Human placenta‐derived mesenchymal stem cells inhibit apoptosis of granulosa cells induced by IRE1α pathway in autoimmune POF mice

Abstract

Previous studies have shown that the ovarian failure in autoimmune‐induced premature ovarian failure (POF) mice could be improved by the transplantation of human placenta‐derived mesenchymal stem cells (hPMSCs); however, the protective mechanism of hPMSCs transplantation on ovarian dysfunction remains unclear. Ovarian dysfunction is closely related to the apoptosis of granulosa cells (GCs). To determine the effects of hPMSCs transplantation on GCs apoptosis, an autoimmune POF mice model was established with zona pellucida glycoprotein 3 (ZP3) peptide. It is reported that the inositol‐requiring enzyme 1α (IRE1α) and its downstream molecules play a central role in the endoplasmic reticulum (ER) stress‐induced apoptosis pathway. So the aim of this study is to investigate whether hPMSCs transplantation attenuated GCs apoptosis via inhibiting ER stress IRE1α signaling pathway. The ovarian dysfunction, follicular dysplasia, and GCs apoptosis were observed in the POF mice. And the IRE1α pathway was activated in ovaries of POF mice, as demonstrated by, increased X‐box binding protein 1 (XBP1), up‐regulated 78 kDa glucose‐regulated protein (GRP78) and caspase‐12. Following transplantation of hPMSCs, the ovarian structure and function were significantly improved in POF mice. In addition, the GCs apoptosis was obviously attenuated and IRE1α pathway was significantly inhibited. Transplantation of hPMSCs suppressed GCs apoptosis‐induced by ER stress IRE1α signaling pathway in POF mice, which might contribute to the hPMSCs transplantation‐mediating ovarian function recovery.

Mesenchymal Stem Cells as a Bio Organ for Treatment of Female Infertility

“…The same study also revealed that the PI3K/Akt signaling pathway contributes to the effects of PMSC transplantation on ovarian function (124)(125)(126). Another study reported that PMSC transplantation decreased GCs apoptosis through inhibition of the endoplasmic reticulum (ER) stress inositol-requiring enzyme 1 (IRE1) signaling pathway, thereby improving ovarian structure and function in POF mice (127). Furthermore, PMSC transplantation was shown to improve ovarian function in ovariectomized rats by inducing the production of estrogen and the expression of folliculogenesis-related genes (128).…”

Recent trends in stem cell therapy for premature ovarian insufficiency and its therapeutic potential: a review

“…Another therapeutic mechanism to prevent ovarian failure is to inhibit GC apoptosis. hPMSCs can inhibit GC apoptosis by modulating stress levels controlled by the IRE1α pathway [35]. One of the newest therapeutic approaches is to use stem cells extracted from human menstrual blood.…”

Protective roles and mechanisms of rosmarinic acid in cyclophosphamide‐induced premature ovarian failure

“…Accumulating research has confirmed that POF is related to accelerated follicular atresia, which primarily results from the apoptosis of GCs. [ 41 ] Excessive apoptosis can lead to a variety of ovarian diseases, including POF. [ 42 ] To further investigate the antiapoptotic mechanism of RA, the expression of cytochrome c and caspase‐3 was detected by western blot analysis and IHC.…”