LaPlante Charlotte D, Catanese Mary C, Bansal Ruby, Vandenberg Laura N
Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts-Amherst, Amherst, Massachusetts 01003.
Graduate Program in Neuroscience and Behavior, University of Massachusetts-Amherst, Amherst, Massachusetts 01003.
Endocrinology. 2017 Oct 1;158(10):3448-3461. doi: 10.1210/en.2017-00437.
High doses of estrogenic pharmaceuticals were once prescribed to women to halt lactation. Yet, the effects of low-level xenoestrogens on lactation remain poorly studied. We investigated the effects of bisphenol S (BPS), an estrogen receptor (ER) agonist, on the lactating mammary gland; the arcuate nucleus, a region of the hypothalamus important for neuroendocrine control of lactational behaviors; and nursing behavior in CD-1 mice. Female mice were exposed to vehicle, 2 or 200 µg BPS/kg/d from pregnancy day 9 until lactational day (LD) 20, and tissues were collected on LD21. Tissues were also collected from a second group at LD2. BPS exposure significantly reduced the fraction of the mammary gland comprised of lobules, the milk-producing units, on LD21, but not LD2. BPS also altered expression of Esr1 and ERα in the mammary gland at LD21, consistent with early involution. In the arcuate nucleus, no changes were observed in expression of signal transducer and activator of transcription 5, a marker of prolactin signaling, or ERα, suggesting that BPS may act directly on the mammary gland. However, observations of nursing behavior collected during the lactational period revealed stage-specific effects on both pup and maternal nursing behaviors; BPS-treated dams spent significantly more time nursing later in the lactational period, and BPS-treated pups were less likely to initiate nursing. Pup growth and development were also stunted. These data indicate that low doses of BPS can alter lactational behaviors and the maternal mammary gland. Together, they support the hypothesis that pregnancy and lactation are sensitive to low-dose xenoestrogen exposures.
曾经，高剂量的雌激素类药物被用于给女性回奶。然而，低水平的外源性雌激素对泌乳的影响仍未得到充分研究。我们研究了雌激素受体（ER）激动剂双酚S（BPS）对哺乳期乳腺、下丘脑弓状核（对泌乳行为的神经内分泌控制很重要的一个区域）以及CD-1小鼠的哺乳行为的影响。从妊娠第9天到泌乳第20天，雌性小鼠每天分别接受赋形剂、2 μg或200 μg BPS/kg的处理，并在泌乳第21天收集组织。还在泌乳第2天从第二组收集组织。BPS暴露显著降低了泌乳第21天乳腺中由小叶（产奶单位）组成的部分的比例，但在泌乳第2天没有影响。BPS还改变了泌乳第21天乳腺中Esr1和ERα的表达，这与早期退化一致。在弓状核中，催乳素信号标志物转录信号转导子和激活子5或ERα的表达没有变化，这表明BPS可能直接作用于乳腺。然而，对哺乳期收集的哺乳行为的观察揭示了对幼崽和母鼠哺乳行为的阶段特异性影响；接受BPS处理的母鼠在哺乳期后期花费显著更多时间哺乳，而接受BPS处理的幼崽开始哺乳的可能性较小。幼崽的生长和发育也受到阻碍。这些数据表明，低剂量的BPS可以改变泌乳行为和母鼠的乳腺。总之，它们支持了妊娠和泌乳对低剂量外源性雌激素暴露敏感的假说。
