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

了解不孕不育的起源是环境卫生研究的一个重要领域，因为它影响到相当大比例的人口，并导致沉重的治疗经济负担和心理压力。查明化学品暴露和潜在的毒物作用机制可能有助于预防这些后果。尿邻苯二甲酸盐代谢产物与男性生育不良结局有关，包括精液质量参数，如精子数量、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体外受精(IVF)不良结局有关。在这篇文献中观察到的最强相关性是男性接触邻苯二甲酸盐与精液质量下降和精子DNA损伤增加之间，以及不孕不育女性接触邻苯二甲酸盐与较差的试管受精结果(包括卵子产量、临床妊娠和活产)之间的关系。我们假设氧化应激是邻苯二甲酸盐可能对生育和试管受精成功产生不利影响的一个重要机制。 为了研究这个问题，这项研究使用了环境与生殖健康(地球)研究的数据，该研究于2004年开始对寻求生育治疗的夫妇进行前瞻性队列研究，该研究在美国马萨诸塞州波士顿的马萨诸塞州综合医院(MGH)进行。在这一人群中，招募正在进行中，生育措施包括卵子产量和窦卵泡数，这将与女性氧化应激浓度进行检查，以及生育力和怀孕结果(卵母细胞产量、有腔卵泡数、着床、妊娠损失和活产)将与男性和女性的氧化应激水平进行检查。此外，我们还将研究氧化应激在邻苯二甲酸盐暴露与生育和妊娠终点之间的调节作用。 过去几年取得的进展 在过去的一年里，我们发表了关于男性和女性氧化应激水平与体外受精和人工授精结局之间的关联的结果。此外，我们还准备了一份手稿，研究研究人群中与氧化应激措施相关的尿邻苯二甲酸盐代谢物的混合物。

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 published results on the associations between male and female oxidative stress levels in association IVF and IUI outcomes. Additionally, we have prepared a manuscript examining mixtures of urinary phthalate metabolites in association with oxidative stress measures in the study population.