and the occurrence of chromosomal aberrations, possibly through mechanisms of endocrine hormone modulation. The proposed study is efficient and economic in that it will leverage existing medical interview data and archived biological specimens to investigate novel relationships between sperm aneuploidy and common environmental exposures, specifically polychlorinated biphenyls (PCBs), DDT, organophosphates (OPs), and pyrethroids (PYRs). Archived semen, serum, and urine samples are available from 500 men who have attended a large hospital based fertility clinic for fertility evaluation. Exposures to PCBs, DDT, OPs and PYRs have been well characterized in this population, and prior work from our group has found associations between organochlorines and inferior semen quality and contemporary use pesticides and DNA damage. The question remains as to whether these exposures impact sperm aneuploidy. We have validated an automated system that makes quantifying sperm aneuploidy in large sample sizes feasible so that the full complement of archived samples can be studied and novel relationships between sperm aneuploidy and common environmental exposures can be quantified. This study will also more fully characterize aneuploidy as an effect biomarker by exploring its comparability with DNA damage and common indicators of semen quality. PUBLIC HEALTH RELEVANCE: Environmental chemicals that are common in today's environment may be having an impact on male reproductive health. This study investigates whether chemicals common in our daily environment can affect male fertility and potential risks for birth defects.