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Open AccessArticle

The Ovarian Transcriptome of Reproductively Aged Multiparous Mice: Candidate Genes for Ovarian Cancer Protection

1
Laboratorio de Genómica Aplicada, Departamento de Oncología Básico-Clínica, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile
2
Programa de Virología, ICBM, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile
3
Center for Information Technology, National Institutes of Health, Bethesda, MD 20892, USA
*
Author to whom correspondence should be addressed.
This article is dedicated to the memory of Dr. David J. Munroe.
Biomolecules 2020, 10(1), 113; https://doi.org/10.3390/biom10010113
Received: 22 October 2019 / Revised: 27 December 2019 / Accepted: 30 December 2019 / Published: 9 January 2020
In middle-aged women, the decline of ovarian follicle reserve below a critical threshold marks menopause, leading to hormonal, inflammatory, and metabolic changes linked to disease. The highest incidence and mortality of sporadic ovarian cancer (OC) occur at post-menopause, while OC risk is reduced by full-term pregnancies during former fertile life. Herein, we investigate how parity history modulates the ovarian transcriptome related to such declining follicle pool and systemic inflammation in reproductively-aged mice. Female C57BL/6 mice were housed under multiparous and virgin (nulliparous) breeding regimens from adulthood until estropause. The ovaries were then subjected to follicle count and transcriptional profiling, while a cytokine panel was determined in the sera. As expected, the follicle number was markedly decreased just by aging. Importantly, a significantly higher count of primordial and total follicles was observed in aged multiparous relative to aged virgin ovaries. Consistently, among the 65 genes of higher expression in aged multiparous ovaries, 27 showed a follicle count-like pattern, 21 had traceable evidence of roles in follicular/oocyte homeostasis, and 7 were transforming-growth factor beta (TGF-β)/bone morphogenetic protein (BMP) superfamily members. The remaining genes were enriched in cell chemotaxis and innate-immunity, and resembled the profiles of circulating CXCL1, CXCL2, CXCL5, CSF3, and CCL3, chemokines detected at higher levels in aged multiparous mice. We conclude that multiparity during reproductive life promotes the retention of follicle remnants while improving local (ovarian) and systemic immune-innate surveillance in aged female mice. These findings could underlie the mechanisms by which pregnancy promotes the long-term reduced OC risk observed at post-menopause. View Full-Text
Keywords: age; parity; ovary; transcriptome; follicle; inflammation; mouse model age; parity; ovary; transcriptome; follicle; inflammation; mouse model
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Urzúa, U.; Chacón, C.; Norambuena, M.; Lizama, L.; Sarmiento, S.; Asaki, E.; Powell, J.I.; Ampuero, S. The Ovarian Transcriptome of Reproductively Aged Multiparous Mice: Candidate Genes for Ovarian Cancer Protection. Biomolecules 2020, 10, 113.

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