Effect of umbilical cord-derived mesenchymal stem cells on the expression of TIMP1, FN and MMP9 in a rabbit model of premature ovarian failure
10.3760/cma.j.cn101441-20200601-00322
- VernacularTitle:脐带间充质干细胞对卵巢早衰模型家兔TIMP1、FN和MMP9表达的影响
- Author:
Juan ZHANG
1
;
Li ZHOU
;
Yao DUAN
;
Xiabei YAN
;
Ping TUO
;
Gang WANG
Author Information
1. 中国人民解放军中部战区总医院生殖医学科，武汉430070
- Publication Type:Journal Article
- Keywords:
Mesenchymal stem cells;
Tissue inhibitor of metalloproteinases;
Fibronectin;
Matrix metalloproteinases;
Premature ovarian failure
- From:
Chinese Journal of Reproduction and Contraception
2021;41(12):1071-1078
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the potential molecular mechanism of umbilical cord-derived mesenchymal stem cells (UCMSCs) to improve ovarian function in premature ovarian failure (POF) rabbits.Methods:Ten rabbits were randomly divided into 2 groups (five rabbits in each), treatment group and model group. A rabbit model of POF was established using an intraperitoneal injection of cyclophosphamide for 2 d (50 mg·kg -1·d -1). After a week, the treatment group received UCMSCs intravenously via a marginal ear vein and model group received equal amounts of sterile water. Ovarian samples were collected on day 28 and ovaries morphology was observed by hematoxylin-eosin staining. Tissue inhibitor of metalloproteinases 1 (TIMP1), fibronectin (FN) and matrix metalloproteinases 9 (MMP9) protein and mRNA expression were detected by Western blotting, PCR, and immunohistochemistry. Results:1) In model group, ovaries of the ovarian tissue displayed as reduced number of primordial follicles, along with increased number of atretic follicles. The granular layer cells of every follicle grade were arranged in disorder. The oocyte nucleus appeared pyknotic and apoptotic changed. Fibrosis was performed in the ovarian stroma. While in treatment group, the number of primordial and primary follicles in the ovarian tissue was large, and there were few atretic follicles. The granule cells of every follicle grade were arranged regularly. 2) Compared with model group, the expressions of TIMP1 protein (0.546±0.021 vs. 0.820±0.085) and FN protein (0.221±0.065 vs. 0.516±0.064) in treatment group were significantly increased (all P<0.001), while the expression of MMP9 protein (0.504±0.049 vs. 0.204±0.066) in treatment group was significantly decreased ( P<0.001). 3) Compared with model group, the expressions of TIMP1 mRNA (0.217±0.024 vs. 0.470±0.039) and FN mRNA (0.039±0.006 vs. 0.125±0.012) in treatment group were significantly increased (all P<0.001), while the expression of MMP9 mRNA (0.009±0.000 vs. 0.002±0.000) in treatment group was significantly decreased ( P<0.001). 4) TIMP1 and FN were mainly expressed in the granule cells and egg cell membranes. TIMP1 was also expressed in ovarian interstitial tissue, and the expression levels were significantly increased in treatment group compared with model group ( P<0.001, P=0.005). MMP9 was mainly expressed in granule cells and ovarian interstitial tissue, and the expression levels were significantly decreased in treatment group compared with model group ( P<0.001). Conclusion:UCMSCs were able to improve ovarian function by regulating the levels of TIMP1, FN and MMP9 in ovarian tissue.
