Amany I. Ahmed, Mohamed F. Dowidar, Asmaa F. Negm, Hussein Abdellatif, Asma Alanazi, Mohammed Alassiri, Walaa Samy, Dina Mohamed Mekawy, Eman M. A. Abdelghany, Nesma I. El-Naseery, Mohamed A. Ibrahem, Emad Ali Albadawi, Wed Salah, Mamdouh Eldesoqui, Emil Tîrziu, Iulia Maria Bucur, Ahmed Hamed Arisha, Tarek Khamis
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引用次数: 0
摘要
卵巢功能不全是影响妇女的常见生殖疾病之一,但治疗手段有限。间充质干细胞曾被研究用于此类疾病,但间充质干细胞在卵巢再生中的表观遗传调控的确切机制仍未确定。本研究旨在探讨骨髓间充质干细胞(BM-MSCs)lncRNA(Neat-1和Hotair1)和miRNA(mir-21-5p、mir-144-5p和mir-664-5p)在卵巢再生中的作用、和mir-664-5p)在减轻卵巢颗粒细胞凋亡中的作用,以及在环磷酰胺诱导的卵巢功能衰竭大鼠模型中寻找BM-间充质干细胞在改变卵巢和下丘脑IGF-1-kisspeptin系统表达与HPG轴的关系中的作用。将 60 只成熟的 Sprague Dawley 雌性大鼠分为 3 组:对照组、卵巢早衰(POI)组和 POI + BM-间充质干细胞组。POI雌性大鼠模型是用环磷酰胺建立的。结果显示,BM-间充质干细胞及其条件培养基显示了Neat-1、Hotair-1、mir-21-5p、mir-144-5p和mir-664-5p的显著表达水平。此外,BM-间充质干细胞移植到 POI 大鼠体内可改善卵巢和下丘脑 IGF-1 - 吻肽、HPG 轴、卵巢颗粒细胞凋亡、类固醇生成、血管生成、能量平衡和氧化应激。BM-间充质干细胞表达了更高水平的抗凋亡lncRNAs和microRNAs,可缓解卵巢功能不全。
Bone marrow mesenchymal stem cells expressing Neat-1, Hotair-1, miR-21, miR-644, and miR-144 subsided cyclophosphamide-induced ovarian insufficiency by remodeling the IGF-1–kisspeptin system, ovarian apoptosis, and angiogenesis
Ovarian insufficiency is one of the common reproductive disorders affecting women with limited therapeutic aids. Mesenchymal stem cells have been investigated in such disorders before yet, the exact mechanism of MSCs in ovarian regeneration regarding their epigenetic regulation remains elusive. The current study is to investigate the role of the bone marrow-derived mesenchymal stem cells (BM-MSCs) lncRNA (Neat-1 and Hotair1) and miRNA (mir-21-5p, mir-144-5p, and mir-664-5p) in mitigating ovarian granulosa cell apoptosis as well as searching BM-MSCs in altering the expression of ovarian and hypothalamic IGF-1 – kisspeptin system in connection to HPG axis in a cyclophosphamide-induced ovarian failure rat model. Sixty mature female Sprague Dawley rats were divided into 3 equal groups; control group, premature ovarian insufficiency (POI) group, and POI + BM-MSCs. POI female rat model was established with cyclophosphamide. The result revealed that BM-MSCs and their conditioned media displayed a significant expression level of Neat-1, Hotair-1, mir-21-5p, mir-144-5p, and mir-664-5p. Moreover, BM-MSCs transplantation in POI rats improves; the ovarian and hypothalamic IGF-1 – kisspeptin, HPG axis, ovarian granulosa cell apoptosis, steroidogenesis, angiogenesis, energy balance, and oxidative stress. BM-MSCs expressed higher levels of antiapoptotic lncRNAs and microRNAs that mitigate ovarian insufficiency.
期刊介绍:
Journal of Ovarian Research is an open access, peer reviewed, online journal that aims to provide a forum for high-quality basic and clinical research on ovarian function, abnormalities, and cancer. The journal focuses on research that provides new insights into ovarian functions as well as prevention and treatment of diseases afflicting the organ.
Topical areas include, but are not restricted to:
Ovary development, hormone secretion and regulation
Follicle growth and ovulation
Infertility and Polycystic ovarian syndrome
Regulation of pituitary and other biological functions by ovarian hormones
Ovarian cancer, its prevention, diagnosis and treatment
Drug development and screening
Role of stem cells in ovary development and function.