Environmental influence on reproductive tract function

不同的环境化学品可以影响各种生物的生殖能力，这取决于暴露的时间和剂量，并且被认为也会影响人类生殖。 一个例子是植物雌激素，染料木黄酮，当给予新生雌性小鼠时，对它们的繁殖能力有长期影响。然而，他们不育的根本原因尚不清楚。 我们正在使用新生儿金雀异黄素不育模型，以确定雌激素化合物如何影响女性生殖道发育和功能，以及这些化合物如何影响胚胎发育的女性生殖道内通过植入的时间。这些研究与人类生育能力有关，因为在食用大豆婴儿配方奶粉的婴儿中测量到的染料木黄酮水平与我们的小鼠模型中达到的水平相似。 用植物雌激素金雀异黄素治疗的雌性小鼠由于输卵管中胚胎发育的缺陷和植入的缺陷而不育。 在过去的一年中，我们进行了一系列的实验，以确定输卵管异常的特征。我们发现了形态学的显著改变和已知调节女性生殖道发育的因子的基因表达模式的永久改变。 这项工作发表在《环境健康展望》上。我们还发现异常的输卵管环境导致胚泡发育异常，这可能是输卵管粘膜对妊娠的免疫反应改变的结果;然而，这些异常并不妨碍胚胎移植后的成功发育。这些研究将继续进行。 有证据表明，在啮齿动物产前暴露于环境相关剂量的双酚A（BPA）会导致卵巢和女性生殖道发育异常。 尽管啮齿动物研究引起了对人类暴露于BPA的担忧，但关于BPA对人类或非人类灵长类动物模型发育影响的信息很少。 帕特里夏·亨特博士（华盛顿州立大学）和Cathi VandeVoort博士（加州大学戴维斯分校灵长类动物中心）发起了一项研究，以检查母体在妊娠第二或第三个三个月期间暴露于BPA对雌性恒河猴胎儿发育的影响。 使用2种不同的BPA给药策略处理猴子，并收集所有组织。我们正在评估女性生殖道的形态和基因表达。该项目将生成发育正常的恒河猴输卵管和子宫的基因表达谱，并提供证据证明当比较对照组和BPA处理组时，基因表达谱和组织学是否存在差异。

Different environmental chemicals can affect the reproductive capability of a variety of organisms, depending on the timing and dose of exposure, and are thought to impact human reproduction as well. One example is the phytoestrogen, genistein, which when given to neonatal female mice has long-term effects on their ability to reproduce. The underlying causes of their infertility, however, are not known. We are using the neonatal genistein model of infertility to determine how estrogenic compounds affect female reproductive tract development and function, and how these compounds influence embryo development within the female reproductive tract through the time of implantation. These studies are relevant to human fertility because genistein levels similar to those reached in our mouse model are measured in babies on soy-based infant formula. Female mice treated neonatally with the phytoestrogen genistein are infertile because of deficiencies in embryo development in the oviduct and defects in implantation. During the past year we performed a series of experiments to characterize the abnormalities in the oviduct. We found significant alterations in morphology and permanently altered patterns of gene expression of factors known to modulate female reproductive tract development. This work was published in Environmental Health Perspectives. We also found that the abnormal oviduct environment causes abnormalities in blastocyst development that are likely a consequence of alterations in the oviduct mucosal immune response to pregnancy; however, these abnormalities do not preclude successful term development after embryo transfer. These studies will be continued. There is evidence in rodents that prenatal exposure to environmentally relevant doses of bisphenol A (BPA) causes abnormal ovarian and female reproductive tract development. Although the rodent studies have raised concerns regarding human exposure to BPA, there is minimal information regarding the effects of BPA on development in humans or non-human primate models. Dr. Patricia Hunt (Washington State Univ.) and Dr. Cathi VandeVoort (UC Davis Primate Center) initiated a study to examine the effects of maternal BPA exposure during either the 2nd or 3rd trimesters of pregnancy on development of female Rhesus monkey fetuses. The monkeys were treated using 2 different BPA dosing strategies, and all tissues have been collected. We are evaluating the morphology and gene expression in the female reproductive tract. This project will generate a gene expression profile of developing normal Rhesus monkey oviduct and uterus, and also provide evidence regarding whether there are differences in the gene expression profiles and histology when comparing control and BPA-treated groups.