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The effects of early life adversity on growth, maturation, and steroid hormones in male and female rats.

ABSTRACT: Early life adversity is a risk factor for psychiatric disorders, yet the mechanisms by which adversity increases this risk are still being delineated. Here, we used a limited bedding and nesting (LBN) manipulation in rats that models a low resource environment to examine effects on growth, developmental milestones, and endocrine endpoints. In LBN, dams and pups, from pups' postnatal days 2-9, are exposed to an environment where dams lack proper materials to build a nest. This manipulation is compared to control housing conditions, where rat dams have access to ample nesting materials and enrichment throughout pups' development. We found that the LBN condition altered maternal care, increasing pup-directed behaviors while reducing self-care. This, perhaps compensatory, increase in nursing and attention to pups did not mitigate against changes in metabolism, as LBN reduced weight gain in both sexes and this effect persisted into adulthood. Although adult stress hormone levels in both sexes and vaginal opening and estrous cycle length in females were not disrupted, there was other evidence of endocrine dysregulation. Compared to controls, LBN rats of both sexes had shortened anogenital distances, indicating reduced androgen exposure. LBN males also had higher plasma estradiol levels in adulthood. This combination of results suggests that LBN causes a demasculinizing effect in males that could contribute to lasting changes in the brain and behavior. Importantly, alterations in metabolic and endocrine systems due to early life adversity could be one mechanism by which stress early in life increases risk for later disease.

SUBMITTER: Eck SR

PROVIDER: S-EPMC8027906 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Cerebellar Interpositus Nucleus Transcriptome Following Early-Life Limited Bedding Stress in P70 Male and Female Rats

Project description:Purpose: This particular experiment is part of a broader study on the effects of early-life stress on the cerebellar endocannabinoid system. Early-life stress is a major developmental risk factor. Though studies are now considering the endogenous cannabinoid system, which is highly intertwied with the stress-response, as a moderator of these effects, studies have been largely focused on cerebral effects. Cerebellum is vulnerable to stress during early development and is dense with cannabinoid receptors, making it an important target for stress effects. Moreover, relatively little is known about sex-specific effects in cerebellum. Methods: Limited bedding, a naturalistic rodent model of early-life stress, was performed at postnatal days 2-9. Following, rats were reared normally and adult (postnatal day 70) cerebellar interpositus nucleus mRNA was assessed. Results: Transcriptomics for cerebellar interpositus nucleus revealed substantial sex effects, with minimal effects of stress. Specifically, expression of 25% of the genes evaluated significantly differed by sex alone. Interestingly, in the non-stressed groups, there were significant sex differences in Cnr1, cannabinoid receptor 1. Conclusion: We show robust sex-specific transcriptomics effects in cerebellar interpositus, perhaps suggesting a role for this system in sexual differentiation of the brain. Other regions of cerebellum should be evaluated.

2020-04-29 | GSE139953 | GEO

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