scholarly journals Disruption of Reproductive Aging in Female and Male Rats by Gestational Exposure to Estrogenic Endocrine Disruptors

Endocrinology ◽  
2013 ◽  
Vol 154 (6) ◽  
pp. 2129-2143 ◽  
Author(s):  
Deena M. Walker ◽  
Bailey A. Kermath ◽  
Michael J. Woller ◽  
Andrea C. Gore
Keyword(s):  
Gene Expression ◽  
Median Eminence ◽  
Endocrine Disrupting Chemicals ◽  
Estradiol Benzoate ◽  
Sexually Dimorphic ◽  
Reproductive Aging ◽  
Gestational Exposure ◽  
Hypothalamic Nuclei ◽  
Endocrine Disrupting ◽  
Aroclor 1221

Abstract Polychlorinated biphenyls (PCBs) are industrial contaminants and known endocrine-disrupting chemicals. Previous work has shown that gestational exposure to PCBs cause changes in reproductive neuroendocrine processes. Here we extended work farther down the life spectrum and tested the hypothesis that early life exposure to Aroclor 1221 (A1221), a mixture of primarily estrogenic PCBs, results in sexually dimorphic aging-associated alterations to reproductive parameters in rats, and gene expression changes in hypothalamic nuclei that regulate reproductive function. Pregnant Sprague Dawley rats were injected on gestational days 16 and 18 with vehicle (dimethylsulfoxide), A1221 (1 mg/kg), or estradiol benzoate (50 μg/kg). Developmental parameters, estrous cyclicity (females), and timing of reproductive senescence were monitored in the offspring through 9 months of age. Expression of 48 genes was measured in 3 hypothalamic nuclei: the anteroventral periventricular nucleus (AVPV), arcuate nucleus (ARC), and median eminence (females only) by real-time RT-PCR. Serum LH, testosterone, and estradiol were assayed in the same animals. In males, A1221 had no effects; however, prenatal estradiol benzoate increased serum estradiol, gene expression in the AVPV (1 gene), and ARC (2 genes) compared with controls. In females, estrous cycles were longer in the A1221-exposed females throughout the life cycle. Gene expression was not affected in the AVPV, but significant changes were caused by A1221 in the ARC and median eminence as a function of cycling status. Bionetwork analysis demonstrated fundamental differences in physiology and gene expression between cycling and acyclic females independent of treatment. Thus, gestational exposure to biologically relevant levels of estrogenic endocrine-disrupting chemicals has sexually dimorphic effects, with an altered transition to reproductive aging in female rats but relatively little effect in males.

Transgenerational effects of polychlorinated biphenyls: 2. Hypothalamic gene expression in rats

2021 ◽  
Author(s):  
Andrea C Gore ◽  
Lindsay M Thompson ◽  
Mandee Bell ◽  
Jan A Mennigen
Keyword(s):  
Gene Expression ◽  
Polychlorinated Biphenyls ◽  
Expression Profiles ◽  
Endocrine Disrupting Chemicals ◽  
Gene Expression Profiles ◽  
Estradiol Benzoate ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Transgenerational Effects ◽  
Aroclor 1221

Abstract Polychlorinated biphenyls (PCBs) are endocrine-disrupting chemicals (EDCs) with well-established effects on reproduction and behavior in developmentally-exposed (F1) individuals. Because of evidence for transgenerational effects of EDCs on the neuroendocrine control of reproductive physiology, we tested the hypothesis that prenatal PCB exposure leads to unique hypothalamic gene expression profiles in three generations. Pregnant Sprague–Dawley rats were treated on gestational days 16 and 18 with the PCB mixture Aroclor 1221 (A1221), vehicle (3% DMSO in sesame oil), or estradiol benzoate (EB, 50 μg/kg), the latter a positive control for estrogenic effects of A1221. Maternal- and paternal-lineage F2 and F3 generations were bred using untreated partners. The anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC), involved in the hypothalamic control of reproduction, were dissected from F1-F3 females and males, RNA extracted, and gene expression measured in a qPCR array. We detected unique gene expression profiles in each generation, that were sex- and lineage-specific. In the AVPV, treatment significantly changed 10, 25, and 11 transcripts in F1, F2, and F3 generations, whereas 10, 1, and 12 transcripts were changed in these generations in the ARC. In the F1 AVPV and ARC, most affected transcripts were decreased by A1221. In the F2 AVPV, most effects of A1221 were observed in females of the maternal lineage, whereas only Pomc expression changed in the F2 ARC (by EB). The F3 AVPV and ARC were mainly affected by EB. It is notable that results in one generation do not predict results in another, and that lineage was a major determinant in results. Thus, transient prenatal exposure of F1 rats to A1221 or EB can alter hypothalamic gene expression across 3 generations in a sex- and lineage-dependent manner, leading to the conclusion that the legacy of PCBs continues for generations.

scholarly journals Symbiotic Gene Activation is Interrupted by Endocrine Disrupting Chemicals

2001 ◽  
Vol 1 ◽  
pp. 653-655 ◽  
Author(s):  
Jennifer E. Fox ◽  
Matthew E. Burow ◽  
John A. McLachlan
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Estrogen Receptors ◽  
Mammalian Cell Culture ◽  
Endocrine Disrupting Chemicals ◽  
Gene Activation ◽  
Symbiotic Gene ◽  
Endocrine Disrupting ◽  
Plant Chemicals ◽  
By Products

Endocrine disrupting chemicals (EDCs) include organochlorine pesticides, plastics manufacturing by-products, and certain herbicides[1]. These chemicals have been shown to disrupt hormonal signaling in exposed wildlife, lab animals, and mammalian cell culture by binding to estrogen receptors (ER-α and ER-β) and affecting the expression of estrogen responsive genes[2,3]. Additionally, certain plant chemicals, termed phytoestrogens, are also able to bind to estrogen receptors and modulate gene expression, and as such also may be considered EDCs[4]. One example of phytoestrogen action is genistein, a phytochemical produced by soybeans, binding estrogen receptors, and changing expression of estrogen responsive genes which certain studies have linked to a lower incidence of hormonally related cancers in Japanese populations[5]. Why would plants make compounds that are able to act as estrogens in the human body? Obviously, soybeans do not intentionally produce phytoestrogens to prevent breast cancer in Japanese women.

Gestational Exposure to Common Endocrine Disrupting Chemicals and Their Impact on Neurodevelopment and Behavior

2020 ◽  
Vol 82 (1) ◽  
pp. 177-202 ◽  
Author(s):  
Dinushan Nesan ◽  
Deborah M. Kurrasch
Keyword(s):  
Endocrine Disruption ◽  
Polybrominated Diphenyl Ethers ◽  
Animal Studies ◽  
Endocrine Disrupting Chemicals ◽  
Lactational Exposure ◽  
Gestational Exposure ◽  
Early Life Exposure ◽  
Endocrine Disrupting ◽  
Physiological Homeostasis ◽  
Nervous System Function

Endocrine disrupting chemicals are common in our environment and act on hormone systems and signaling pathways to alter physiological homeostasis. Gestational exposure can disrupt developmental programs, permanently altering tissues with impacts lasting into adulthood. The brain is a critical target for developmental endocrine disruption, resulting in altered neuroendocrine control of hormonal signaling, altered neurotransmitter control of nervous system function, and fundamental changes in behaviors such as learning, memory, and social interactions. Human cohort studies reveal correlations between maternal/fetal exposure to endocrine disruptors and incidence of neurodevelopmental disorders. Here, we summarize the major literature findings of endocrine disruption of neurodevelopment and concomitant changes in behavior by four major endocrine disruptor classes:bisphenol A, polychlorinated biphenyls, organophosphates, and polybrominated diphenyl ethers. We specifically review studies of gestational and/or lactational exposure to understand the effects of early life exposure to these compounds and summarize animal studies that help explain human correlative data.

Perinatal exposure to mixtures of endocrine disrupting chemicals reduces female rat follicle reserves and accelerates reproductive aging

2016 ◽  
Vol 61 ◽  
pp. 186-194 ◽  
Author(s):  
Hanna Katarina Lilith Johansson ◽  
Pernille Rosenskjold Jacobsen ◽  
Ulla Hass ◽  
Terje Svingen ◽  
Anne Marie Vinggaard ◽  
...  
Keyword(s):  
Endocrine Disrupting Chemicals ◽  
Perinatal Exposure ◽  
Reproductive Aging ◽  
Female Rat ◽  
Endocrine Disrupting

scholarly journals Endocrine Disrupting Chemicals, Phthalic Acid and Nonylphenol, Activate Pregnane X Receptor-Mediated Transcription

2000 ◽  
Vol 14 (3) ◽  
pp. 421-428 ◽  
Author(s):  
Hisashi Masuyama ◽  
Yuji Hiramatsu ◽  
Mamoru Kunitomi ◽  
Takafumi Kudo ◽  
Paul N. MacDonald
Keyword(s):  
Gene Expression ◽  
Bisphenol A ◽  
Nuclear Receptor ◽  
Phthalic Acid ◽  
Steroid Hormone ◽  
Endocrine Disrupting Chemicals ◽  
Pregnane X Receptor ◽  
Specific Gene ◽  
Hormone Metabolism ◽  
Endocrine Disrupting

Abstract Recently, Pregnane X receptor (PXR), a new member of the nuclear receptor superfamily, was shown to mediate the effects of several steroid hormones, such as progesterone, glucocorticoid, pregnenolone, and xenobiotics on cytochrome P450 3A genes (CYP3A) through the specific DNA sequence for CYP3A, suggesting that PXR may play a role in steroid hormone metabolism. In this paper, we demonstrated that phthalic acid and nonylphenol, endocrine-disrupting chemicals (EDCs), stimulated PXR-mediated transcription at concentrations comparable to those at which they activate estrogen receptor-mediated transcription using a transient reporter gene expression assay in COS-7 cells. However, bisphenol A, another EDC, had no effect on PXR-mediated transcription, although this chemical significantly enhanced ER-mediated transcription. In the yeast two-hybrid protein interaction assay, PXR interacted with two nuclear receptor coactivator proteins, steroid hormone receptor coactivator-1 and receptor interacting protein 140, in the presence of phthalic acid or nonylphenol. Thus, EDC-occupied PXR may regulate its specific gene expression through the receptor-coactivator interaction. In contrast, these EDCs had no effect on the interaction between PXR and suppressor for gal 1, a component of proteasome. Finally, the expression of CYP3A1 mRNA in the liver of rats exposed to phthalic acid or nonylphenol markedly increased compared with that in rats treated with estradiol, bisphenol A, or ethanol as assessed by competitive RT-PCR. These data suggest that EDCs may affect endocrine functions by altering steroid hormone metabolism through PXR.

scholarly journals Environmental epigenetics: a role in endocrine disease?

2012 ◽  
Vol 49 (2) ◽  
pp. R61-R67 ◽  
Author(s):  
Abby F Fleisch ◽  
Robert O Wright ◽  
Andrea A Baccarelli
Keyword(s):  
Gene Expression ◽  
Early Life ◽  
Endocrine Disrupting Chemicals ◽  
Environmental Exposures ◽  
Current Evidence ◽  
Epigenetic Mechanisms ◽  
Endocrine Effects ◽  
Endocrine Disease ◽  
Environmental Epigenetics ◽  
Endocrine Disrupting

Endocrine disrupting chemicals that are structurally similar to steroid or amine hormones have the potential to mimic endocrine endpoints at the receptor level. However, more recently, epigenetic-induced alteration in gene expression has emerged as an alternative way in which environmental compounds may exert endocrine effects. We review concepts related to environmental epigenetics and relevance for endocrinology through three broad examples: 1) effect of early-life nutritional exposures on future obesity and insulin resistance, 2) effect of lifetime environmental exposures such as ionizing radiation on endocrine cancer risk, and 3) potential for compounds previously classified as endocrine disrupting to additionally or alternatively exert effects through epigenetic mechanisms. The field of environmental epigenetics is still nascent, and additional studies are needed to confirm and reinforce data derived from animal models and preliminary human studies. Current evidence suggests that environmental exposures may significantly impact expression of endocrine-related genes and thereby affect clinical endocrine outcomes.

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