Mechanism of action of IHH in ameliorating thin endometrium

A thin endometrium can lead to low clinical pregnancy rates, low live birth rates, high spontaneous abortion rates, and low birth weight. However, current methods of treating thin endometria do not achieve ideal results. This study explored the effect of Indian Hedgehog (IHH) on thin endometrium and...

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Main Authors: Lan LUO, Man LUO, Donghong NING, Xi CHEN, Qiuman ZHENG, Qin CAO
Format: Article
Language:English
Published: The Society for Reproduction and Development 2025-04-01
Series:The Journal of Reproduction and Development
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Online Access:https://www.jstage.jst.go.jp/article/jrd/71/3/71_2024-096/_pdf/-char/en
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author Lan LUO
Man LUO
Donghong NING
Xi CHEN
Qiuman ZHENG
Qin CAO
author_facet Lan LUO
Man LUO
Donghong NING
Xi CHEN
Qiuman ZHENG
Qin CAO
author_sort Lan LUO
collection DOAJ
description A thin endometrium can lead to low clinical pregnancy rates, low live birth rates, high spontaneous abortion rates, and low birth weight. However, current methods of treating thin endometria do not achieve ideal results. This study explored the effect of Indian Hedgehog (IHH) on thin endometrium and its mechanism of action. A thin endometrial rat model was established by infusion of 95% ethanol. IHH was overexpressed in model rats using adeno-associated viruses. The endometrial thickness and number of glands and vessels were determined using H&E staining. Endometrial fibrosis was detected using Masson’s trichrome staining. Immunohistochemistry was performed to detect α-SMA, MUC-1, and CK19. After modeling, the rats were mated, and the number of gestational sacs was counted for fertility assessment. Western blotting was used to detect the angiogenesis markers vWF, PCNA, and vim and Hedgehog signaling-related proteins SMO, GLI1, and GLI3. IHH overexpression reduced ethanol-induced edema and bruising, repaired the appearance of damaged tissue, increased endometrial thickness, promoted glandular and vascular regeneration, and alleviated endometrial fibrosis. IHH overexpression inhibited the expression of fibroblast marker α-SMA while promoting the expression of vWF, PCNA, vim, CK19, and MUC-1. It also increased the number of gestational sacs and promoted the expression of SMO, GLI1, and GLI3. In conclusion, IHH ameliorates ethanol-induced thin endometrium and improves fertility by activating the Hedgehog signaling pathway.
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spelling doaj-art-a03089ab473847e58a72dc0a85fa3aef2025-08-20T03:24:37ZengThe Society for Reproduction and DevelopmentThe Journal of Reproduction and Development0916-88181348-44002025-04-0171316116710.1262/jrd.2024-096jrdMechanism of action of IHH in ameliorating thin endometriumLan LUO0Man LUO1Donghong NING2Xi CHEN3Qiuman ZHENG4Qin CAO5Department of TCM Gynecology, Hunan Provincial Maternal and Child Health Care Hospital, Hunan 410008, P.R. ChinaDepartment of TCM Gynecology, Hunan Provincial Maternal and Child Health Care Hospital, Hunan 410008, P.R. ChinaDepartment of TCM Gynecology, Hunan Provincial Maternal and Child Health Care Hospital, Hunan 410008, P.R. ChinaDepartment of TCM Gynecology, Hunan Provincial Maternal and Child Health Care Hospital, Hunan 410008, P.R. ChinaHunan University of Chinese Medicine, Hunan 410208, P.R. ChinaHunan University of Chinese Medicine, Hunan 410208, P.R. ChinaA thin endometrium can lead to low clinical pregnancy rates, low live birth rates, high spontaneous abortion rates, and low birth weight. However, current methods of treating thin endometria do not achieve ideal results. This study explored the effect of Indian Hedgehog (IHH) on thin endometrium and its mechanism of action. A thin endometrial rat model was established by infusion of 95% ethanol. IHH was overexpressed in model rats using adeno-associated viruses. The endometrial thickness and number of glands and vessels were determined using H&E staining. Endometrial fibrosis was detected using Masson’s trichrome staining. Immunohistochemistry was performed to detect α-SMA, MUC-1, and CK19. After modeling, the rats were mated, and the number of gestational sacs was counted for fertility assessment. Western blotting was used to detect the angiogenesis markers vWF, PCNA, and vim and Hedgehog signaling-related proteins SMO, GLI1, and GLI3. IHH overexpression reduced ethanol-induced edema and bruising, repaired the appearance of damaged tissue, increased endometrial thickness, promoted glandular and vascular regeneration, and alleviated endometrial fibrosis. IHH overexpression inhibited the expression of fibroblast marker α-SMA while promoting the expression of vWF, PCNA, vim, CK19, and MUC-1. It also increased the number of gestational sacs and promoted the expression of SMO, GLI1, and GLI3. In conclusion, IHH ameliorates ethanol-induced thin endometrium and improves fertility by activating the Hedgehog signaling pathway.https://www.jstage.jst.go.jp/article/jrd/71/3/71_2024-096/_pdf/-char/enfertilityhedgehog signaling pathwayindian hedgehog (ihh)thin endometrium
spellingShingle Lan LUO
Man LUO
Donghong NING
Xi CHEN
Qiuman ZHENG
Qin CAO
Mechanism of action of IHH in ameliorating thin endometrium
The Journal of Reproduction and Development
fertility
hedgehog signaling pathway
indian hedgehog (ihh)
thin endometrium
title Mechanism of action of IHH in ameliorating thin endometrium
title_full Mechanism of action of IHH in ameliorating thin endometrium
title_fullStr Mechanism of action of IHH in ameliorating thin endometrium
title_full_unstemmed Mechanism of action of IHH in ameliorating thin endometrium
title_short Mechanism of action of IHH in ameliorating thin endometrium
title_sort mechanism of action of ihh in ameliorating thin endometrium
topic fertility
hedgehog signaling pathway
indian hedgehog (ihh)
thin endometrium
url https://www.jstage.jst.go.jp/article/jrd/71/3/71_2024-096/_pdf/-char/en
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AT donghongning mechanismofactionofihhinamelioratingthinendometrium
AT xichen mechanismofactionofihhinamelioratingthinendometrium
AT qiumanzheng mechanismofactionofihhinamelioratingthinendometrium
AT qincao mechanismofactionofihhinamelioratingthinendometrium