title: Diet-induced obesity impairs spermatogenesis: a potential role for autophagy.
abstract: Autophagy is an evolutionarily conserved process that plays a crucial role in maintaining a series of cellular functions. It has been found that autophagy is closely involved in the physiological process of spermatogenesis and the regulation of sperm survival and motility. However, the role of autophagy in high-fat diet (HFD)-induced impaired spermatogenesis remains unknown. This study was designed to investigate the role of autophagy in HFD-induced spermatogenesis deficiency and employed chloroquine (CQ) to inhibit autophagy and rapamycin (RAP) to induce autophagy. 3-methyladenine (3-MA) and CQ were administered via intratesticular injection in vivo. The effects of CQ and 3-MA on the parameters of spermatozoa co-cultured with palmitic acid (PA) in vitro were also investigated. Human semen samples from obese, subfertile male patients were also collected to examine the level of autophagy. The results suggested that HFD mice subjected to CQ showed improved spermatogenesis. Inhibiting autophagy with CQ improved the decreased fertility of HFD male mice. Moreover, the in vivo and in vitro results indicated that both CQ and 3-MA could suppress the pathological changes in spermatozoa caused by HFD or PA treatment. Additionally, the excessive activation of autophagy was also observed in sperm samples from obese, subfertile male patients.
authors.affiliation: Reproductive Medicine Center, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Mu
authors.affiliation: Reproductive Medicine Center, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Yan
authors.affiliation: Reproductive Medicine Center, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Tai-Lang
authors.initials: TL
authors.lastname: Yin
authors.affiliation: Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Reproductive Medicine Center, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Reproductive Medicine Center, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology*; D059305:Diet, High-Fat / Q000009:adverse effects*; D006801:Humans; D007248:Infertility, Male / Q000150:complications / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D019308:Palmitic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D055101:Semen Analysis; D020123:Sirolimus / Q000494:pharmacology; D013091:Spermatogenesis / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013737:Testis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D019308:Palmitic Acid; C025946:3-methyladenine; D002738:Chloroquine; D000225:Adenine; D020123:Sirolimus