Oxidative stress as a mediator of environmental exposure impacts on fertility endpoints

了解不孕症的起源是环境健康研究的一个重要领域，因为它影响了很大一部分人口，并导致沉重的治疗经济负担和心理压力。查明化学品接触情况和毒物作用的基本机制可能有助于预防这些后果。尿邻苯二甲酸酯代谢物与男性生育力不良相关，包括精液质量参数，如精子计数、形态和活力，以及精子DNA完整性。此外，邻苯二甲酸酯与不孕夫妇的男性和女性的体外受精（IVF）结果有关。在该文献中观察到的最强相关性是男性邻苯二甲酸酯暴露与精液质量下降和精子DNA损伤增加之间，以及不孕女性邻苯二甲酸酯暴露与IVF结局较差（包括卵母细胞产量、临床妊娠和活产）之间。我们假设氧化应激是邻苯二甲酸酯可能对生育力和IVF成功产生不利影响的重要机制。 为了调查这个问题，本研究使用了来自环境与生殖健康（EARTH）研究的数据，该研究是一项持续的前瞻性队列研究，始于2004年，在美国马萨诸塞州波士顿的马萨诸塞州总医院（MGH）进行。在该人群中，招募正在进行中，生育力指标包括卵母细胞产量和窦卵泡计数，将检查其与女性氧化应激浓度的关系，以及生育力和妊娠结局（卵母细胞产量、窦卵泡计数、着床、妊娠丢失和活产），将检查其与男性和女性氧化应激水平的关系。此外，我们将研究邻苯二甲酸酯暴露与生育力和妊娠终点之间观察到的氧化应激相关性的中介作用。 去年的进展 在过去的一年里，我们已经完成了尿液氧化应激生物标志物的分析，并开始进行统计分析，以解决我们的主要研究问题。一份文件正在修订中，另一份正在编写中。

Understanding the origins of infertility is an important area of environmental health research, as it impacts a substantial proportion of the population and leads to heavy economic burden of treatment and psychological stress. Identifying chemical exposures and underlying mechanisms of toxicant action may enable prevention of these consequences. Urinary phthalate metabolites have been associated with poor fertility outcomes in men, including semen quality parameters such as sperm count, morphology, and motility, as well as sperm DNA integrity. Further, phthalates have been linked to adverse in vitro fertilization (IVF) outcomes in men and women from infertile couples. The strongest associations observed in this body of literature are between phthalate exposure in men and decline in semen quality and increased sperm DNA damage, and between phthalate exposure in infertile women and poorer IVF outcomes (including oocyte yield, clinical pregnancy, and live birth). We hypothesize that oxidative stress is an important mechanism by which phthalates may adversely impact fertility and IVF success. To investigate this question, this study uses data from the Environment and Reproductive Health (EARTH) study, an ongoing prospective cohort begun in 2004 of couples seeking fertility treatment, conducted at Massachusetts General Hospital (MGH) in Boston, MA, USA. In this population recruitment is ongoing, and fertility measures include oocyte yield and antral follicle count, which will be examined in relation to female oxidative stress concentrations, and fertility and pregnancy outcomes (oocyte yield, antral follicle count, implantation, pregnancy loss, and live birth) which will be examined in relation to both male and female oxidative stress levels. In addition, we will investigate mediation of the observed associations between phthalate exposure and fertility and pregnancy endpoints by oxidative stress. Last years progress Over the past year we have completed analysis of urinary oxidative stress biomarkers and have begun statistical analyses to address our primary research questions. One paper is under revision and another is in progress.