High Housing Density-Induced Chronic Stress Diminishes Ovarian Reserve via Granulosa Cell Apoptosis by Angiotensin II Overexpression in Mice

Repeated and prolonged stress causes hypothalamic-pituitary-adrenal (HPA) dysregulation. Excessive hypothalamic-pituitary-adrenal axis activity has been linked to inadequate activation of the hypothalamus-pituitary-ovarian axis, which controls the growth and development of ovarian follicles and oocy...

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Main Authors: Jihyun Kim, Sooseong You
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/15/8614
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author Jihyun Kim
Sooseong You
author_facet Jihyun Kim
Sooseong You
author_sort Jihyun Kim
collection DOAJ
description Repeated and prolonged stress causes hypothalamic-pituitary-adrenal (HPA) dysregulation. Excessive hypothalamic-pituitary-adrenal axis activity has been linked to inadequate activation of the hypothalamus-pituitary-ovarian axis, which controls the growth and development of ovarian follicles and oocytes. Therefore, we assessed the ovarian reserve under high-housing-density-induced prolonged stress, and investigated the mechanisms underlying diminished ovarian reserve in this study. Eight-week-old female C57BL/6 mice were housed for 10 weeks under different housing densities. We then assessed hormone levels, performed histology and immunohistochemistry analyses of ovarian follicles, evaluated ovarian mRNA expression, and measured angiotensin II-mediated apoptosis in vitro. More densely housed mice presented increased corticosterone levels and decreased follicle-stimulating and luteinizing hormone levels. Moreover, mice exposed to prolonged ordinary stress showed a reduced level of serum anti-Müllerian hormone and an increased number of atretic ovarian follicles. Stressed mice showed increased levels of angiotensinogen and angiotensin II in the ovaries and serum. Furthermore, our in vitro study confirmed that high-housing-density-related stress induced granulosa cell apoptosis, resulting in diminished ovarian reserves. Collectively, our findings highlight the importance of women managing everyday stress to maintain their reproductive health.
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spelling doaj.art-74498ea6f7df4b7c9574021f49a14cc22023-11-30T22:29:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012315861410.3390/ijms23158614High Housing Density-Induced Chronic Stress Diminishes Ovarian Reserve via Granulosa Cell Apoptosis by Angiotensin II Overexpression in MiceJihyun Kim0Sooseong You1KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, KoreaKM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, KoreaRepeated and prolonged stress causes hypothalamic-pituitary-adrenal (HPA) dysregulation. Excessive hypothalamic-pituitary-adrenal axis activity has been linked to inadequate activation of the hypothalamus-pituitary-ovarian axis, which controls the growth and development of ovarian follicles and oocytes. Therefore, we assessed the ovarian reserve under high-housing-density-induced prolonged stress, and investigated the mechanisms underlying diminished ovarian reserve in this study. Eight-week-old female C57BL/6 mice were housed for 10 weeks under different housing densities. We then assessed hormone levels, performed histology and immunohistochemistry analyses of ovarian follicles, evaluated ovarian mRNA expression, and measured angiotensin II-mediated apoptosis in vitro. More densely housed mice presented increased corticosterone levels and decreased follicle-stimulating and luteinizing hormone levels. Moreover, mice exposed to prolonged ordinary stress showed a reduced level of serum anti-Müllerian hormone and an increased number of atretic ovarian follicles. Stressed mice showed increased levels of angiotensinogen and angiotensin II in the ovaries and serum. Furthermore, our in vitro study confirmed that high-housing-density-related stress induced granulosa cell apoptosis, resulting in diminished ovarian reserves. Collectively, our findings highlight the importance of women managing everyday stress to maintain their reproductive health.https://www.mdpi.com/1422-0067/23/15/8614stresstranscriptomic changesangiotensin IIgranulosa cellapoptosisdiminished ovarian reserve
spellingShingle Jihyun Kim
Sooseong You
High Housing Density-Induced Chronic Stress Diminishes Ovarian Reserve via Granulosa Cell Apoptosis by Angiotensin II Overexpression in Mice
International Journal of Molecular Sciences
stress
transcriptomic changes
angiotensin II
granulosa cell
apoptosis
diminished ovarian reserve
title High Housing Density-Induced Chronic Stress Diminishes Ovarian Reserve via Granulosa Cell Apoptosis by Angiotensin II Overexpression in Mice
title_full High Housing Density-Induced Chronic Stress Diminishes Ovarian Reserve via Granulosa Cell Apoptosis by Angiotensin II Overexpression in Mice
title_fullStr High Housing Density-Induced Chronic Stress Diminishes Ovarian Reserve via Granulosa Cell Apoptosis by Angiotensin II Overexpression in Mice
title_full_unstemmed High Housing Density-Induced Chronic Stress Diminishes Ovarian Reserve via Granulosa Cell Apoptosis by Angiotensin II Overexpression in Mice
title_short High Housing Density-Induced Chronic Stress Diminishes Ovarian Reserve via Granulosa Cell Apoptosis by Angiotensin II Overexpression in Mice
title_sort high housing density induced chronic stress diminishes ovarian reserve via granulosa cell apoptosis by angiotensin ii overexpression in mice
topic stress
transcriptomic changes
angiotensin II
granulosa cell
apoptosis
diminished ovarian reserve
url https://www.mdpi.com/1422-0067/23/15/8614
work_keys_str_mv AT jihyunkim highhousingdensityinducedchronicstressdiminishesovarianreserveviagranulosacellapoptosisbyangiotensiniioverexpressioninmice
AT sooseongyou highhousingdensityinducedchronicstressdiminishesovarianreserveviagranulosacellapoptosisbyangiotensiniioverexpressioninmice