Developmental exposures to bisphenol S, a BPA replacement, alter estrogen-responsiveness of the female reproductive tract: A pilot study ABOUT THE AUTHORS

Abstract: Developmental exposures to bisphenol A (BPA), an estrogen receptor agonist, can disrupt development of the female reproductive tract in rodents and non-human primates. Due to an increased public knowledge of negative health effects associated with BPA exposure, BPA has begun to be phased out of many consumer products and in some cases it has been replaced with structurally similar compounds including bisphenol S (BPS). This study examined CD-1 mice exposed to a low dose of BPS during early development (200 μg/kg/day from gestational day 8 until postnatal day 19). BPS altered expression of estrogen-responsive genes in both the uterus and ovary, and induced increases in ovarian follicular development in pre-pubertal females evaluated at postnatal day 22. Prior studies have revealed that developmental exposures to environmental chemicals including BPA alter the response of animals to hormonal or carcinogen challenges experienced later in life. To evaluate whether early life exposures to BPS alter responses of females to an estrogen challenge, additional females were exposed to ethinyl estradiol from ABOUT THE AUTHORS The Vandenberg laboratory is interested in understanding how environmental factors can influence the development of estrogen-sensitive organs, using mice as a model organism. In particular, we are interested in a class of chemicals termed "endocrine disruptors". Prior work has established that developing creatures are sensitive to hormones, and thus can be affected by even low doses of endocrine disruptors. Our work aims to understand how organs such as the mammary gland, uterus, ovary and brain are affected by estrogenic compounds, which periods in development are sensitive to exposures, whether the effects of these chemicals represent adverse health outcomes, and the mechanisms by which these compounds act at low doses. This work represents a pilot study we developed in collaboration with the Suvorov laboratory to examine the effects of bisphenol S (BPS), an environmental contaminant that is raising recent public health concern. Other publications from our groups have demonstrated that BPS alters maternal behavior, the maternal brain, body weight in offspring, and offspring social behaviors. PUBLIC INTEREST STATEMENT Bisphenol S (BPS) is a chemical that is used in numerous consumer products and is used as a replacement for BPA, a known endocrine disruptor. Concern over BPA, BPS, and other similar chemicals has been raised because of tests showing that these compounds can mimic the actions of estrogen and other hormones. This study examined the effects of exposures to low doses of BPS during gestation and early postnatal development using mice as a model organism. Female mice exposed to BPS showed modest changes in the development of female reproductive organs including the ovary and uterus. Yet, when these females were given an additional dose of estrogen, pushing them to enter puberty earlier, animals exposed to BPS responded abnormally. Their ovaries were under-responsive to estrogen, and their uteri were over-responsive. These results raise concerns about the endocrine disrupting properties of BPS and its potential to affect human reproductive health. postnatal day 19 through postnatal day 21. BPS-treated females responded abnormally to this estrogen challenge, displaying heightened responses in the uterus and diminished responses in the ovary. Although additional studies are needed to characterize the mechanisms by which BPS alters the female reproductive tract, this pilot study provides evidence that a common BPA replacement chemical may have endocrine disrupting properties

Developmental exposures to bisphenol S, a BPA replacement, alter estrogen-responsiveness of the female reproductive tract: A pilot study

<p>Developmental exposures to bisphenol A (BPA), an estrogen receptor agonist, can disrupt development of the female reproductive tract in rodents and non-human primates. Due to an increased public knowledge of negative health effects associated with BPA exposure, BPA has begun to be phased out of many consumer products and in some cases it has been replaced with structurally similar compounds including bisphenol S (BPS). This study examined CD-1 mice exposed to a low dose of BPS during early development (200 μg/kg/day from gestational day 8 until postnatal day 19). BPS altered expression of estrogen-responsive genes in both the uterus and ovary, and induced increases in ovarian follicular development in pre-pubertal females evaluated at postnatal day 22. Prior studies have revealed that developmental exposures to environmental chemicals including BPA alter the response of animals to hormonal or carcinogen challenges experienced later in life. To evaluate whether early life exposures to BPS alter responses of females to an estrogen challenge, additional females were exposed to ethinyl estradiol from postnatal day 19 through postnatal day 21. BPS-treated females responded abnormally to this estrogen challenge, displaying heightened responses in the uterus and diminished responses in the ovary. Although additional studies are needed to characterize the mechanisms by which BPS alters the female reproductive tract, this pilot study provides evidence that a common BPA replacement chemical may have endocrine disrupting properties.</p

FGF21 Signals to Glutamatergic Neurons in the Ventromedial Hypothalamus to Suppress Carbohydrate Intake

Fibroblast growth factor 21 (FGF21) is an endocrine hormone produced by the liver that regulates nutrient and metabolic homeostasis. FGF21 production is increased in response to macronutrient imbalance and signals to the brain to suppress sugar intake and sweet-taste preference. However, the central targets mediating these effects have been unclear. Here, we identify FGF21 target cells in the hypothalamus and reveal that FGF21 signaling to glutamatergic neurons is both necessary and sufficient to mediate FGF21-induced sugar suppression and sweet-taste preference. Moreover, we show that FGF21 acts directly in the ventromedial hypothalamus (VMH) to specifically regulate sucrose intake but not non-nutritive sweet-taste preference, body weight or energy expenditure. Finally, our data demonstrates that FGF21 affects neuronal activity by increasing activation and excitability of neurons in the VMH. Thus, FGF21 signaling to glutamatergic neurons in the VMH is an important component of the neurocircuitry that functions to regulate sucrose intake