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  1. Article ; Online: The influence of estrogen response element ERα signaling in the control of feeding behaviors in male and female mice.

    Yasrebi, Ali / Regan, Daniel / Roepke, Troy A

    Steroids

    2023  Volume 195, Page(s) 109228

    Abstract: Circulating 17β-estradiol (E2) controls energy homeostasis and feeding behaviors primarily by its nuclear receptor, estrogen receptor (ER) α. As such, it is important to understand the role of ERα signaling in the neuroendocrine control of feeding. Our ... ...

    Abstract Circulating 17β-estradiol (E2) controls energy homeostasis and feeding behaviors primarily by its nuclear receptor, estrogen receptor (ER) α. As such, it is important to understand the role of ERα signaling in the neuroendocrine control of feeding. Our previous data indicated that the loss of ERα signaling through estrogen response elements (ERE) alters food intake in a female mouse model. Hence, we hypothesize that ERE-dependent ERα is necessary for typical feeding behaviors in mice. To test this hypothesis, we examined feeding behaviors on low-fat diet (LFD) and high-fat diet (HFD) in three mouse strains: total ERα knockout (KO), ERα knockin/knockout (KIKO), which lack a functional DNA-binding domain, and their wild type (WT) C57 littermates comparing intact males and females and ovariectomized females with or without E2 replacement. All feeding behaviors were recorded using the Biological Data Acquisition monitoring system (Research Diets). In intact male mice, KO and KIKO consumed less than WT mice on LFD and HFD, while in intact female mice, KIKO consumed less than WT and KO. These differences were primarily driven by shorter meal duration in the KO and KIKO. In ovariectomized females, E2-treated WT and KIKO consumed more LFD than KO driven in part by an increase in meal frequency and a decrease in meal size. On HFD, WT consumed more than KO with E2, again due to effects on meal size and frequency. Collectively, these suggest that both ERE-dependent and -independent ERα signaling are involved in feeding behaviors in female mice depending on the diet consumed.
    MeSH term(s) Mice ; Female ; Male ; Animals ; Estrogen Receptor alpha/genetics ; Receptors, Estrogen ; Mice, Knockout ; Estrogens ; Feeding Behavior ; Response Elements
    Chemical Substances Estrogen Receptor alpha ; Receptors, Estrogen ; Estrogens
    Language English
    Publishing date 2023-03-27
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 80312-1
    ISSN 1878-5867 ; 0039-128X
    ISSN (online) 1878-5867
    ISSN 0039-128X
    DOI 10.1016/j.steroids.2023.109228
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Beyond the Binary: Gender Inclusivity in Schizophrenia Research.

    Nolan, Caitlin J / Roepke, Troy A / Perreault, Melissa L

    Biological psychiatry

    2023  Volume 94, Issue 7, Page(s) 543–549

    Abstract: Schizophrenia is a severe neuropsychiatric disorder with significant differences in the incidence and symptomology between cisgender men and women. In recent years, considerably more attention has been on the inclusion of sex and gender in schizophrenia ... ...

    Abstract Schizophrenia is a severe neuropsychiatric disorder with significant differences in the incidence and symptomology between cisgender men and women. In recent years, considerably more attention has been on the inclusion of sex and gender in schizophrenia research. However, the majority of this research has failed to consider gender outside of the socially constructed binary of men and women. As a result, little is known about schizophrenia in transgender and gender-nonconforming populations. In this review, we present evidence showing that transgender and gender-nonconforming individuals have elevated risk of developing schizophrenia, and we discuss minority stress theory and other potential factors that may contribute to this risk. The need for inclusion of transgender and gender-nonconforming communities in schizophrenia research is emphasized, alongside a discussion on considerations and challenges associated with this type of research. Finally, we offer specific strategies to make research on schizophrenia, and research on other neuropsychiatric disorders, more inclusive of those populations that do not fall within the socially constructed gender binary. If we are to succeed in the development of more personalized therapeutic approaches for all, a better understanding of the variability of the human brain is needed.
    MeSH term(s) Male ; Humans ; Female ; Schizophrenia ; Gender Identity ; Transgender Persons/psychology
    Language English
    Publishing date 2023-03-31
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 209434-4
    ISSN 1873-2402 ; 0006-3223
    ISSN (online) 1873-2402
    ISSN 0006-3223
    DOI 10.1016/j.biopsych.2023.03.018
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  3. Article ; Online: REPRODUCTIVE TOXICOLOGY: Impact of endocrine disruptors on neurons expressing GnRH or kisspeptin and pituitary gonadotropins.

    Roepke, Troy A / Sadlier, Nicole C

    Reproduction (Cambridge, England)

    2021  Volume 162, Issue 5, Page(s) F131–F145

    Abstract: Reproduction is a complex process that is controlled centrally via a network of hypothalamic neurons to modulate the pulsatile release of gonadotropin-releasing hormone (GnRH) and subsequently pituitary gonadotropins. The gonadotropins, luteinizing ... ...

    Abstract Reproduction is a complex process that is controlled centrally via a network of hypothalamic neurons to modulate the pulsatile release of gonadotropin-releasing hormone (GnRH) and subsequently pituitary gonadotropins. The gonadotropins, luteinizing hormone, and follicle-stimulating hormone, drive gametogenesis and hormone production from the gonads. The hypothalamic-pituitary exchange is controlled by gonadal steroids through negative and positive feedback mechanisms via steroid receptors. Due to the expression of these receptors, GnRH neurons, the hypothalamic neurons that control them, and pituitary gonadotropes are sensitive to exogenous compounds that interact with steroid and nuclear receptors or alter hormone production and metabolism. The compounds, called endocrine-disrupting compounds (EDCs), are ubiquitous and persistent in human environments and could bioaccumulate in the body. EDCs include plasticizers (like bisphenol A), dioxin, polychlorinated biphenyls (PCBs), organochlorine pesticides, flame retardants, and perfluorinated alkyl substances (PFAS). Numerous studies have reported that perinatal, juvenile, or adult exposure to these EDCs, primarily in rats, disrupt the hypothalamic control of pituitary gonadotropin production leading to disruption of gonadal steroid production and estrous cyclicity. The purpose of this review is to evaluate these studies primarily focusing on GnRH and kisspeptin neurons and anterior pituitary gonadotropins and to discuss the need for deeper investigations into the hypothalamic-pituitary-gonadal axis.
    MeSH term(s) Animals ; Endocrine Disruptors/toxicity ; Female ; Gonadotropin-Releasing Hormone/metabolism ; Gonadotropins ; Gonadotropins, Pituitary ; Kisspeptins ; Neurons/metabolism ; Pregnancy ; Rats ; Reproduction
    Chemical Substances Endocrine Disruptors ; Gonadotropins ; Gonadotropins, Pituitary ; Kisspeptins ; Gonadotropin-Releasing Hormone (33515-09-2)
    Language English
    Publishing date 2021-10-05
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 2034501-X
    ISSN 1741-7899 ; 1470-1626 ; 1476-3990
    ISSN (online) 1741-7899
    ISSN 1470-1626 ; 1476-3990
    DOI 10.1530/REP-20-0612
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Chronic stress-induced synaptic changes to corticotropin-releasing factor-signaling in the bed nucleus of the stria terminalis.

    Maita, Isabella / Roepke, Troy A / Samuels, Benjamin A

    Frontiers in behavioral neuroscience

    2022  Volume 16, Page(s) 903782

    Abstract: The sexually dimorphic bed nucleus of the stria terminalis (BNST) is comprised of several distinct regions, some of which act as a hub for stress-induced changes in neural circuitry and behavior. In rodents, the anterodorsal BNST is especially affected ... ...

    Abstract The sexually dimorphic bed nucleus of the stria terminalis (BNST) is comprised of several distinct regions, some of which act as a hub for stress-induced changes in neural circuitry and behavior. In rodents, the anterodorsal BNST is especially affected by chronic exposure to stress, which results in alterations to the corticotropin-releasing factor (CRF)-signaling pathway, including CRF receptors and upstream regulators. Stress increases cellular excitability in BNST CRF+ neurons by potentiating miniature excitatory postsynaptic current (mEPSC) amplitude, altering the resting membrane potential, and diminishing M-currents (a voltage-gated K+ current that stabilizes membrane potential). Rodent anterodorsal and anterolateral BNST neurons are also critical regulators of behavior, including avoidance of aversive contexts and fear learning (especially that of sustained threats). These rodent behaviors are historically associated with anxiety. Furthermore, BNST is implicated in stress-related mood disorders, including anxiety and Post-Traumatic Stress Disorders in humans, and may be linked to sex differences found in mood disorders.
    Language English
    Publishing date 2022-08-02
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2452960-6
    ISSN 1662-5153
    ISSN 1662-5153
    DOI 10.3389/fnbeh.2022.903782
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  5. Article ; Online: Challenges and inclusive practices for LGBTQIA2S+ scientists in the American Physiological Society.

    Moreira, Jesse D / Bates, Melissa L / Roepke, Troy A

    American journal of physiology. Heart and circulatory physiology

    2022  Volume 323, Issue 1, Page(s) H121–H124

    MeSH term(s) Humans ; Physiology ; Research Personnel ; Sexual and Gender Minorities ; Societies, Medical ; United States
    Language English
    Publishing date 2022-06-10
    Publishing country United States
    Document type Editorial ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 603838-4
    ISSN 1522-1539 ; 0363-6135
    ISSN (online) 1522-1539
    ISSN 0363-6135
    DOI 10.1152/ajpheart.00234.2022
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  6. Article ; Online: Organophosphate Flame Retardants Excite Arcuate Melanocortin Circuitry and Increase Neuronal Sensitivity to Ghrelin in Adult Mice.

    Vail, Gwyndolin M / Roepke, Troy A

    Endocrinology

    2020  Volume 161, Issue 11

    Abstract: Organophosphate flame retardants (OPFRs) are a class of chemicals that have become near ubiquitous in the modern environment. While OPFRs provide valuable protection against flammability of household items, they are increasingly implicated as an ... ...

    Abstract Organophosphate flame retardants (OPFRs) are a class of chemicals that have become near ubiquitous in the modern environment. While OPFRs provide valuable protection against flammability of household items, they are increasingly implicated as an endocrine disrupting chemical (EDC). We previously reported that exposure to a mixture of OPFRs causes sex-dependent disruptions of energy homeostasis through alterations in ingestive behavior and activity in adult mice. Because feeding behavior and energy expenditure are largely coordinated by the hypothalamus, we hypothesized that OPFR disruption of energy homeostasis may occur through EDC action on melanocortin circuitry within the arcuate nucleus. To this end, we exposed male and female transgenic mice expressing green fluorescent protein in either neuropeptide Y (NPY) or proopiomelanocortin (POMC) neurons to a common mixture of OPFRs (triphenyl phosphate, tricresyl phosphate, and tris(1,3-dichloro-2-propyl)phosphate; each 1 mg/kg bodyweight/day) for 4 weeks. We then electrophysiologically examined neuronal properties using whole-cell patch clamp technique. OPFR exposure depolarized the resting membrane of NPY neurons and dampened a hyperpolarizing K+ current known as the M-current within the same neurons from female mice. These neurons were further demonstrated to have increased sensitivity to ghrelin excitation, which more potently reduced the M-current in OPFR-exposed females. POMC neurons from female mice exhibited elevated baseline excitability and are indicated in receiving greater excitatory synaptic input when exposed to OPFRs. Together, these data support a sex-selective effect of OPFRs to increase neuronal output from the melanocortin circuitry governing feeding behavior and energy expenditure, and give reason for further examination of OPFR impact on human health.
    MeSH term(s) Animals ; Arcuate Nucleus of Hypothalamus/drug effects ; Arcuate Nucleus of Hypothalamus/metabolism ; Drug Resistance/drug effects ; Endocrine Disruptors/pharmacology ; Female ; Flame Retardants/pharmacology ; Ghrelin/pharmacology ; Hypothalamus/metabolism ; Male ; Melanocortins/metabolism ; Mice ; Mice, Transgenic ; Nerve Net/drug effects ; Nerve Net/physiology ; Neurons/drug effects ; Neurons/metabolism ; Neuropeptide Y/genetics ; Neuropeptide Y/metabolism ; Organophosphates/pharmacology ; Pro-Opiomelanocortin/genetics ; Pro-Opiomelanocortin/metabolism
    Chemical Substances Endocrine Disruptors ; Flame Retardants ; Ghrelin ; Melanocortins ; Neuropeptide Y ; Organophosphates ; Pro-Opiomelanocortin (66796-54-1)
    Language English
    Publishing date 2020-10-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 427856-2
    ISSN 1945-7170 ; 0013-7227
    ISSN (online) 1945-7170
    ISSN 0013-7227
    DOI 10.1210/endocr/bqaa168
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  7. Article ; Online: 17β-Estradiol Increases Arcuate KNDy Neuronal Sensitivity to Ghrelin Inhibition of the M-Current in Female Mice.

    Conde, Kristie / Roepke, Troy A

    Neuroendocrinology

    2019  Volume 110, Issue 7-8, Page(s) 582–594

    Abstract: Obesity and anorexia result in dysregulation of the hypothalamic-pituitary-gonadal axis, negatively impacting reproduction. Ghrelin, secreted from the stomach, potentially mediates negative energy states and neuroendocrine control of reproduction by ... ...

    Abstract Obesity and anorexia result in dysregulation of the hypothalamic-pituitary-gonadal axis, negatively impacting reproduction. Ghrelin, secreted from the stomach, potentially mediates negative energy states and neuroendocrine control of reproduction by acting through the growth hormone secretagogue receptor (GHSR). GHSR is expressed in hypothalamic arcuate (ARC) Kisspeptin/Neurokinin B (Tac2)/Dynorphin (KNDy) neurons. Ghrelin is known to inhibit the M-current produced by KCNQ channels in other ARC neurons. In addition, we have shown 17β-estradiol (E2) increases Ghsr expression in KNDy neurons 6-fold and increases the M-current in NPY neurons. We hypothesize that E2 increases GHSR expression in KNDy neurons to increase ghrelin sensitivity during negative energy states. Furthermore, we suspect ghrelin targets the M-current in KNDy neurons to control reproduction and energy homeostasis. We utilized ovariectomized Tac2-EGFP adult female mice, pretreated with estradiol benzoate (EB) or oil vehicle and performed whole-cell-patch-clamp recordings to elicit the M-current in KNDy neurons using standard activation protocols in voltage-clamp. Using the selective KCNQ channel blocker XE-991 (40 µM) to target the M-current, oil- and EB-treated mice showed a decrease in the maximum peak current by 75.7 ± 13.8 pA (n = 10) and 68.0 ± 14.7 pA (n = 11), respectively. To determine the actions of ghrelin on the M-current, ghrelin was perfused (100 nM) in oil- and EB-treated mice resulting in the suppression of the maximum peak current by 58.5 ± 15.8 pA (n = 9) and 59.2 ± 11.9 pA (n = 9), respectively. KNDy neurons appeared more sensitive to ghrelin when pretreated with EB, revealing that ARC KNDy neurons are more sensitive to ghrelin during states of high E2.
    MeSH term(s) Animals ; Arcuate Nucleus of Hypothalamus/drug effects ; Arcuate Nucleus of Hypothalamus/physiology ; Dose-Response Relationship, Drug ; Estradiol/pharmacology ; Female ; Ghrelin/metabolism ; Ghrelin/pharmacology ; Membrane Potentials/drug effects ; Membrane Potentials/genetics ; Mice ; Mice, Transgenic ; Neurons/cytology ; Neurons/drug effects ; Neurons/physiology ; Ovariectomy ; Patch-Clamp Techniques ; Protein Precursors/genetics ; Protein Precursors/metabolism ; Tachykinins/genetics ; Tachykinins/metabolism
    Chemical Substances Ghrelin ; Protein Precursors ; Tachykinins ; preprotachykinin ; Estradiol (4TI98Z838E)
    Language English
    Publishing date 2019-09-05
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 123303-8
    ISSN 1423-0194 ; 0028-3835
    ISSN (online) 1423-0194
    ISSN 0028-3835
    DOI 10.1159/000503146
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Importance of survey demographic questions to foster inclusion in medicine and research and reduce health inequities for LGBTQIA2S+ individuals.

    Moreira, Jesse D / Haack, Karla / White, Vee / Bates, Melissa L / Gopal, Deepa M / Roepke, Troy A

    American journal of physiology. Heart and circulatory physiology

    2023  Volume 324, Issue 6, Page(s) H856–H862

    Abstract: A clear, inclusive, and accurate approach to the collection of demographic information in clinical research and medical practice is critical to understanding the healthcare needs of the specific population. Inclusive demography constitutes appropriate ... ...

    Abstract A clear, inclusive, and accurate approach to the collection of demographic information in clinical research and medical practice is critical to understanding the healthcare needs of the specific population. Inclusive demography constitutes appropriate and accurate characterization of an individual's sexual orientation and gender identity (SOGI) data. Appropriate demography fosters sense of inclusion and belonging for those belonging to medically marginalized communities such as the lesbian, gay, bisexual, transgender, queer, intersex, asexual, and Indigenous Two-Spirit (LGBTQIA2S+) communities and improves health outcomes. Acquiring inclusive demographics in healthcare research is needed for the following critical reasons. First, LGBTQIA2S+ individuals experience undue psychological harm when their identities are not appropriately captured in survey data, promoting further alienation of the LGBTQIA2S+ community in medicine and research. Second, LGBTQIA2S+ populations are disproportionately burdened by several major cardiovascular and cardiovascular-associated diseases, including hypertension and diabetes. Failure to include these populations, and accurately characterize their participation, in research leads to failure to identify associations between identities and disease, resulting in worse health outcomes. Furthermore, this lack of precision in current data for sex, gender, and sexual orientation may lead to inaccurate data for all populations, not just the LGBTQIA2S+ community. Finally, there are currently major political and social threats and attacks on the LGBTQIA2S+ community and, in particular, on transgender and gender-diverse individuals. Proper medical inclusion and advocacy for the LGBTQIA2S+ community by the medical community may help protect the community from further undue harm through creating sense of belonging and reductions in marginalization-related health inequities.
    MeSH term(s) Humans ; Female ; Male ; Gender Identity ; Sexual Behavior ; Sexual and Gender Minorities ; Surveys and Questionnaires ; Health Inequities
    Language English
    Publishing date 2023-04-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 603838-4
    ISSN 1522-1539 ; 0363-6135
    ISSN (online) 1522-1539
    ISSN 0363-6135
    DOI 10.1152/ajpheart.00152.2023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Membrane-initiated estrogen signaling via Gq-coupled GPCR in the central nervous system.

    Vail, Gwyndolin / Roepke, Troy A

    Steroids

    2018  Volume 142, Page(s) 77–83

    Abstract: The last few decades have revealed increasing complexity and depth to our knowledge of receptor-mediated estrogen signaling. Nuclear estrogen receptors (ERs) ERα and ERβ remain the fundamental dogma, but recent research targeting membrane-bound ERs urges ...

    Abstract The last few decades have revealed increasing complexity and depth to our knowledge of receptor-mediated estrogen signaling. Nuclear estrogen receptors (ERs) ERα and ERβ remain the fundamental dogma, but recent research targeting membrane-bound ERs urges for a more expanded view on ER signaling. ERα and ERβ are also involved in membrane-delineated signaling alongside membrane-specific G protein-coupled estrogen receptor 1 (GPER1), ER-X, and the Gq-coupled membrane ER (Gq-mER). Membrane ERs are responsible for eliciting rapid responses to estrogen signaling, and their importance has been increasingly indicated in central nervous system (CNS) regulation of such functions as reproduction, energy homeostasis, and stress. While the Gq-mER signaling pathway is well characterized, the receptor structure and gene remains uncharacterized, although it is not similar to the nuclear ERα/β. This review will describe the current knowledge of this putative membrane ER and its selective ligand, STX, from its initial characterization in hypothalamic melanocortin circuitry to recent research exploring its role in the CNS outside of the hypothalamus.
    MeSH term(s) Cell Membrane/metabolism ; Central Nervous System/metabolism ; Estrogens/metabolism ; Humans ; Receptors, Estrogen/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Signal Transduction
    Chemical Substances Estrogens ; GPER1 protein, human ; Receptors, Estrogen ; Receptors, G-Protein-Coupled
    Language English
    Publishing date 2018-01-31
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 80312-1
    ISSN 1878-5867 ; 0039-128X
    ISSN (online) 1878-5867
    ISSN 0039-128X
    DOI 10.1016/j.steroids.2018.01.010
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  10. Article ; Online: Perinatal exposure to bisphenol A at the intersection of stress, anxiety, and depression.

    Wiersielis, Kimberly R / Samuels, Benjamin A / Roepke, Troy A

    Neurotoxicology and teratology

    2020  Volume 79, Page(s) 106884

    Abstract: Endocrine-disrupting compounds (EDCs) are common contaminants in our environment that interfere with typical endocrine function. EDCs can act on steroid and nuclear receptors or alter hormone production. One particular EDC of critical concern is ... ...

    Abstract Endocrine-disrupting compounds (EDCs) are common contaminants in our environment that interfere with typical endocrine function. EDCs can act on steroid and nuclear receptors or alter hormone production. One particular EDC of critical concern is bisphenol A (BPA) due to its potential harm during the perinatal period of development. Previous studies suggest that perinatal exposure to BPA alters several neurotransmitter systems and disrupts behaviors associated with depression and anxiety in the rodent offspring later in life. Thus, dysregulation in neurotransmission may translate to behavioral phenotypes observed in mood and arousal. Many of the systems disrupted by BPA also overlap with the stress system, although little evidence exists on the effects of perinatal BPA exposure in relation to stress and behavior. The purpose of this review is to explore studies involved in perinatal BPA exposure and the stress response at neurochemical and behavioral endpoints. Although more research is needed, we suggest that perinatal BPA exposure is likely inducing variations in behavioral phenotypes that modulate their action through dysregulation of neurotransmitter systems sensitive to stress and endocrine disruption.
    MeSH term(s) Animals ; Anxiety/chemically induced ; Behavior, Animal/drug effects ; Benzhydryl Compounds/toxicity ; Brain/drug effects ; Depression/chemically induced ; Endocrine Disruptors/toxicity ; Endocrine System/drug effects ; Environmental Exposure ; Female ; Humans ; Phenols/toxicity ; Pregnancy ; Prenatal Exposure Delayed Effects/chemically induced ; Prenatal Exposure Delayed Effects/physiopathology ; Prenatal Exposure Delayed Effects/psychology ; Stress, Psychological/chemically induced
    Chemical Substances Benzhydryl Compounds ; Endocrine Disruptors ; Phenols ; bisphenol A (MLT3645I99)
    Language English
    Publishing date 2020-04-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 639165-5
    ISSN 1872-9738 ; 0892-0362
    ISSN (online) 1872-9738
    ISSN 0892-0362
    DOI 10.1016/j.ntt.2020.106884
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