The effect of growth hormone on ovarian function recovery in a mouse model of ovarian insufficiency

ObjectivesTo evaluate the effects and mechanisms of action of growth hormone (GH) in the recovery of ovarian function in ovarian insufficiency induced by cyclophosphamide (CP) in a mouse model.Materials and methodsAfter inducing ovarian insufficiency by administering 400 mg/kg of CP intraperitoneall...

Full description

Bibliographic Details
Main Authors: Su Mi Kim, Jung Young Yoo, Yeon Hee Hong, Jaewang Lee, Ji Hyang Kim, Jung Ryeol Lee
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-10-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2023.1184977/full
_version_ 1797667785164193792
author Su Mi Kim
Su Mi Kim
Jung Young Yoo
Jung Young Yoo
Yeon Hee Hong
Yeon Hee Hong
Jaewang Lee
Ji Hyang Kim
Jung Ryeol Lee
Jung Ryeol Lee
author_facet Su Mi Kim
Su Mi Kim
Jung Young Yoo
Jung Young Yoo
Yeon Hee Hong
Yeon Hee Hong
Jaewang Lee
Ji Hyang Kim
Jung Ryeol Lee
Jung Ryeol Lee
author_sort Su Mi Kim
collection DOAJ
description ObjectivesTo evaluate the effects and mechanisms of action of growth hormone (GH) in the recovery of ovarian function in ovarian insufficiency induced by cyclophosphamide (CP) in a mouse model.Materials and methodsAfter inducing ovarian insufficiency by administering 400 mg/kg of CP intraperitoneally to 6-week-old ICR mice, the mice were divided into four groups (control, CP, 1 mg/kg GH, and 2 mg/kg GH) with 10 mice in each group. GH was administered a week later for 7 days. Five mice from each group were sacrificed the next day, and their ovaries were collected for histological examination. The remaining mice were superovulated for in vitro fertilization (IVF). The terminal deoxynucleotidyl transferase dUTP-nick end labeling assay was performed to detect apoptosis. Masson’s trichrome staining was used to analyze the degree of fibrosis. To quantify angiogenesis, CD31 immunohistochemistry was performed. Angiogenesis-related gene expression profiles were assessed using quantitative reverse transcription polymerase chain reaction.ResultsCP induced the loss of non-growing (primordial and primary) follicles while GH significantly protected primordial follicles and increased follicular quality. The CP group showed a decrease in fertilization and blastocyst formation rates in IVF. In contrast, the GH treatment group showed dose-dependent enhanced IVF outcomes. Furthermore, GH treatment decreased apoptosis and stromal fibrosis and increased angiogenesis. Many genes involved in angiogenesis, especially Leptin (Lep), platelet endothelial cell adhesion molecule 1 (Pecam-1), and angiogenin (Ang) were up-regulated in the GH treatment groups.ConclusionGH treatment may promote the recovery of ovarian function in ovarian insufficiency induced by the administration of CP via decreasing apoptosis and stromal fibrosis and upregulating Lep, Pecam-1, and Ang genes.
first_indexed 2024-03-11T20:18:13Z
format Article
id doaj.art-8e4ae0f233774530acfe9272554ace23
institution Directory Open Access Journal
issn 1664-2392
language English
last_indexed 2024-03-11T20:18:13Z
publishDate 2023-10-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Endocrinology
spelling doaj.art-8e4ae0f233774530acfe9272554ace232023-10-03T09:59:16ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-10-011410.3389/fendo.2023.11849771184977The effect of growth hormone on ovarian function recovery in a mouse model of ovarian insufficiencySu Mi Kim0Su Mi Kim1Jung Young Yoo2Jung Young Yoo3Yeon Hee Hong4Yeon Hee Hong5Jaewang Lee6Ji Hyang Kim7Jung Ryeol Lee8Jung Ryeol Lee9Department of Obstetrics and Gynecology, Chungbuk National University Hospital, Cheongju, Republic of KoreaDepartment of Obstetrics and Gynecology, College of Medicine, Seoul National University, Seoul, Republic of KoreaDepartment of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Republic of KoreaDepartment of Biomedical Laboratory Science, Eulji University, Seongnam, Republic of KoreaDepartment of Obstetrics and Gynecology, College of Medicine, Seoul National University, Seoul, Republic of KoreaDepartment of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Republic of KoreaDepartment of Biomedical Laboratory Science, Eulji University, Seongnam, Republic of KoreaDepartment of Obstetrics and Gynecology, Fertility Center of CHA Bundang Medical Center, College of Medicine, CHA University, Seongnam, Republic of KoreaDepartment of Obstetrics and Gynecology, College of Medicine, Seoul National University, Seoul, Republic of KoreaDepartment of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Republic of KoreaObjectivesTo evaluate the effects and mechanisms of action of growth hormone (GH) in the recovery of ovarian function in ovarian insufficiency induced by cyclophosphamide (CP) in a mouse model.Materials and methodsAfter inducing ovarian insufficiency by administering 400 mg/kg of CP intraperitoneally to 6-week-old ICR mice, the mice were divided into four groups (control, CP, 1 mg/kg GH, and 2 mg/kg GH) with 10 mice in each group. GH was administered a week later for 7 days. Five mice from each group were sacrificed the next day, and their ovaries were collected for histological examination. The remaining mice were superovulated for in vitro fertilization (IVF). The terminal deoxynucleotidyl transferase dUTP-nick end labeling assay was performed to detect apoptosis. Masson’s trichrome staining was used to analyze the degree of fibrosis. To quantify angiogenesis, CD31 immunohistochemistry was performed. Angiogenesis-related gene expression profiles were assessed using quantitative reverse transcription polymerase chain reaction.ResultsCP induced the loss of non-growing (primordial and primary) follicles while GH significantly protected primordial follicles and increased follicular quality. The CP group showed a decrease in fertilization and blastocyst formation rates in IVF. In contrast, the GH treatment group showed dose-dependent enhanced IVF outcomes. Furthermore, GH treatment decreased apoptosis and stromal fibrosis and increased angiogenesis. Many genes involved in angiogenesis, especially Leptin (Lep), platelet endothelial cell adhesion molecule 1 (Pecam-1), and angiogenin (Ang) were up-regulated in the GH treatment groups.ConclusionGH treatment may promote the recovery of ovarian function in ovarian insufficiency induced by the administration of CP via decreasing apoptosis and stromal fibrosis and upregulating Lep, Pecam-1, and Ang genes.https://www.frontiersin.org/articles/10.3389/fendo.2023.1184977/fullgrowth hormoneovarian insufficiencycyclophosphamidebreast cancerovarian regenerationfertility preservation
spellingShingle Su Mi Kim
Su Mi Kim
Jung Young Yoo
Jung Young Yoo
Yeon Hee Hong
Yeon Hee Hong
Jaewang Lee
Ji Hyang Kim
Jung Ryeol Lee
Jung Ryeol Lee
The effect of growth hormone on ovarian function recovery in a mouse model of ovarian insufficiency
Frontiers in Endocrinology
growth hormone
ovarian insufficiency
cyclophosphamide
breast cancer
ovarian regeneration
fertility preservation
title The effect of growth hormone on ovarian function recovery in a mouse model of ovarian insufficiency
title_full The effect of growth hormone on ovarian function recovery in a mouse model of ovarian insufficiency
title_fullStr The effect of growth hormone on ovarian function recovery in a mouse model of ovarian insufficiency
title_full_unstemmed The effect of growth hormone on ovarian function recovery in a mouse model of ovarian insufficiency
title_short The effect of growth hormone on ovarian function recovery in a mouse model of ovarian insufficiency
title_sort effect of growth hormone on ovarian function recovery in a mouse model of ovarian insufficiency
topic growth hormone
ovarian insufficiency
cyclophosphamide
breast cancer
ovarian regeneration
fertility preservation
url https://www.frontiersin.org/articles/10.3389/fendo.2023.1184977/full
work_keys_str_mv AT sumikim theeffectofgrowthhormoneonovarianfunctionrecoveryinamousemodelofovarianinsufficiency
AT sumikim theeffectofgrowthhormoneonovarianfunctionrecoveryinamousemodelofovarianinsufficiency
AT jungyoungyoo theeffectofgrowthhormoneonovarianfunctionrecoveryinamousemodelofovarianinsufficiency
AT jungyoungyoo theeffectofgrowthhormoneonovarianfunctionrecoveryinamousemodelofovarianinsufficiency
AT yeonheehong theeffectofgrowthhormoneonovarianfunctionrecoveryinamousemodelofovarianinsufficiency
AT yeonheehong theeffectofgrowthhormoneonovarianfunctionrecoveryinamousemodelofovarianinsufficiency
AT jaewanglee theeffectofgrowthhormoneonovarianfunctionrecoveryinamousemodelofovarianinsufficiency
AT jihyangkim theeffectofgrowthhormoneonovarianfunctionrecoveryinamousemodelofovarianinsufficiency
AT jungryeollee theeffectofgrowthhormoneonovarianfunctionrecoveryinamousemodelofovarianinsufficiency
AT jungryeollee theeffectofgrowthhormoneonovarianfunctionrecoveryinamousemodelofovarianinsufficiency
AT sumikim effectofgrowthhormoneonovarianfunctionrecoveryinamousemodelofovarianinsufficiency
AT sumikim effectofgrowthhormoneonovarianfunctionrecoveryinamousemodelofovarianinsufficiency
AT jungyoungyoo effectofgrowthhormoneonovarianfunctionrecoveryinamousemodelofovarianinsufficiency
AT jungyoungyoo effectofgrowthhormoneonovarianfunctionrecoveryinamousemodelofovarianinsufficiency
AT yeonheehong effectofgrowthhormoneonovarianfunctionrecoveryinamousemodelofovarianinsufficiency
AT yeonheehong effectofgrowthhormoneonovarianfunctionrecoveryinamousemodelofovarianinsufficiency
AT jaewanglee effectofgrowthhormoneonovarianfunctionrecoveryinamousemodelofovarianinsufficiency
AT jihyangkim effectofgrowthhormoneonovarianfunctionrecoveryinamousemodelofovarianinsufficiency
AT jungryeollee effectofgrowthhormoneonovarianfunctionrecoveryinamousemodelofovarianinsufficiency
AT jungryeollee effectofgrowthhormoneonovarianfunctionrecoveryinamousemodelofovarianinsufficiency