scholarly journals T reg deficiency‐mediated T H 1 response causes human premature ovarian insufficiency through apoptosis and steroidogenesis dysfunction of granulosa cells

2021 ◽  
Vol 11 (6) ◽  
Author(s):  
Xue Jiao ◽  
Xiruo Zhang ◽  
Nianyu Li ◽  
Dunfang Zhang ◽  
Shidou Zhao ◽  
...  
2020 ◽  
Vol 235 (11) ◽  
pp. 8826-8838
Author(s):  
Xinyue Zhang ◽  
Yujie Dang ◽  
Ran Liu ◽  
Shidou Zhao ◽  
Jinlong Ma ◽  
...  

Epigenomics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 319-332
Author(s):  
Xing-Yu Zhou ◽  
Ying Li ◽  
Jun Zhang ◽  
Yu-Dong Liu ◽  
Jing Zhe ◽  
...  

Aim: To identify the expression profiles and potential functions of circular RNAs (circRNAs) in granulosa cells (GCs) from women with biochemical premature ovarian insufficiency (bPOI). Patients & methods: CircRNAs microarray analysis was performed to GCs from 8 patients with bPOI and 8 control women, followed by qRT-PCR in 15 paired samples. CircRNA–miRNA networks and the prediction of their enriched signaling pathways were conducted by bioinformatics analysis. Results: A total of 133 upregulated and 424 downregulated circRNAs was identified in women with bPOI. We constructed circRNA–miRNA networks and found that the most predominantly enriched signaling pathways were the FoxO signaling pathway and cellular senescence. Conclusion: CircRNAs are differentially expressed in bPOI, which might contribute to the pathogenesis of bPOI.


2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Xing-Yu Zhou ◽  
Jun Zhang ◽  
Ying Li ◽  
Ying-Xue Chen ◽  
Xiao-Min Wu ◽  
...  

The mechanism underlying the role of oxidative stress and advanced oxidation protein products (AOPPs) in the aetiology of premature ovarian insufficiency (POI) is poorly understood. Here, we investigated the plasma AOPP level in POI patients and the effects of AOPPs on granulosa cells both in vitro and in vivo. KGN cells were treated with different AOPP doses, and cell cycle distribution, intracellular reactive oxygen species (ROS), and protein expression levels were measured. Sprague–Dawley (SD) rats were treated daily with PBS, rat serum albumin, AOPP, or AOPP+ N-acetylcysteine (NAC) for 12 weeks to explore the effect of AOPPs on ovarian function. Plasma AOPP concentrations were significantly higher in both POI and biochemical POI patients than in controls and negatively correlated with anti-Müllerian hormone and the antral follicle count. KGN cells treated with AOPP exhibited G1/G0-phase arrest. AOPP induced G1/G0-phase arrest in KGN cells by activating the ROS-c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK)-p21 pathway. Pretreatment with NAC, SP600125, SB203580, and si-p21 blocked AOPP-induced G1/G0-phase arrest. In SD rats, AOPP treatment increased the proportion of atretic follicles, and NAC attenuated the adverse effects of AOPPs in the ovary. In conclusion, we provide mechanistic evidence that AOPPs may induce cell cycle arrest in granulosa cells via the ROS-JNK/p38 MAPK-p21 pathway and thus may be a novel biomarker of POI.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Siwen Zhang ◽  
Boxian Huang ◽  
Peng Su ◽  
Qiyuan Chang ◽  
Pingping Li ◽  
...  

Abstract Background Premature ovarian insufficiency (POI) is one of the major causes of infertility. We previously demonstrated that transplantation of menstrual blood-derived stromal cells (MenSCs) effectively improved ovarian function in a murine model of POI. Recent studies indicated that mesenchymal stem cell-derived exosomes were important components in tissue repair. In this study, we investigated the therapeutic effects of MenSCs-derived exosomes (MenSCs-Exos) in a rat model of POI and its mechanism in restoring ovulation. Methods Ovaries of 4.5-day-old Sprague Dawley rats (SD rats) were cultured in vitro to evaluate the effects of MenSCs-Exos exposure on early follicle development. Furthermore, POI in rats was induced by intraperitoneal administration of 4-vinylcyclohexene diepoxide (VCD). Forty-eight POI rats were randomly assigned to four groups, each receiving a different treatment: PBS, MenSCs, MenSCs-Exos, and Exo-free culture supernatant of MenSCs. Estrous cyclicity, ovarian morphology, follicle dynamics, serum hormones, pregnancy outcomes, and molecular changes were investigated. Results Exposure to MenSCs-Exos promoted the proliferation of granulosa cells in primordial and primary follicles in vitro and increased the expression of early follicle markers Deleted In Azoospermia Like (DAZL) and Forkhead Box L2 (FOXL2) while inhibiting follicle apoptosis. In vivo, MenSCs-Exos transplantation effectively promoted follicle development in the rat model of POI and restored the estrous cyclicity and serum sex hormone levels, followed by improving the live birth outcome. In addition, transplantation of MenSCs-Exos regulated the composition of the ovarian extracellular matrix and accelerated the recruitment of dormant follicles in the ovarian cortex and increased proliferation of granulosa cells in these follicles. Conclusion MenSCs-Exos markedly promoted follicle development in vitro and in vivo and restored fertility in POI rats, suggesting a restorative effect on ovarian functions. The therapeutic effect of MenSCs-Exos transplantation was sustainable, consistent with that of MenSCs transplantation. Our results suggested that MenSCs-Exos transplantation may be a promising cell-free bioresource in the treatment of POI.


2019 ◽  
Author(s):  
Miomira Ivovic ◽  
Ljiljana Marina ◽  
Milina Tancic-Gajic ◽  
Zorana Arizanovic ◽  
Magdalena Stankovic ◽  
...  

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