Bisphenol A alters early oogenesis and follicle formation in the fetal ovary of the rhesus monkey
Bisphenol A alters early oogenesis and follicle formation in the fetal ovary of the rhesus monkey
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DOI：
10.1073/pnas.1207854109
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发表时间：
2012-10-23
影响因子：
11.1
通讯作者：
VandeVoort, Catherine A.
中科院分区：
文献类型：
--
作者：
Hunt, Patricia A.;Lawson, Crystal;VandeVoort, Catherine A.
在消费品中广泛使用干扰内分泌的化学物质双酚A (BPA)，导致人类几乎持续暴露于该物质中。据报道，在啮齿类动物中，低剂量暴露会对卵巢发育中的两个不同阶段产生不利影响：胎儿卵巢减数分裂开始时的前期事件和围产期卵巢卵泡形成。由于这些影响可能会影响暴露个体的生殖寿命和成功，我们在恒河猴身上进行了研究，以确定BPA是否会在灵长类动物的卵巢发育中引起类似的干扰。人类接触的途径和程度尚不清楚；因此，采用了两种不同的暴露方案：每日单次口服剂量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，与小鼠一样，BPA在减数分裂第一次分裂时为染色体分离奠定基础的前期事件中引起了微妙的干扰。我们对在卵泡形成期间暴露于每日单次口服剂量的妊娠晚期胎儿的分析显示，多卵细胞卵泡的增加与在啮齿动物中报道的类似。然而，在持续暴露的动物中，有两种独特的表型是明显的：髓质区域持续的未封闭卵母细胞和次级和窦卵泡中小的，不生长的卵母细胞。由于对卵子发生的两个阶段的影响都是在使用与人类相似的BPA循环水平的剂量时产生的，这些发现引起了对人类生殖健康的关注。
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.