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.

Relationship between DYNLT1 and Beclin1 expression and the fertilising potential of human spermatozoa

“…According to the present study, the significant increase of Beclin1 mRNA and protein expression in all infertile patients of different aetiology in comparison to healthy controls corresponds with the data of Mu et al (). They found that Beclin1 protein levels were increased in obese male patients with poor semen quality.…”

“…Therefore, autophagy can act as a double‐edged sword (Navarro‐Yepes et al, ). It was reported that autophagy is closely involved in the physiological process of spermatogenesis and the regulation of sperm survival and motility (Mu et al, ). In addition, it has a role in host defence responses against inflammation and microbial infections.…”

“…However, it can trigger apoptosis, which may lead to oligozoospermia and infertility. Moreover, autophagy regulates inflammation, which is closely related to male spermatogenesis disorders (Mu et al, ). Alterations in the autophagic cycle rate are commonly observed in response to oxidative stress (Kroemer, Mariño, & Levine, ).…”

Iron and Advanced Glycation End Products: Emerging Role of Iron in Androgen Deficiency in Obesity

“…In our current rat experiment, the addition of 50% HFD or HFD plus ferric iron did not reduced the size of testis compared with healthy lean rats. It is likely that our experimental obese rats were healthier and had less severe testicle damage compared to those mice of Mu [52]. However, the addition of >1 g ferric iron plus HFD diet significantly decreased total T levels and this was associated with increased serum MDA levels, but not serum CML.…”

“…Although obese rats had slightly higher serum CML levels than those of lean rats, we found no difference in HbA1c level (lean: 4.3% vs. 4.5%). Mu et al [52] conducted a 8 weeks HFD feeding experiment and observed that serum T levels in obese mice were initially increased then gradually decreased and the reduction of total T levels was correlated with the decreased size of testis. In our current rat experiment, the addition of 50% HFD or HFD plus ferric iron did not reduced the size of testis compared with healthy lean rats.…”