Open AccessOncostatin M inhibits differentiation of rat stem Leydig cells in vivo and in vitro
Author(s) -
Wang Yiyan,
Xie Lubin,
Tian Erpo,
Li Xiaoheng,
Wen Zina,
Li Linchao,
Chen Lanlan,
Zhong Ying,
Ge RenShan
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13946
Subject(s) - leydig cell , oncostatin m , seminiferous tubule , biology , endocrinology , medicine , luteinizing hormone , stem cell , microbiology and biotechnology , cellular differentiation , cytokine , interleukin 6 , hormone , immunology , sertoli cell , spermatogenesis , biochemistry , gene
Oncostatin M ( OSM ) is a pleiotropic cytokine within the interleukin six family of cytokines, which regulate cell growth and differentiation in a wide variety of biological systems. However, its action and underlying mechanisms on stem Leydig cell development are unclear. The objective of the present study was to investigate whether OSM affects the proliferation and differentiation of rat stem Leydig cells. We used a Leydig cell regeneration model in rat testis and a unique seminiferous tubule culture system after ethane dimethane sulfonate ( EDS ) treatment to assess the ability of OSM in the regulation of proliferation and differentiation of rat stem Leydig cells. Intratesticular injection of OSM (10 and 100 ng/testis) from post‐ EDS day 14 to 28 blocked the regeneration of Leydig cells by reducing serum testosterone levels without affecting serum luteinizing hormone and follicle‐stimulating hormone levels. It also decreased the levels of Leydig cell‐specific mRNA s ( Lhcgr , Star , Cyp11a1 , Hsd3b1, Cyp17a1 and Hsd11b1 ) and their proteins by the RNA ‐Seq and Western blotting analysis. OSM had no effect on the proliferative capacity of Leydig cells in vivo. In the seminiferous tubule culture system, OSM (0.1, 1, 10 and 100 ng/mL) inhibited the differentiation of stem Leydig cells by reducing medium testosterone levels and downregulating the expression of Leydig cell‐specific genes ( Lhcgr , Star , Cyp11a1 , Hsd3b1, Cyp17a1 and Hsd11b1 ) and their proteins. OSM ‐mediated action was reversed by S3I‐201 (a STAT 3 antagonist) or filgotinib (a JAK 1 inhibitor). These data suggest that OSM is an inhibitory factor of rat stem Leydig cell development.