Disruption of global hypothalamic microRNA (miR) profiles and associated behavioral changes in California mice (Peromyscus californicus) developmentally exposed to endocrine disrupting chemicals

Kaur, Sarabjit; Kinkade, Jessica A.; Green, Madison T.; Martin, Rachel E.; Willemse, Tess E.; Bivens, Nathan J.; Schenk, A. Katrin; Helferich, William G.; Trainor, Brian C.; Fass, Joseph; Settles, Matthew L.; Mao, Jiude; Rosenfeld, Cheryl S.

doi:10.1016/j.yhbeh.2020.104890

Cited by 20 publications

(17 citation statements)

References 81 publications

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“…This result is also comparable to our previous two-hit work in which rats were exposed to PCBs during perinatal development, as juveniles, or both [ 21 , 35 ], and wherein single hits at either age did not predict effects of their combination. Our findings are also consistent with the numerous studies suggesting that mate preference is impaired by developmental EDC exposures [ 6 , 99 , 106 , 107 ]. Collectively, we believe that this body of work is important because the vulnerability of mate preference and sexual selection more broadly to EDCs can have consequences on the reproduction and fitness of a species [ 108 ].…”

Section: Discussionsupporting

confidence: 93%

“…More specifically, in the light:dark box, which is a test of anxiety-like behaviors, NeuroMix females spent less time in the light box, and while they were not significantly different from vehicle females in time freezing, the NeuroMix females had fewer freezing episodes. These results of altered anxiety-like behaviors are consistent with other behavioral work on developmental EDCs [ 17 , 20 , 21 , 98 , 99 ]. In a test of sociability, in which a rat is given a choice between a same-sex conspecific or an empty cage, NeuroMix females showed decreased sociability and increased locomotor activity.…”

Section: Discussionsupporting

confidence: 91%

“…We did not find any effects of treatment in the social novelty test. Other studies on EDCs have also revealed deficits in aspects of social behaviors ([ 99 , 100 ]; reviewed in [ 1 ]).…”

Section: Discussionmentioning

confidence: 99%

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Prenatal Exposure to an EDC Mixture, NeuroMix: Effects on Brain, Behavior, and Stress Responsiveness in Rats

Gore

Moore

Groom

et al. 2022

Toxics

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Humans and wildlife are exposed to endocrine-disrupting chemicals (EDCs) throughout their lives. Environmental EDCs are implicated in a range of diseases/disorders with developmental origins, including neurodevelopment and behavior. EDCs are most often studied one by one; here, we assessed outcomes induced by a mixture designed to represent the real-world situation of multiple simultaneous exposures. The choice of EDCs, which we refer to as “NeuroMix,” was informed by evidence for neurobiological effects in single-compound studies and included bisphenols, phthalates, vinclozolin, and perfluorinated, polybrominated, and polychlorinated compounds. Pregnant Sprague Dawley rats were fed the NeuroMix or vehicle, and then offspring of both sexes were assessed for effects on postnatal development and behaviors and gene expression in the brain in adulthood. In order to determine whether early-life EDCs predisposed to subsequent vulnerability to postnatal life challenges, a subset of rats were also given a stress challenge in adolescence. Prenatal NeuroMix exposure decreased body weight and delayed puberty in males but not females. In adulthood, NeuroMix caused changes in anxiety-like, social, and mate preference behaviors only in females. Effects of stress were predominantly observed in males. Several interactions of NeuroMix and stress were found, especially for the mate preference behavior and gene expression in the brain. These findings provide novel insights into how two realistic environmental challenges lead to developmental and neurobehavioral deficits, both alone and in combination, in a sex-specific manner.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 91%

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Prenatal Exposure to an EDC Mixture, NeuroMix: Effects on Brain, Behavior, and Stress Responsiveness in Rats

Gore

Moore

Groom

et al. 2022

Toxics

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“…Genome-wide miR expression profiling revealed that maternal exposure to BPA significantly correlated with overexpression of miR-146a in whole placenta (De Felice et al, 2015). In experiments with California mice exposed to BPA, genistein, or the combination of these two EDCs, we found that developmental exposure to one or both compounds upregulated miR-146 in the hypothalamus of males and females (Kaur et al, 2021). In the testes, BPA induced miR-146a-5p that in turn impaired steroidogenesis through negative regulation of Metastatic tumor antigen 3 (MTA3) signaling (Gao et al, 2018).…”

Section: Micrornas and Long Non-coding Rnasmentioning

confidence: 82%

“…BPA exposure has been linked to changes in miR expression patterns in whole placenta and TB cell lines (Avissar-Whiting et al, 2010;De Felice et al, 2015;Gao et al, 2018;Kaur et al, 2021). BPA treatment of human immortalized cytoTB cell lines and subsequent microarray analysis showed that several miRs had altered expression following this treatment, in particular miR-146a expression was strongly upregulated by BPA (Avissar-Whiting et al, 2010).…”

Section: Micrornas and Long Non-coding Rnasmentioning

confidence: 99%

Transcriptomics and Other Omics Approaches to Investigate Effects of Xenobiotics on the Placenta

Rosenfeld

2021

Front. Cell Dev. Biol.

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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 possesses a tightly regulated endocrine system that is, of itself, vulnerable to pharmaceutical agents, endocrine disrupting chemicals (EDCs), and other environmental toxicants. To determine whether extrinsic factors affect placental function, transcriptomics and other omics approaches have become more widely used. In casting a wide net with such approaches, they have provided mechanistic insights into placental physiological and pathological responses and how placental responses may impact the fetus, especially the developing brain through the placenta-brain axis. This review will discuss how such omics technologies have been utilized to understand effects of EDCs, including the widely prevalent plasticizers bisphenol A (BPA), bisphenol S (BPS), and phthalates, other environmental toxicants, pharmaceutical agents, maternal smoking, and air pollution on placental gene expression, DNA methylation, and metabolomic profiles. It is also increasingly becoming clear that miRNA (miR) are important epigenetic regulators of placental function. Thus, the evidence to date that xenobiotics affect placental miR expression patterns will also be explored. Such omics approaches with mouse and human placenta will assuredly provide key biomarkers that may be used as barometers of exposure and can be targeted by early mitigation approaches to prevent later diseases, in particular neurobehavioral disorders, originating due to placental dysfunction.

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Micromanaging the neuroendocrine system – A review on miR‐7 and the other physiologically relevant miRNAs in the hypothalamic–pituitary axis

Zacharjasz,

Sztachera,

Smuszkiewicz

et al. 2024

FEBS Letters

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The hypothalamic–pituitary axis is central to the functioning of the neuroendocrine system and essential for regulating physiological and behavioral homeostasis and coordinating fundamental body functions. The expanding line of evidence shows the indispensable role of the microRNA pathway in regulating the gene expression profile in the developing and adult hypothalamus and pituitary gland. Experiments provoking a depletion of miRNA maturation in the context of the hypothalamic–pituitary axis brought into focus a prominent involvement of miRNAs in neuroendocrine functions. There are also a few individual miRNAs and miRNA families that have been studied in depth revealing their crucial role in mediating the regulation of fundamental processes such as temporal precision of puberty timing, hormone production, fertility and reproduction capacity, and energy balance. Among these miRNAs, miR‐7 was shown to be hypothalamus‐enriched and the top one highly expressed in the pituitary gland, where it has a profound impact on gene expression regulation. Here, we review miRNA profiles, knockout phenotypes, and miRNA interaction (targets) in the hypothalamic–pituitary axis that advance our understanding of the roles of miRNAs in mammalian neurosecretion and related physiology.

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Disruption of global hypothalamic microRNA (miR) profiles and associated behavioral changes in California mice (Peromyscus californicus) developmentally exposed to endocrine disrupting chemicals

Cited by 20 publications

References 81 publications

Prenatal Exposure to an EDC Mixture, NeuroMix: Effects on Brain, Behavior, and Stress Responsiveness in Rats

Prenatal Exposure to an EDC Mixture, NeuroMix: Effects on Brain, Behavior, and Stress Responsiveness in Rats

Transcriptomics and Other Omics Approaches to Investigate Effects of Xenobiotics on the Placenta

Micromanaging the neuroendocrine system – A review on miR‐7 and the other physiologically relevant miRNAs in the hypothalamic–pituitary axis

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