Signal transducer and activator of transcription (STAT) 1 and STAT3 are expressed in the human ovary and have Janus kinase 1-independent functions in the COV434 human granulosa cell line

Abstract

Ovarian granulosa cells are fundamental for oocyte maintenance and maturation. Recent studies have demonstrated the importance of members of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signalling pathway in the granulosa cell population of mouse and horse ovaries, with perturbation of JAK1 signalling in the mouse shown to impair oocyte maintenance and accelerate primordial follicle activation. The presence and role of the JAK/STAT pathway in human granulosa cells has yet to be elucidated. In this study, expression of JAK1, STAT1 and STAT3 was detected in oocytes and granulosa cells of human ovarian sections from fetal (40 weeks gestation) and premenopausal ovaries (34–41 years of age; n=3). To determine the effects of JAK1 signalling in granulosa cells, the human granulosa-like cell line COV434 was used, with JAK1 inhibition using ruxolitinib. Chemical inhibition of JAK1 in COV434 cells with 100nM ruxolitinib for 72h resulted in significant increases in STAT3 mRNA (P=0.034) and p-Y701-STAT1 protein (P=0.0117), demonstrating a role for JAK1 in modulating STAT in granulosa cells. This study implicates a conserved role for JAK/STAT signalling in human ovary development, warranting further investigation of this pathway in human granulosa cell function.

Bioinformatic analysis confirms differences in circular RNA expression profiles of cumulus cells between patients with ovarian and peritoneal endometriosis-associated infertility

“…Some findings have revealed the involvement of the JAK-STAT pathway in follicular development in mares and mice (47,48). Furthermore, Frost et al confirmed that the JAK-STAT signaling pathway contributes to the crosstalk between oocytes and CCs in humans using the COV434 cell line (49). Another enriched pathway is the TGF-b signaling pathway, which is reported to mediate the activation of primordial follicles, folliculogenesis, and oocyte-CC communication (50).…”

Bioinformatics and integrated pharmacology network to identify the therapeutic targets and potential molecular mechanism of alpha‐lipoic acid on primary ovarian insufficiency

“…STAT1 and STAT3, which belongs to the signal transducer and activator of transcription (STAT) family, are critical signaling molecules and transcriptional activator that regulate cell growth, survival, and proliferation 23 . STAT1 and STAT3 are expressed in granulosa cells, specifically in the primordial follicles 24 . Emerging evidence has shown that STAT3 prevents follicular atresia and enhances ovarian function in POI animal models 25,26 .…”

“…23 STAT1 and STAT3 are expressed in granulosa cells, specifically in the primordial follicles. 24 Emerging evidence has shown that STAT3 prevents follicular atresia and enhances ovarian function in POI animal models. 25,26 The mitogen-activated protein kinase (MAPKs), members of the serine/threonine-protein kinase family, are involved in cell proliferation, differentiation, growth, and many other physiological processes.…”

Expression of long noncoding RNAs in the ovarian granulosa cells of women with diminished ovarian reserve using high-throughput sequencing

“…Several studies have demonstrated that the inhibition of the PI3K-AKT pathway leads to apoptosis and autophagy in OGCs [ 60 , 61 ]. The importance of the JAK/STAT signaling pathway in ovarian development and folliculogenesis in horses [ 67 ] and humans [ 68 ] has been demonstrated. Polyfluoroalkyl substances reduce the ovarian reserve and decrease endogenous hormone synthesis by activating the peroxisome proliferator-activated receptor (PPAR) pathway [ 69 ], which has been indicated as a new biomarker of follicular capacity [ 70 ].…”