A gonadotropin-releasing hormone agonist for the prevention of docetaxel-induced gonadal damage

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Abstract

This study aimed to evaluate the protective effect of a gonadotropin-releasing hormone (GnRH) agonist against docetaxel-induced gonadotoxicity in a mouse model. Forty mice (female B6, 6–8 weeks old, weighing 16–18 g) were divided randomly into four groups. Groups 1 and 2 were treated with a single intraperitoneal dose of 0.1 mL normal saline; Groups 3 and 4 received 30 mg/kg docetaxel. Groups 2 and 4 were pre-treated with a subcutaneous injection of 0.3 mg leuprolide acetate, 2 weeks before the administration of docetaxel. The ovaries were removed 6 weeks after docetaxel or saline injection. Total follicle number decreased in Group 3 compared to Group 1. There was a significant difference between the Groups 3 and 4 in the total follicle number. Many ovarian follicles were stained for Ki-67 in Groups 1, 2, and 4; however, in Group 3, only a small number were stained and destruction of the ovarian structure was observed. There was no immunohistochemistry staining with γ-H2AX in Groups 1, 2, and 4. However, γ-H2AX staining of the primordial follicles was observed in Group 3. GnRH agonists may protect ovarian follicles from docetaxel-induced ovarian damage considering the total follicle number, follicle proliferation, and double-strand DNA breaks.Impact statement Protection of the ovarian reserve and prevention of infertility are the primary quality of life issues in young cancer patients. In this study, ovarian suppression by gonadotropin-releasing hormone agonists protected ovarian follicles from docetaxel-induced ovarian damage considering the total follicle number, follicle proliferation, and double-strand DNA break. The findings of our study will provide useful information for fertility preservation in women with cancer, undergoing chemotherapy with docetaxel.

Original languageEnglish
Pages (from-to)783-789
Number of pages7
JournalJournal of Obstetrics and Gynaecology
Volume37
Issue number6
DOIs
Publication statusPublished - 2017 Aug 18

Fingerprint

docetaxel
Gonadotropin-Releasing Hormone
Ovarian Follicle
Double-Stranded DNA Breaks
Fertility Preservation
Staining and Labeling
Leuprolide
Subcutaneous Injections
Primary Prevention
Infertility
Ovary
Neoplasms

Keywords

  • Chemotherapy
  • docetaxel
  • gonadotoxicity
  • gonadotropin-releasing hormone agonist
  • H2AX
  • primordial follicle

ASJC Scopus subject areas

  • Obstetrics and Gynaecology

Cite this

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title = "A gonadotropin-releasing hormone agonist for the prevention of docetaxel-induced gonadal damage",
abstract = "This study aimed to evaluate the protective effect of a gonadotropin-releasing hormone (GnRH) agonist against docetaxel-induced gonadotoxicity in a mouse model. Forty mice (female B6, 6–8 weeks old, weighing 16–18 g) were divided randomly into four groups. Groups 1 and 2 were treated with a single intraperitoneal dose of 0.1 mL normal saline; Groups 3 and 4 received 30 mg/kg docetaxel. Groups 2 and 4 were pre-treated with a subcutaneous injection of 0.3 mg leuprolide acetate, 2 weeks before the administration of docetaxel. The ovaries were removed 6 weeks after docetaxel or saline injection. Total follicle number decreased in Group 3 compared to Group 1. There was a significant difference between the Groups 3 and 4 in the total follicle number. Many ovarian follicles were stained for Ki-67 in Groups 1, 2, and 4; however, in Group 3, only a small number were stained and destruction of the ovarian structure was observed. There was no immunohistochemistry staining with γ-H2AX in Groups 1, 2, and 4. However, γ-H2AX staining of the primordial follicles was observed in Group 3. GnRH agonists may protect ovarian follicles from docetaxel-induced ovarian damage considering the total follicle number, follicle proliferation, and double-strand DNA breaks.Impact statement Protection of the ovarian reserve and prevention of infertility are the primary quality of life issues in young cancer patients. In this study, ovarian suppression by gonadotropin-releasing hormone agonists protected ovarian follicles from docetaxel-induced ovarian damage considering the total follicle number, follicle proliferation, and double-strand DNA break. The findings of our study will provide useful information for fertility preservation in women with cancer, undergoing chemotherapy with docetaxel.",
keywords = "Chemotherapy, docetaxel, gonadotoxicity, gonadotropin-releasing hormone agonist, H2AX, primordial follicle",
author = "Ilhae Park and Sanghoon Lee and Ryu, {Ki Jin} and Min, {Kyung Jin} and Jin-Hwa Hong and Song, {Jae Yun} and Lee, {Jae Kwan} and Lee, {Nak Woo}",
year = "2017",
month = "8",
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doi = "10.1080/01443615.2017.1306839",
language = "English",
volume = "37",
pages = "783--789",
journal = "Journal of Obstetrics and Gynaecology",
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T1 - A gonadotropin-releasing hormone agonist for the prevention of docetaxel-induced gonadal damage

AU - Park, Ilhae

AU - Lee, Sanghoon

AU - Ryu, Ki Jin

AU - Min, Kyung Jin

AU - Hong, Jin-Hwa

AU - Song, Jae Yun

AU - Lee, Jae Kwan

AU - Lee, Nak Woo

PY - 2017/8/18

Y1 - 2017/8/18

N2 - This study aimed to evaluate the protective effect of a gonadotropin-releasing hormone (GnRH) agonist against docetaxel-induced gonadotoxicity in a mouse model. Forty mice (female B6, 6–8 weeks old, weighing 16–18 g) were divided randomly into four groups. Groups 1 and 2 were treated with a single intraperitoneal dose of 0.1 mL normal saline; Groups 3 and 4 received 30 mg/kg docetaxel. Groups 2 and 4 were pre-treated with a subcutaneous injection of 0.3 mg leuprolide acetate, 2 weeks before the administration of docetaxel. The ovaries were removed 6 weeks after docetaxel or saline injection. Total follicle number decreased in Group 3 compared to Group 1. There was a significant difference between the Groups 3 and 4 in the total follicle number. Many ovarian follicles were stained for Ki-67 in Groups 1, 2, and 4; however, in Group 3, only a small number were stained and destruction of the ovarian structure was observed. There was no immunohistochemistry staining with γ-H2AX in Groups 1, 2, and 4. However, γ-H2AX staining of the primordial follicles was observed in Group 3. GnRH agonists may protect ovarian follicles from docetaxel-induced ovarian damage considering the total follicle number, follicle proliferation, and double-strand DNA breaks.Impact statement Protection of the ovarian reserve and prevention of infertility are the primary quality of life issues in young cancer patients. In this study, ovarian suppression by gonadotropin-releasing hormone agonists protected ovarian follicles from docetaxel-induced ovarian damage considering the total follicle number, follicle proliferation, and double-strand DNA break. The findings of our study will provide useful information for fertility preservation in women with cancer, undergoing chemotherapy with docetaxel.

AB - This study aimed to evaluate the protective effect of a gonadotropin-releasing hormone (GnRH) agonist against docetaxel-induced gonadotoxicity in a mouse model. Forty mice (female B6, 6–8 weeks old, weighing 16–18 g) were divided randomly into four groups. Groups 1 and 2 were treated with a single intraperitoneal dose of 0.1 mL normal saline; Groups 3 and 4 received 30 mg/kg docetaxel. Groups 2 and 4 were pre-treated with a subcutaneous injection of 0.3 mg leuprolide acetate, 2 weeks before the administration of docetaxel. The ovaries were removed 6 weeks after docetaxel or saline injection. Total follicle number decreased in Group 3 compared to Group 1. There was a significant difference between the Groups 3 and 4 in the total follicle number. Many ovarian follicles were stained for Ki-67 in Groups 1, 2, and 4; however, in Group 3, only a small number were stained and destruction of the ovarian structure was observed. There was no immunohistochemistry staining with γ-H2AX in Groups 1, 2, and 4. However, γ-H2AX staining of the primordial follicles was observed in Group 3. GnRH agonists may protect ovarian follicles from docetaxel-induced ovarian damage considering the total follicle number, follicle proliferation, and double-strand DNA breaks.Impact statement Protection of the ovarian reserve and prevention of infertility are the primary quality of life issues in young cancer patients. In this study, ovarian suppression by gonadotropin-releasing hormone agonists protected ovarian follicles from docetaxel-induced ovarian damage considering the total follicle number, follicle proliferation, and double-strand DNA break. The findings of our study will provide useful information for fertility preservation in women with cancer, undergoing chemotherapy with docetaxel.

KW - Chemotherapy

KW - docetaxel

KW - gonadotoxicity

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KW - H2AX

KW - primordial follicle

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