School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, WA 99164, USA.
Proc Natl Acad Sci U S A. 2012 Oct 23;109(43):17525-30. doi: 10.1073/pnas.1207854109. Epub 2012 Sep 24.
Widespread use of the endocrine disrupting chemical bisphenol A (BPA) in consumer products has resulted in nearly continuous human exposure. In rodents, low-dose exposures have been reported to adversely affect two distinct stages of oogenesis in the developing ovary: the events of prophase at the onset of meiosis in the fetal ovary and the formation of follicles in the perinatal ovary. Because these effects could influence the reproductive longevity and success of the exposed individual, we conducted studies in the rhesus monkey to determine whether BPA induces similar disturbances in the developing primate ovary. The routes and levels of human exposure are unclear; hence, two different exposure protocols were used: single daily oral doses and continuous exposure via subdermal implant. Our analyses of second trimester fetuses exposed at the time of meiotic onset suggest that, as in mice, BPA induces subtle disturbances in the prophase events that set the stage for chromosome segregation at the first meiotic division. Our analyses of third-trimester fetuses exposed to single daily oral doses during the time of follicle formation revealed an increase in multioocyte follicles analogous to that reported in rodents. However, two unique phenotypes were evident in continuously exposed animals: persistent unenclosed oocytes in the medullary region and small, nongrowing oocytes in secondary and antral follicles. Because effects on both stages of oogenesis were elicited using doses that yield circulating levels of BPA analogous to those reported in humans, these findings raise concerns for human reproductive health.
广泛使用内分泌干扰化学物质双酚 A（BPA）在消费产品中导致了几乎连续的人类暴露。在啮齿动物中，低剂量暴露已被报道对发育中的卵巢中两个不同的卵母细胞发生阶段产生不利影响：减数分裂开始时的前期事件和围产期卵巢中卵泡的形成。由于这些影响可能会影响暴露个体的生殖寿命和成功，我们在恒河猴中进行了研究，以确定 BPA 是否会在发育中的灵长类动物卵巢中引起类似的干扰。人类暴露的途径和水平尚不清楚；因此，使用了两种不同的暴露方案：每日口服一次和通过皮下植入持续暴露。我们对在减数分裂开始时暴露的妊娠中期胎儿的分析表明，与在小鼠中一样，BPA 会导致前期事件的细微干扰，这些事件为第一次减数分裂中的染色体分离奠定了基础。我们对在卵泡形成期间接受每日口服一次剂量暴露的妊娠晚期胎儿的分析显示，多卵母细胞卵泡的增加类似于在啮齿动物中报道的情况。然而，在连续暴露的动物中出现了两种独特的表型：在髓质区域中持续存在未封闭的卵母细胞和在次级和腔前卵泡中体积小且不生长的卵母细胞。由于使用类似于在人类中报道的循环 BPA 水平产生的剂量诱发了卵母细胞发生的两个阶段的影响，这些发现引起了对人类生殖健康的关注。
