The Protective Effect of Testosterone on the Ovarian Reserve During Cyclophosphamide Treatment
Received 17 December 2019
Accepted for publication 27 March 2020
Published 8 April 2020 Volume 2020:13 Pages 2987—2995
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Yong Teng
Masae Yoo,1 Tomohito Tanaka,1,2 Hiromi Konishi,1 Akiko Tanabe,1 Kohei Taniguchi,2 Kazumasa Komura,2 Masami Hayashi,1 Masahide Ohmichi1
1Department of Obstetrics and Gynecology; 2Translational Research Program, Osaka Medical College, Takatsuki, Japan
Correspondence: Tomohito Tanaka
Department of Obstetrics and Gynecology, Osaka Medical College, 2-7, Daigaku-machi, Takatsuki, Osaka 569-8686, Japan
Introduction: Cyclophosphamide, which is widely used to treat malignant disease, causes ovarian follicular atresia, which leads to premature ovarian insufficiency. The present study evaluated the protective effect of testosterone in preventing the decline in the ovarian reserve during cyclophosphamide treatment.
Methods: Using the COV434 human granulosa cell line, the protective effect of testosterone against cyclophosphamide was evaluated by immunocytochemistry, Western blotting and an MTS assay. The follicles in mouse ovaries and serum anti-Mullerian hormone were also assessed to evaluate the effects of testosterone.
Results: Testosterone suppressed the decrease in cell viability and apoptosis caused by cyclophosphamide treatment in vitro. In vivo, the number of atretic follicles in the mouse ovary was significantly lower in the testosterone plus cyclophosphamide group than in the cyclophosphamide alone group (p=0.03). The serum anti-Mullerian hormone was significantly higher in the testosterone plus cyclophosphamide group than in the cyclophosphamide alone group (16.2 [9.7– 22.6]) vs 11.2 [8.9– 12.1], p< 0.01). The rate of cleaved Caspase-3 expression in the testosterone plus cyclophosphamide group was lower than that in the cyclophosphamide alone group (28.4% vs 48.6%, p=0.03).
Conclusion: These findings indicated that testosterone has the potential to prevent ovarian damage induced by cyclophosphamide by protecting granulosa cells from cyclophosphamide-induced apoptosis.
Keywords: cyclophosphamide, follicular atresia, granulosa cells, primary ovarian insufficiency, testosterone
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