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...
Main Authors: | , , , , , |
---|---|
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 |