Oncostatin M stimulates immature Leydig cell proliferation but inhibits its maturation and function in rats through JAK1/STAT3 signaling and induction of oxidative stress in vitro

Abstract

Background : Oncostatin M (OSM) is a member of the interleukin‐6 group of cytokines, which can regulate cell proliferation, growth, and function. Immature Leydig cells have the ability to proliferate and differentiate, and adult Leydig cells have the function of testosterone synthesis. However, the role and underlying mechanisms of OSM on the proliferation and function of Leydig cells remain unclear. Methods : The effects of OSM on the proliferation, apoptosis, and function of immature Leydig cells isolated from 35‐day‐old rats and the function of adult Leydig cells isolated from 63‐day‐old rats in vitro. Results : OSM stimulated immature Leydig cell proliferation after up‐regulating the expression of Ccnd1 and Cdk4 to drive the transition of G1 phase to M2 phase in the cell cycle at 10 and 100 ng/ml. OSM did not affect the apoptosis of immature Leydig cells up to 100 ng/ml. OSM inhibited testosterone production in immature and adult Leydig cells by down‐regulating the expression of Lhcgr, Star, Cyp11a1, Hsd3b1, and Cyp17a1 at 1–100 ng/ml. OSM induced reactive oxygen species and down‐regulated the expression of antioxidant genes and lowered mitochondrial membrane potential at 10 and 100 ng/ml in both Leydig cells. Janus kinase 1 (JAK1) antagonist filgotinib and signal transducer and activator of transcription 3 (STAT3) antagonist S3I‐201 reversed the effect of OSM, indicating that it acts on JAK1/STAT3 signaling. Conclusion : Oncostatin M stimulates immature Leydig cell proliferation while inhibiting the function of immature and adult Leydig cells.

Application of single-cell RNA sequencing on human testicular samples: a comprehensive review

“…For instance, Zhao et al found that in iNOA patients, Sertoli cells were basically in stage a and stage b (mentioned above), and they revealed iNOA SCs showed different gene expressions pattern compared with normal testes 55 , which were independently confirmed by Wang et al 76 and Chen et al 56 . In terms of somatic cells, two main somatic cells of the human testis, SCs and LCs, showed similar status in NOA patients, both were immature but with enhanced proliferative/divisive ability 55 , 78 , which were in line with the fact that immature somatic cells have proliferative ability 107 , 108 . Alfano et al further found that in SCOS (the severe pathology of NOA), the transcriptional and phenotypic features of LC were more like pre-pubertal LC, indicating the repressed maturation of LC in NOA 88 .…”

Protective role of autophagy in triptolide-induced apoptosis of TM3 Leydig cells

“…[27] Spermatogenesis from the proliferation and differentiation of undifferentiated spermatogonial stem cells is based on the complete function of the tissue structure. [28][29][30] In addition to supporting cells, Leydig cells play an important role in maintaining spermatogenesis [31][32][33] and are affected by various chemicals and drug metabolism. [34][35][36][37] TP is a widely used immunosuppressive agent that has adverse effects on the male reproductive system, as well as hepatotoxicity and nephrotoxicity.…”

Isolation of Leydig cells from adult rat testes by magnetic‐activated cell sorting protocol based on prolactin receptor expression

“…The manufacturers and the dilutions of the antibodies can be found in Table S1. All the antibodies used in the present study were used and validated by previous studies 20–25 . The primers for quantitative PCR (QPCR) are summarized in Table S2.…”

“…All the antibodies used in the present study were used and validated by previous studies. [20][21][22][23][24][25] The primers for quantitative PCR (QPCR) are summarized in Table S2.…”