Environmental Endocrine Disruptors and Human Sperm Chromosomal Abnormalities

描述（由研究者提供）：美国每年有超过200万对想要孩子的夫妇不育，超过200万的怀孕在怀孕20周之前丢失。大约40%的人类不育症是由于男性因素造成的。减数分裂期间染色体分离的错误导致结构畸变和染色体数目的不平衡，称为非整倍性。在后代中发现的大多数新的基因突变和大多数性染色体数量的异常都来自父亲的精子。有新的证据表明，环境化学品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。拟议的研究是有效和经济的，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性和常见的环境暴露之间的新关系，特别是多氯联苯（PCB），滴滴涕，有机磷（OP）和拟除虫菊酯（PYR）。存档的精液，血清和尿液样本来自500名男性，他们参加了一家大型医院的生育诊所进行生育评估。暴露于多氯联苯，滴滴涕，OP和PYR已在这一人群中得到很好的表征，我们小组先前的工作已经发现有机氯与精液质量低劣以及当代使用杀虫剂和DNA损伤之间的关联。问题是这些暴露是否会影响精子的非整倍性。我们已经验证了一个自动化系统，使量化精子非整倍体在大样本量可行，使存档样本的完整补充可以研究和精子非整倍体和常见的环境暴露之间的新关系可以量化。本研究还将通过探索非整倍体与DNA损伤和精液质量常见指标的可比性，更全面地表征非整倍体作为效应生物标志物。 公共卫生相关性：当今环境中常见的环境化学品可能会对男性生殖健康产生影响。这项研究调查了我们日常环境中常见的化学物质是否会影响男性生育能力和出生缺陷的潜在风险。

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.