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| Effect of umbilical cord mesenchymal stem cells on the regulation of apoptosis of theca cells by NR4A1 in primary ovarian insufficiency |
| BAI Lanlan1,2 , LUO Qianqian3, LIU Ranran4, ZHANG Hongqin1* |
1 Department of Histology andEmbryology,School of Basic Medical Sciences,Binzhou Medical University,Yantai 264003,Shandong,P.R.China;
2 Yantai Central Blood Station;
3 Morphology Laboratory, School of Basic Medical Sciences, Binzhou Medical University;
4 Department of Reproductive Medicine, Yantai Affiliated Hospital of Binzhou Medical University |
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Abstract Objective To investigate the therapeutic effects of umbilical cord mesenchymal stem cells (UCMSCs) on (primary ovarian insufficiency) POI rats and the mechanism of NR4A1 expression in the theca-interstitial cells (TICs) during the treatment. Methods Female Wistar rats of 5 weeks old were randomly divided into control group, POI group and POI+UCMSCs group. POI group was intraperitoneally injected with cis-platin (CP), and the control group was intraperitoneally injected with 0.9% saline, following with 7 days. POI+UCMSCs were treated with CP for 1 week, and then UCMSCs suspension was injected into the tail vein. One week later, the levels of E2 and FSH in the serum of the three groups were detected by enzyme-linked immunosorbent assay (ELISA). The morphological changes of ovaries were observed by HE staining. The apoptosis of granulosa
cells was detected by TUNEL. In addition, TICs were cultured in vitro and NR4A1 was expressed in TICs. CP and UCMSCs were treated into TICs and western blot was used to detect the levels of NR4A1 expression. Annexin V-FITC apoptosis assay kit was used to detect the apoptosis of TICs. Results Compared with the control group, the ovary of POI group was atrophy and the number of follicles in the ovary was significantly reduced(P<0.05), following the “luteal-like” structure being increased significantly(P<0.05). The number of follicles in the ovary increased significantly after UCMSCs treatment(P<0.05). Compared with the control group,the serum E2 level in the POI group was significantly decreased(P<0.01), while the FSH level was significantly increased(P<0.05). Compared withthe POI group, the serum E2 level was increased and the FSH level was decreased by UCMSCs treatment(P<0.05). Compared with the control group, the apoptosis of the granulosa cells in the POI group was significantly increased, while the UCMSCs could decrease the apoptosis of the granulosa cells(P<0.01). In addition, TICs cultured in vitro were fusiform and Cyp17a1 and NR4A1 were expressed, but FSHR expressed negative(P<0.05). After CP treatment, the NR4A1level was significantly decreased, and the apoptosis of TICs was significantly increased. After treatment with UCMSCs, the expression of NR4A1 was increased, but the apoptosis of TICs was significantly decreased(P<0.01). Conclusion UCMSCs could restore the ovarian function of POI by regulating the NR4A1 level of TICs expression and increase the regulation of TICs on granulosa cell apoptosis. This could provide a certain theoretical and experimental basis about the treatment of UCMSCs in POI.
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Received: 24 August 2019
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