Calhoun Kathryn C, Padilla-Banks Elizabeth, Jefferson Wendy N, Liu Liwen, Gerrish Kevin E, Young Steven L, Wood Charles E, Hunt Patricia A, Vandevoort Catherine A, Williams Carmen J
Reproductive Medicine Group, Laboratory of Reproductive & Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America ; Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, United States of America.
Reproductive Medicine Group, Laboratory of Reproductive & Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America.
PLoS One. 2014 Jan 23;9(1):e85894. doi: 10.1371/journal.pone.0085894. eCollection 2014.
Bisphenol A (BPA) exposure results in numerous developmental and functional abnormalities in reproductive organs in rodent models, but limited data are available regarding BPA effects in the primate uterus. To determine if maternal oral BPA exposure affects fetal uterine development in a non-human primate model, pregnant rhesus macaques carrying female fetuses were exposed orally to 400 µg/kg BPA or vehicle control daily from gestation day (GD) 50-100 or GD100-165. Fetal uteri were collected at the completion of treatment (GD100 or GD165); tissue histology, cell proliferation, and expression of estrogen receptor alpha (ERα) and progesterone receptor (PR) were compared to that of controls. Gene expression analysis was conducted using rhesus macaque microarrays. There were no significant differences in histology or in the percentage of cells expressing the proliferation marker Ki-67, ERα, or PR in BPA-exposed uteri compared to controls at GD100 or GD165. Minimal differences in gene expression were observed between BPA-exposed and control GD100 uteri. However, at GD165, BPA-exposed uteri had significant differences in gene expression compared to controls. Several of the altered genes, including HOXA13, WNT4, and WNT5A, are critical for reproductive organ development and/or adult function. We conclude that second or third trimester BPA exposure does not significantly affect fetal uterus development based on morphological, proliferation, and steroid hormone receptor assessments. However, differences in expression of key developmental genes after third trimester exposure suggest that BPA could alter transcriptional signals influencing uterine function later in life.
在啮齿动物模型中，双酚A（BPA）暴露会导致生殖器官出现众多发育和功能异常，但关于BPA对灵长类动物子宫影响的数据有限。为了确定母体经口暴露于BPA是否会影响非人类灵长类动物模型中胎儿子宫的发育，从妊娠第50 - 100天或第100 - 165天，每天给怀有雌性胎儿的怀孕恒河猴经口给予400μg/kg BPA或载体对照。在治疗结束时（妊娠第100天或第165天）收集胎儿子宫；将组织组织学、细胞增殖以及雌激素受体α（ERα）和孕激素受体（PR）的表达与对照组进行比较。使用恒河猴微阵列进行基因表达分析。在妊娠第100天或第165天，与对照组相比，暴露于BPA的子宫在组织学或表达增殖标志物Ki - 67、ERα或PR的细胞百分比方面没有显著差异。在暴露于BPA的妊娠第100天子宫和对照子宫之间观察到基因表达的微小差异。然而，在妊娠第165天，暴露于BPA的子宫与对照组相比在基因表达上有显著差异。一些改变的基因，包括HOXA13、WNT4和WNT5A，对生殖器官发育和/或成年功能至关重要。我们得出结论，基于形态学、增殖和类固醇激素受体评估，妊娠中期或晚期暴露于BPA不会显著影响胎儿子宫发育。然而，妊娠晚期暴露后关键发育基因表达的差异表明，BPA可能会改变影响生命后期子宫功能的转录信号。
