Sodium 4-phenylbutyrate Attenuates High-fat Diet-induced Impaired Spermatogenesis

To determine the mitigating effects of sodium 4-phenylbutyrate (4-PBA) on high-fat diet (HFD)-induced spermatogenesis dysfunction. Male rats (n = 30) were randomly divided into three groups: control, HFD, and 4-PBA (HFD+4-PBA). After 13 weeks, rats were euthanized. Testes and epididymis were harvested for further analysis. Sex hormones were detected, and hematoxylin and eosin staining was performed to examine the histological changes in the testes. Semen samples were collected to evaluate sperm quality. Spermatogenic cell apoptosis was detected by TUNEL assay. Compared with the control group, the final body weight and body weight gain were significantly higher in HFD-fed rats, while the testicle/body weight ratios were lower (P < 0.05). In HFD-fed rats, obvious pathological changes in the testicular tissue were observed. Treatment with 4-PBA attenuated HFD-induced histological damage, ameliorated the HFD-induced decrease in serum testosterone (T), and reduced the rate of testicular cell apoptosis (P < 0.05) in obese male rats. Finally, 4-PBA significantly improved semen parameters in HFD rats (P < 0.05). HFD exposure induced detrimental effects on spermatogenesis, semen quality, serum T level, and testicular cell apoptosis in rats. Treatment with 4-PBA ameliorated HFD-induced impaired spermatogenesis via inhibition of apoptosis in rats. 4-PBA may have therapeutic value in the treatment of obesity-related impairment of spermatogenesis.