Protective effect of a mechanistic target of rapamycin inhibitor on an            in vivo model ofcisplatin-induced ovarian          gonadotoxicity

Yuji Tanaka; Fuminori Kimura; Luyi Zheng; Shoji Kaku; Akie Takebayashi; Kyoko Kasahara; Shunichiro Tsuji; Takashi Murakami

doi:10.1538/expanim.18-0042

Original

Protective effect of a mechanistic target of rapamycin inhibitor on an in vivo model ofcisplatin-induced ovarian gonadotoxicity

Yuji Tanaka, Fuminori Kimura, Luyi Zheng, Shoji Kaku, Akie Takebayashi, Kyoko Kasahara, Shunichiro Tsuji, Takashi Murakami

Author information

Yuji Tanaka
Department of Obstetrics and Gynecology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan
Fuminori Kimura
Department of Obstetrics and Gynecology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan
Luyi Zheng
Department of Obstetrics and Gynecology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan
Shoji Kaku
Department of Obstetrics and Gynecology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan
Akie Takebayashi
Department of Obstetrics and Gynecology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan
Kyoko Kasahara
Department of Obstetrics and Gynecology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan
Shunichiro Tsuji
Department of Obstetrics and Gynecology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan
Takashi Murakami
Department of Obstetrics and Gynecology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan

Keywords: chemotherapeutic agent-induced gonadotoxicity, cisplatin, fertility preservation, mechanistic target of rapamycin inhibitor, ovarian protection

JOURNAL FREE ACCESS

2018 Volume 67 Issue 4 Pages 493-500

DOI https://doi.org/10.1538/expanim.18-0042

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Abstract

This study aimed to evaluate the protective effect of everolimus, a mechanistic target of rapamycin (mTOR) inhibitor, on cisplatin chemotherapy-induced ovarian toxicity. Eighty sexually mature, virgin, female, 7-week-old C57BL/6J mice were divided into four groups: control, cisplatin (Cis), everolimus (mTORi), and everolimus plus cisplatin (mTORi+Cis). Mice in the Cis and mTORi+Cis groups were intraperitoneally injected with 2 mg/kg of cisplatin for 15 d. Mice in the mTORi and mTORi+Cis groups were orally administered 2.5 mg/kg of everolimus for 29 d, from one week before the first cisplatin injection to one week after the last cisplatin injection. Histological examinations were performed 24 h after the last everolimus administration. The primordial, primary, and antral follicles were significantly depleted in the Cis group compared with that in the control group, confirming the gonadotoxicity of cisplatin. The number of primordial, secondary, and antral follicles was significantly higher in the mTORi+Cis group than in the Cis group, thereby displaying the effect of mTORi-treatment on ovarian protection. Primordial, secondary, and antral follicle counts were similar in the mTORi+Cis and the control groups. The results of this study indicate a protective effect of an mTOR inhibitor against cisplatin chemotherapy-induced gonadotoxicity in the ovarian reserve in an in vivo mouse model.

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