Bisphenol S Alters the Lactating Mammary Gland and Nursing Behaviors in Mice Exposed During Pregnancy and Lactation

Abstract

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.

Bisphenol S in Food Causes Hormonal and Obesogenic Effects Comparable to or Worse than Bisphenol A: A Literature Review

“…In a 2017 article, mice were exposed to BPS during pregnancy and for the first 20 days of lactation. The mice showed normal mammary gland physiology at lactational day 2 (LD2), but at LD21, there was a significant decrease in the number of milk-producing lobules [18]. In the same year, another study was performed that included a study of the maternal behavior of mice after BPS exposure during pregnancy and lactation.…”

The developmental basis of disease: Update on environmental exposures and animal models

“…Alonso‐Magdalena et al showed that BPA exposure during pregnancy in mice led to decreased insulin secretion, altered glucose tolerance and increased weight gain in the dam several months post‐partum indicating a predisposition to type 2 diabetes and obesity. In another model, La Plante et al showed that pregnant mice exposed to bisphenol S (an analogue of BPA) through postnatal day 20 showed that the mammary gland had less milk producing units along with altered nursing behaviour leading to stunted pup growth and development. These data have been confirmed in humans which showed that perfluorinated chemicals during pregnancy reduced the duration of breastfeeding .…”

Endocrine Disruptors: Very Low Doses with Genuinely High Impacts on Male Reproduction

“…Translactational exposure, another way of indirect influence with environmental agents, is a reason of changes of male reproduction after lactating female mice were exposed to BPA [93]. Moreover, this type of exposure to bisphenols creates a risk of changed nursing behavior and also affects the mammary glands of mothers [94].…”