Cheryl Rosenfeld

Cheryl Rosenfeld

Professor

About

221
Publications
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7,474
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Publications

Publications (221)
Article
Full-text available
In mice, the fetal brain is dependent upon the placenta for factors that guide its early development. This linkage between the two organs has given rise to the term, the placenta–brain axis. A similar interrelationship between the two organs may exist in humans. We hypothesize that extracellular vesicles (EVs) released from placental trophoblast (T...
Article
Pregnant women are often prescribed or abuse opioid drugs. The placenta is likely the key to understanding how opioids cause adverse pregnancy outcomes. Maternal oxycodone (OXY) exposure of pregnant mice leads to disturbances in the layer of invasive parietal trophoblast giant cells (pTGC) that forms the interface between the placenta and uterus. T...
Article
Full-text available
Declining estrogen (E2) leads to physical inactivity and adipose tissue (AT) dysfunction. Mechanisms are not fully understood, but E2’s effects on dopamine (DA) activity in the nucleus accumbens (NAc) brain region may mediate changes in mood and voluntary physical activity (PA). Our prior work revealed that loss of E2 robustly affected NAc DA-relat...
Article
Full-text available
Background: The European Food Safety Authority (EFSA) recommended lowering their estimated tolerable daily intake (TDI) for bisphenol A (BPA) 20,000-fold to 0.2 ng/kg body weight (BW)/day. BPA is an extensively studied high production volume endocrine disrupting chemical (EDC) associated with a vast array of diseases. Prior risk assessments of BPA...
Article
Full-text available
The fetal brain of the mouse is thought to be dependent upon the placenta as a source of serotonin (5-hydroxytryptamine; 5-HT) and other factors. How factors reach the developing brain remains uncertain but are postulated here to be part of the cargo carried by placental extracellular vesicles (EV). We have analyzed the protein, catecholamine, and...
Article
Full-text available
Opioid drugs are commonly prescribed analgesic to pregnant women. Direct exposure to such drugs may slow gut motility, alter gut permeability, and affect the gut microbiome. While such drugs affect gut microbiome in infants, no study to date has determined whether developmental exposure to such drugs results in longstanding effects on gut microbiot...
Article
Opioid drugs are analgesics increasingly being prescribed to control pain associated with a wide range of causes. Usage of pregnant women has dramatically increased in the past decades. Neonates born to these women are at risk for neonatal abstinence syndrome (NAS, also referred termed neonatal opioid withdrawal syndrome, NOWS). Negative birth outc...
Article
Full-text available
Bisphenol A (BPA) is an endocrine-disrupting chemical (EDC) that is used in a wide-variety of plastic and common house-hold items. Therefore, there is potential continual exposure to this compound. BPA exposure has been linked to certain placenta-associated obstetric complications such as preeclampsia, fetal growth restriction, miscarriage, and pre...
Article
Full-text available
Bisphenol-A (BPA) and bisphenol-S (BPS) are endocrine disrupting chemicals (EDCs) found primarily in plastics. Estrogen is a primary hormonal regulator of skeletal growth and development; however, the impact of gestational BPA or BPS exposure on skeletal health of offspring remains relatively unknown. Here, adult female mice were randomized into th...
Article
The aim of this study was to determine small RNA expression changes in mouse placenta induced by bisphenol A (BPA) exposure. The methods included exposing female mice to BPA two weeks prior to conception through gestational day 12.5; whereupon fetal placentas were collected, frozen in liquid nitrogen and stored at -80°C. Small RNAs were isolated an...
Article
Endocrine disrupting chemicals, such as bisphenol A (BPA) and ethinylestradiol (EE2), are detected in the marine environment from plastic waste and wastewater effluent. However, their impact on reproduction in sexually labile coral reef fish is unknown. The objective of this study was to determine impacts of environmentally relevant concentrations...
Article
Endocrine disrupting chemicals (EDCs) mimic natural hormones in the body, but they are not subject to normal homeostatic regulatory mechanisms. One such EDC that is particularly important in animal and human health is bisphenol A (BPA) that is an industrial chemical used to harden plastic, and thus, it is prevalent in many common household items. N...
Article
Introduction The mouse placenta accumulates and possibly produces serotonin (5-hydroxytryptamine; 5-HT) in parietal trophoblast giant cells (pTGC) located at the interface between the placenta and maternal deciduum. However, the roles of 5-HT in placental function are unclear. This lack of information is unfortunate, given that selective serotonin-...
Article
Full-text available
Bisphenol-A (BPA) and bisphenol-S (BPS) are estrogen disrupting chemicals (EDCs) found in the environment and common household items. Estrogen is a primary hormonal regulator of bone growth and development; however, the impact of gestational BPA or BPS exposure on skeletal health of offspring remains relatively unknown. In this longitudinal study,...
Article
Full-text available
The conceptus is most vulnerable to developmental perturbation during its early stages when the events that create functional organ systems are being launched. As the placenta is in direct contact with maternal tissues, it readily encounters any xenobiotics in her bloodstream. Besides serving as a conduit for solutes and waste, the placenta possess...
Article
Histone proteins undergo various modifications that alter chromatin structure, including addition of methyl groups. Enhancer of homolog 2 (EZH2), is a histone methyltransferase that methylates lysine residue 27, and thereby, suppresses gene expression. EZH2 plays integral role in the uterus and other reproductive organs. We have previously shown th...
Article
Full-text available
Opioid drugs are increasingly being prescribed to pregnant women. Such compounds can also bind and activate opioid receptors in the fetal brain, which could lead to long-term brain and behavioral disruptions. We hypothesized that maternal treatment with oxycodone (OXY), the primary opioid at the center of the current crisis, leads to later neurobeh...
Article
Endocrine disrupting chemicals (EDCs) that act as xenoestrogens are natural and synthetic chemicals widely present in food products, industrial products, and the environment. Such compounds can activate or inhibit normal hormonal pathways by binding to steroid and non-steroid receptors. It is becomingly apparent that resident bacteria in the gut an...
Article
Full-text available
Due to their antimicrobial properties, silver nanoparticles (AgNPs) are used in a wide range of consumer products that includes topical wound dressings, coatings for biomedical devices, and food-packaging to extend the shelf-life. Despite their beneficial antimicrobial effects, developmental exposure to such AgNPs may lead to gut dysbiosis and long...
Article
Developmental exposure to endocrine disrupting chemicals (EDCs), e.g., bisphenol A (BPA) or genistein (GEN), causes longstanding epigenome effects. MicroRNAs (miRs) regulate which mRNAs will be translated to proteins and thereby serve as the final checkpoint in epigenetic control. Scant amount is known, however, whether EDCs affect neural miRNA (mi...
Chapter
Vocalizations are an important means for communication within and between all kinds of species. The previous chapters have shown that across species, vocalizations and forms of communications are unique to a given species, from insects to humans. However, there are commonalities in the neuroendocrine mechanisms governing such behavioral responses....
Chapter
The preceding chapters have revealed the complexity and complex neuroendocrine control of vocalization across animal species. The intricate hormonal regulation of vocalizations also renders this behavior susceptible to endocrine-disrupting chemicals that are mass produced and widely prevalent in the environment. Many of these can bind and activate...
Chapter
The preceding chapters have established that across taxa, neuroendocrine mechanisms are essential in regulating vocalization and a variety of other behaviors and systems. Consequently, all these tightly regulated systems are vulnerable to endocrine-disrupting chemicals (EDCs) in the environment. Given the abundance of evidence establishing that suc...
Preprint
Full-text available
Due to their antimicrobial properties, silver nanoparticles (NPs) are used in a wide range of consumer products that includes topical wound dressings, coatings for biomedical devices, and food-packaging to extend the shelf-life. Despite their beneficial antimicrobial effects, developmental exposure to such NPs may lead to gut dysbiosis and long-ter...
Article
Full-text available
Epigenetic modifications regulate normal physiological, as well as pathological processes in various organs, including the uterus and placenta. Both organs undergo dramatic and rapid restructuring that depends upon precise orchestration of events. Epigenetic changes that alter transcription and translation of gene-sets regulate such responses. Hist...
Article
Introduction Pregnant women are increasingly being prescribed and abusing opioid drugs. As the primary communication organ between mother and conceptus, the placenta may be vulnerable to opioid effects but also holds the key to better understanding how these drugs affect long-term offspring health. We hypothesized that maternal treatment with oxyco...
Article
Full-text available
Xenoestrogens are chemicals found in plant products, such as genistein (GEN), and in industrial chemicals, e.g., bisphenol A (BPA), present in plastics and other products that are prevalent in the environment. Early exposure to such endocrine disrupting chemicals (EDC) may affect brain development by directly disrupting neural programming and/or th...
Article
“Consortium Linking Academic and Regulatory Insights on BPA Toxicity” (CLARITY-BPA) was a comprehensive “industry-standard” Good Laboratory Practice (GLP)-compliant 2-year chronic exposure study of bisphenol A (BPA) toxicity that was supplemented by hypothesis-driven independent investigator-initiated studies. The investigator-initiated studies wer...
Article
The hypothalamus and hippocampus are sensitive to early exposure to endocrine disrupting chemicals (EDC). Two EDC that have raised particular concern include bisphenol A (BPA), a widely prevalent chemical in many common household items, and genistein (GEN), a phytoestrogen present in soy and other plants. We hypothesized that early exposure to BPA...
Article
All mammalian species depend on the placenta, a transient organ, for exchange of gases, nutrients, and waste between the mother and conceptus. Besides serving as a conduit for such exchanges, the placenta produces hormones and other factors that influence maternal physiology and fetal development. To meet all of these adaptations, the placenta has...
Article
Full-text available
Placental trophoblast cells are potentially at risk from circulating endocrine-disrupting chemicals, such as bisphenol A (BPA). To understand how BPA and the reputedly more inert bisphenol S (BPS) affect the placenta, C57BL6J mouse dams were fed 200 μg/kg body weight BPA or BPS daily for 2 wk and then bred. They continued to receive these chemicals...
Article
Full-text available
Aromatase catalyzes conversion of testosterone to estradiol and is expressed in a variety of tissues, including the brain. Suppression of aromatase adversely affects metabolism and physical activity behavior, but mechanisms remain uncertain. The hypothesis tested herein was that whole body aromatase deletion would cause gene expression changes in t...
Article
Enhancer of homolog 2 (EZH2) is a histone methyltransferase that suppresses gene expression. Previously, we developed a conditional null model where EZH2 is knocked out in uterus. Deletion of uterine EZH2 increased proliferation of luminal and glandular epithelial cells. Gene expression changes likely underpin these histopathological effects. Herei...
Article
The placenta is a transient organ but essential for the survival of all mammalian species by allowing for the exchanges of gasses, nutrients, and waste between maternal and fetal placenta. In rodents and humans with a hemochorial placenta, fetal placenta cells are susceptible to pharmaceutical agents and other compounds, as they are bathed directly...
Article
Full-text available
The underlying neurological events accompanying dog domestication remain elusive. To reconstruct the domestication process in an experimental setting, silver foxes (Vulpes vulpes) have been deliberately bred for tame vs aggressive behaviors for more than 50 generations at the Institute for Cytology and Genetics in Novosibirsk, Russia. The hypothala...
Article
Full-text available
Many pregnant and nursing women consume high amounts of soy and other plant products that contain phytoestrogens, such as genistein (GEN) and daidzein. Infants may also be provided soy based formulas. With their ability to bind and activate estrogen receptors (ESR) in the brain, such compounds can disrupt normal brain programming and lead to later...
Article
Human offspring encounter high amounts of phytoestrogens, such as genistein (GEN), through maternal diet and soy-based formulas. Such chemicals can exert estrogenic activity and thereby disrupt neurobehavioral programming. Besides inducing direct host effects, GEN might cause gut dysbiosis and alter gut metabolites. To determine whether exposure to...
Article
Both membrane and nuclear fractions of estrogen receptor 1 (ESR1) mediate 17β-estradiol (E2) actions. Mice expressing nuclear (n)ESR1 but lacking membrane (m)ESR1 (nuclear-only estrogen receptor 1 [NOER] mice) show reduced E2 responsivity and reproductive abnormalities culminating in adult male and female infertility. Using this model, we investiga...
Article
Both membrane and nuclear fractions of estrogen receptor 1 (ESR1) mediate 17β‐estradiol (E2) actions. Mice expressing nuclear (n)ESR1 but lacking membrane (m)ESR1 (nuclear‐only estrogen receptor 1 [NOER] mice) show reduced E2 responsivity and reproductive abnormalities culminating in adult male and female infertility. Using this model, we investiga...
Article
How dogs became domesticated and the underlying neurological events that accompanied this process continues to fascinate scientists. To recapitulate what this domestication process may have entailed, silver foxes ( Vulpes vulpes ) have been deliberately bred for tame vs. aggressive behaviors for greater than 50 generations at the Institute for Cyto...
Article
Full-text available
Vitamin D is an essential nutrient that is metabolized in the body to generate an active metabolite (1,25(OH)2D) with hormone-like activity and highly diverse roles in cellular function. Vitamin D deficiency (VDD) is a prevalent but easily preventable nutritional disturbance. Emerging evidence demonstrates the importance of sufficient vitamin D con...
Article
Full-text available
Background Brain sexual differentiation is sculpted by precise coordination of steroid hormones during development. Programming of several brain regions in males depends upon aromatase conversion of testosterone to estrogen. However, it is not clear the direct contribution that Y chromosome associated genes, especially sex-determining region Y (Sry...
Article
Phytoestrogens, such as daidzein and genistein, may be used to treat various hormone-dependent disorders. Daidzein can be metabolized by intestinal microbes to S-equol. However, not all individuals possess bacteria producing this metabolite, resulting in categorization of equol vs nonequol producers. Past human and rodent studies have suggested tha...
Article
Full-text available
Abstract Phytoestrogens are plant-derived compounds found in a variety of foods, most notably, soy. These compounds have been shown to improve immuno-metabolic health, yet mechanisms remain uncertain. We demonstrated previously that dietary phytoestrogen-rich soy (SOY) rescued metabolic dysfunction/inflammation following ovariectomy (OVX) in female...
Article
Full-text available
Estrogen binding to estrogen receptors (ESR) triggers signaling cascades within cells. Historically, a major emphasis has been characterizing estrogen-induced genomic actions resulting from binding to nuclear estrogen receptor 1 (nESR1). However, recent evidence indicates the first receptors estrogens encounter as they enter a cell, membrane ESR1 (...
Article
Full-text available
Diverse cognitive functions in many vertebrate species are influenced by local conversion of androgens to 17β-estradiol (E2) by aromatase. This enzyme is highly expressed in various brain regions across species, with some inter-species variation in terms of regional brain expression. Since women with breast cancer and men and women with other disor...
Article
Full-text available
Aromatase is the enzyme responsible for converting testosterone to estradiol. In mammals, aromatase is expressed in the testes, ovaries, brain, and other tissues. While estrogen is traditionally associated with reproduction and sexual behavior in females, our current understanding broadens this perspective to include such biological functions as me...
Article
Full-text available
Bisphenol A (BPA), an endocrine disrupting chemical (EDC), is a ubiquitous pollutant. As part of the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA), we sought to determine whether exposure of Sprague-Dawley rats to 2,500 μg/kg/day BPA (BPA) or 0.5 μg/kg/day ethinyl estradiol (EE) from gestational day 6 through pos...
Article
Full-text available
Rodent pups use vocalizations to communicate with one or both parents in biparental species, such as California mice (Peromyscus californicus). Previous studies have shown California mice developmentally exposed to endocrine disrupting chemicals, bisphenol A (BPA) or ethinyl estradiol (EE), demonstrate later compromised parental behaviors. Reductio...
Data
Median frequency calculation. A) Spectrogram showing one syllable. B) Points in the spectrogram that are above the noise level (background noise + 3 standard deviations). C) Histogram of frequencies are shown in the middle figure. The median of this distribution is the syllable’s “median frequency” and is demarcated by an "X". (TIF)
Data
Circadian effects on total number of phrases by F2 pups. Error bars represent SEM. (TIF)
Data
Diagram of the general experimental design and split plot in space analyses. The “split plot in space” refers to the fact that the vocalization data for each pup are nested together under the dam and sire, which controls for potential litter effects. The “time” portion considers the fact that the pup vocalization responses were repeatedly measured...
Data
Number of pups in parentheses latched onto dam prior to audio recordings in the morning and afternoon on each trial day. Total number of pups for which data were collected are listed in parentheses. (DOCX)
Article
Full-text available
Bisphenol A (BPA) is a pervasive industrial chemical used in many common household items. To examine how early exposure to BPA and ethinyl estradiol (EE, estrogen in birth control pill) might affect biparental care, effects of these chemicals in male and female California mice (Peromyscus californicus), who are monogamous and biparental, were exami...
Article
Paternal environment can induce detrimental developmental origins of health and disease (DOHaD) effects in resulting offspring and even future descendants. Such paternal-induced DOHaD effects might originate from alterations in a possible seminal fluid microbiome (SFM) and composite metabolome. Seminal vesicles secrete a slightly basic product enri...
Article
Full-text available
Purpose: Maternal vitamin D deficiency during pregnancy is a widespread issue that may have long-lasting consequences on offspring adiposity. We sought to determine how maternal vitamin D deficiency during the perinatal period would affect offspring adipose tissue development and gene expression. Methods: Female C57BL/6 J mice were fed either a...
Article
The use of animal models in vitamin D deficiency (VDD) research, particularly in regard to maternal deficits, has increased dramatically, yet these studies may be confounded due to ill-conceived experimental timelines. We conducted 2 experiments to (1) characterize the time course of VDD induction and repletion and (2) explore the long-term consequ...
Article
Full-text available
Brain sexual differentiation is orchestrated by precise coordination of sex steroid hormones. In some species, programming of select male brain regions is dependent upon aromatization of testosterone to estrogen. In mammals, these hormones surge during the organizational and activational periods that occur during perinatal development and adulthood...
Article
Full-text available
Sexual differentiation across taxa may be due to genetic sex determination (GSD) and/or temperature sex determination (TSD). In many mammals, males are heterogametic (XY); whereas females are homogametic (XX). In most birds, the opposite is the case with females being heterogametic (ZW) and males the homogametic sex (ZZ). Many reptile species lack...
Data
Male and female Australian Brush-turkeys. Comparison of example breeding male (Panels A and B) with an example breeding female (C and D) reveals that when the male is in full breeding mode, his wattle enlarges and become bright red in color. However, the female wattle, which is smaller, remains the same color and size from season to season. Females...
Data
Diagram of all the potential mechanisms that can result in skewing of primary sex ratio in Australian Brush-turkeys. A) As the sex-determining parent, females can selectively lay Z- or W-bearing eggs. She can also alter in a sex-dependent manner the amount of yolk proteins, hormones, or other nutritional factors within the egg. B) The male can affe...
Article
Full-text available
The gut microbiome consists of over 10³–10⁴ microorganism inhabitants that together possess 150 times more genes that the human genome and thus should be considered an “organ” in of itself. Such communities of bacteria are in dynamic flux and susceptible to changes in host environment and body condition. In turn, gut microbiome disturbances can aff...
Preprint
Full-text available
Due to their antimicrobial properties, silver nanoparticles (AgNPs) are being used in non-edible and edible consumer products. It is not clear though if exposure to these chemicals can exert toxic effects on the host and gut microbiome. Conflicting studies have been reported on whether AgNPs result in gut dysbiosis and other changes within the host...
Article
Animal and human studies provide evidence that exposure to the endocrine disrupting chemical (EDC), bisphenol A (BPA), can lead to neurobehavioral disorders. Consequently, there is an impetus to identify safer alternatives to BPA. Three bisphenol compounds proposed as potential safer alternatives to BPA are bisphenol S (BPS), bisphenol F (BPF), and...
Article
Full-text available
The fetal period represents an important window of susceptibility for later obesity and metabolic disease. Maternal vitamin D deficiency (VDD) during pregnancy is a global concern that may have long-lasting consequences on offspring metabolic health. We sought to determine whether a VDD in utero environment affects fetal adipose tissue development...