N-acetylcysteine ameliorates erectile dysfunction in rats with hyperlipidemia by inhibiting oxidative stress and corpus cavernosum smooth muscle cells phenotypic modulation

Hyperlipidemia is a major risk factor for erectile dysfunction(ED).Oxidative stress and phenotypic modulation of corpus cavernosum smooth muscle cells(CcSMCs)are the key pathological factors of ED.N-acetylcysteine(NAC)can inhibit oxidative stress;however,whether NAc can alleviate pathological variations in the corpus cavernosum and promote erectile function recovery in hyperlipidemic rats remains unclear.A hyperlipidemia model was established using 27 eight-week-old male Sprague-Dawley(SD)rats fed a high-fat and high-cholesterol diet(hyperlipidemic rats,HR).In addition,9 male SD rats were fed a normal diet to serve as controls(NC).HR rats were divided into three groups:HR,HR+normal saline(NS),and HR+NAC(n=9 for each group;NS or NAc intraperitoneal injections were administered daily for 16 weeks).Subsequently,the lipid profiles,erectile function,oxidative stress,phenotypic modulation markers of ccsMCs,and tissue histology were analyzed.The experimental results revealed that erectile function was significantly impaired in the HR and HR+NS groups,but enhanced in the HR+NAC group.Abnormal lipid levels,over-activated oxidative stress,and multi-organ lesions observed in the HR and HR+NS groups were improved in the HR+NAC group.Moreover,the HR group showed significant phenotypic modulation of CCSMCs,which was also inhibited by NAC treatment.This report focuses on the therapeutic effect of NAc in restoring erectile function using a hyperlipidemic rat model by preventing CcSMC phenotypic modulationand attenuating oxidativestress.

Phosphoribosyl-pyrophosphate synthetase 2 (PRPS2)depletion regulates spermatogenic cell apoptosis and is correlated with hypospermatogenesis

Phosphoribosyl-pyrophosphate synthetase 2(PRPS2)is a rate-limiting enzyme and plays an important role in purine and pyrimidine nucleotide synthesis.Recent studies report that PRPS2 is involved in male infertility.However,the role of PRPS2 in hypospermatogenesis is unknown.In this study,the relationship of PRPS2 with hypospermatogenesis and spermatogenic cell apoptosis was investigated.The results showed that PRPS2 depletion increased the number of apoptotic spermatogenic cells in vitro.PRPS2 was downregulated in a mouse model of hypospermatogenesis.When PRPS2 expression was knocked down in mouse testes,hypospermatogenesis and accelerated apoptosis of spermatogenic cells were noted.E2F transcription factor 1(E2F1)was confirmed as the target gene of PRPS2 and played a key role in cell apoptosis by regulating the P53/Bcl-xl/Bcl-2/Caspase 6/Caspase 9 apoptosis pathway.Therefore,these data indicate that PRPS2 depletion contributes to the apoptosis of spermatogenic cells and is associated with hypospermatogenesis,which may be helpful for the diagnosis of male infertility.