title: IL-6 mediates differentiation disorder during spermatogenesis in obesity-associated inflammation by affecting the expression of Zfp637 through the SOCS3/STAT3 pathway.
abstract: Zfp637 is a recently identified zinc finger protein, and its functions remain largely unknown. Here, we innovatively demonstrate the effects of Zfp637 on the differentiation of mouse spermatogonia and on its downstream target gene SOX2 in vitro. Obesity has been recognized as a chronic inflammatory disease that leads to decreased sexual function and sexual development disorders. We observed higher levels of IL-6 in serum and testis homogenates from obese mice compared with control mice. We also demonstrated that high levels of IL-6 inhibited Zfp637 expression, and we elucidated the underlying mechanisms. SOCS3 overexpression and STAT3 phosphorylation inhibitor (AG490) were used to investigate the function of the SOCS3/STAT3 pathway during this process. Our results showed that exposure of mouse spermatogonial cells to high levels of IL-6 inhibited Zfp637 expression by increasing SOCS3 expression and inhibiting the phosphorylation of STAT3, further reducing cellular differentiation. Consistent with the in vitro results, we observed increasing expression levels of SOCS3 and SOX2, but a reduction of Zfp637 expression, in obese mouse testes. In conclusion, Zfp637 plays a crucial role in spermatogenesis by downregulating SOX2 expression, and IL-6 can decrease the expression of Zfp637 through the SOCS3/STAT3 signaling pathway.
authors.affiliation: Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Guizhen
authors.initials: G
authors.lastname: Huang
authors.affiliation: Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Yuan
authors.affiliation: Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Division of Experimental Oncology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Division of Experimental Oncology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China.
authors.forename: Di
authors.initials: D
authors.lastname: Gong
authors.affiliation: Division of Experimental Oncology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Experimental Oncology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Division of Experimental Oncology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Lin
authors.affiliation: Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Lugang
authors.initials: L
authors.lastname: Huang
mesh_terms: D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D007249:Inflammation / Q000209:etiology; D015850:Interleukin-6 / Q000032:analysis / Q000097:blood / Q000494:pharmacology*; D020738:Leptin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000150:complications / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013091:Spermatogenesis / Q000187:drug effects*; D013093:Spermatogonia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000235:genetics / Q000378:metabolism*; D013737:Testis / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D004268:DNA-Binding Proteins; D015850:Interleukin-6; D020738:Leptin; D055748:SOXB1 Transcription Factors; D050796:STAT3 Transcription Factor; C491411:Socs3 protein, mouse; C527783:Sox2 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D020032:Tyrphostins; C551671:Zfp637 protein, mouse; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide