Ovarian mitochondrial dynamics and cell fate regulation in an androgen-induced rat model of polycystic ovarian syndrome

Loading...
Thumbnail Image
File version

Version of Record (VoR)

Author(s)
Salehi, Reza
Mazier, Hannah L
Nivet, Anne-Laure
Reunov, Arkadiy A
Lima, Patricia
Wang, Qi
Fiocco, Arianna
Isidoro, Ciro
Tsang, Benjamin K
Griffith University Author(s)
Primary Supervisor
Other Supervisors
Editor(s)
Date
2020
Size
File type(s)
Location
Abstract

In this study, we investigated in an androgenized rat model the involvement of autophagy and mitochondrial dynamics in granulosa cells in the pathogenesis of polycystic ovarian syndrome (PCOS) and its modulation by exogenous gonadotropin (eCG). We found 5α-dihydrotestosterone (DHT) treatment reduces ovarian length and weight with predominantly late antral and/or preovulatory stage follicles and no corpora lutea. DHT increased the population of large lysosomes (>50 micron) and macroautophagy, an event associated with granulosa cell apoptosis. Increased granulosa cell Dynamin Related Protein 1 (Drp1) content in the DHT group was accompanied by increased circular and constricted, but reduced rod-shaped, mitochondria. eCG eliminated all atypical follicles and increased the number of late antral and preovulatory follicles with less granulosa cell apoptosis. eCG-treated rats had a higher proportion of connected mitochondria, and in combination with DHT had a lower proportion of circular and constricted mitochondria than rats treated with DHT alone, suggesting that eCG induces mitochondrial fusion and attenuates fission in granulosa cells. In summary, we observed that DHT-induced up-regulation of Drp1 is associated with excessive mitochondrial fission, macroautophagy and apoptosis in granulosa cells at the antral stage of development in an androgenized rat model for PCOS, a response partially attenuated by exogenous gonadotropin.

Journal Title

Scientific Reports

Conference Title
Book Title
Edition
Volume

10

Issue
Thesis Type
Degree Program
School
Publisher link
Patent number
Funder(s)
Grant identifier(s)
Rights Statement
Rights Statement

© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Item Access Status
Note
Access the data
Related item(s)
Subject

Obstetrics and gynaecology

Endocrinology

Biochemistry and cell biology

Science & Technology

Multidisciplinary Sciences

Science & Technology - Other Topics

FOLLICULAR DEVELOPMENT

POTENTIAL INVOLVEMENT

Persistent link to this record
Citation

Salehi, R; Mazier, HL; Nivet, A-L; Reunov, AA; Lima, P; Wang, Q; Fiocco, A; Isidoro, C; Tsang, BK, Ovarian mitochondrial dynamics and cell fate regulation in an androgen-induced rat model of polycystic ovarian syndrome, Scientific Reports, 2020, 10, pp. 1021

Collections