Testicular heating suppresses spermatogenesis which is marked by germ cell loss via apoptotic pathways. Recently, it is reported that autophagy also can be induced by heat treatment in somatic cells. In this study, the status of autophagy in germ cells after heat treatment, as well as the partnership between autophagy and apoptosis in these cells was investigated. The results demonstrated that besides initiating apoptotic pathways, heat also induced autophagic pathways in germ cells. Exposure of germ cells to hyperthermia resulted in several specific features of the autophagic process, including autophagosome formation and the conversion of LC3-I to LC3-II. Furthermore, the ubiquitin-like protein conjugation system was implicated as being likely responsible for heat-induced autophagy in germ cells since all genes involving this system were found to be expressed in the testes. In addition, the upstream protein in this system, Atg7 (Autophagy-related gene 7), was found to be expressed in all types of spermatogenic cells, and its expression level was positively correlated with the level of autophagy in germ cells. As a result, Atg7 was selected as the investigative target to further analyze the role of autophagy in heat-induced germ cell death. It was shown that down expression of Atg7 protein resulted in the notable decrease in the level of autophagy in heat-treated germ cells, and this down-regulation of autophagy caused by Atg7 knockdown further reduced the apoptotic rate of germ cells. These results suggest that autophagy plays a positive role in the process of germ cell apoptosis after heat treatment. In conclusion, this study demonstrates that heat triggers autophagy and apoptosis in germ cells. These two mechanisms might act as partners, not antagonist, to induce cell death and lead to eventual destruction of spermatogenesis.
Objective Endometrial thickness is a prognostic factor for successful pregnancy. This meta-analysis aimed to examine the role of sildenafil citrate on infertile women with a thin endometrium. Methods Two investigators independently searched the literature on sildenafil citrate and infertile women with a thin endometrium from PubMed, EMBASE, and the Cochrane Controlled Trials Register Database from inception to January 2019. Results Nine studies involving 1452 patients were included for analysis in our study. We found that endometrial thickness in patients who received sildenafil citrate was significantly higher than that in the control group (placebo or no treatment) (weighted mean difference: 1.22; 95% confidence interval [CI]: 1.07–1.38). The radial artery resistance index was significantly lower (weighted mean difference: −0.12; 95% CI: −0.17 to −0.06), and the clinical pregnancy rate (risk ratio: 1.31; 95% CI: 1.11–1.53) and biochemical pregnancy rate (risk ratio: 1.45; 95% CI: 1.11–1.89) were significantly higher in the sildenafil citrate group compared with the control group. Conclusion Sildenafil citrate is effective in improving endometrial thickness, the clinical pregnancy rate, and the biochemical pregnancy rate in women who have a thin endometrium. This treatment is a potential therapeutic intervention for a thin endometrium.
Male macaques produce faster sperm than male humans due to a higher pressure of sperm competition in macaques. To explore the molecular basis of this biological difference, we firstly constructed macaque and human sperm proteomes using LC-MS/MS. We then detected the positively selected genes specifically on the branch of macaque based on branch-site likelihood method. We identified 197 positively selected genes specifically on the branch of macaque that are unselected in corresponding human orthologs. These genes are highly associated with mitochondria and axoneme that directly drive sperm motility. We further compared the ultrastructural differences of the midpiece between macaque and human sperms to provide evidence for our findings using transmission electron microscopy. In conclusion, our results provide potential molecular targets for explaining the different phenotypes under sperm competition between macaques and humans, and also provide resources for the analysis of male fertility.
ObjectivesTo investigate the incidence of functional ovarian cysts, its influence on clinical rates, and proper management after depot gonadotropin-releasing hormone (GnRH) agonist pretreatment in artificial frozen-thawed embryo transfer cycles (AC-FET).MethodsThis retrospective cohort study involved 3375 AC-FET cycles with follicular-phase depot GnRH agonist administration between January 2017 and December 2020. Subjects were divided into a study group (cycles with cyst formation) and a control group (cycles without cyst formation). The study group was matched by propensity scoring matching with the control group at a ratio of 1:2. For patients with ovarian cyst formation, two major managements were used: a conservative approach (i.e., expectant treatment) and a drug approach (i.e., continued agonist administration). The primary outcome was live birth rate (LBR).ResultsThe incidence of functional ovarian cysts following pituitary downregulation is 10.1% (341/3375). The study group exhibited a LBR similar to the control group (54.5% vs. 50.1%, adjusted odds ratio [aOR] 1.17, 95% confidence interval [CI] 0.88–1.56, P = 0.274). Patients with a lower body mass index and anti-Müllerian hormone, and a higher basal estradiol level were more susceptible to developing functional ovarian cysts. The LBR decreased after the drug approach compared with the conservative approach, but not significantly (aOR 0.63, 95% CI 0.35–1.14, P = 0.125). Following the conservative approach, cycles arrived at live births had a significantly shorter duration from the detection of functional cysts to the start of endometrium preparation (15.7 ± 5.1 days vs. 17.4 ± 5.3 days, P = 0.009) and a significantly higher proportion of ovarian cysts on the initial day of exogenous hormone supplementation (51.4% vs. 30.3%, P = 0.001). After controlling for all confounders, the differences remained statistically significant.ConclusionsIt is unnecessary to cancel cycles that experience functional ovarian cyst formation. Conservative management and further agonist suppression protocol had similar pregnancy rates. However, a conservative approach was recommended due to its lower cost and fewer side effects. Our findings support a shorter waiting period when choosing the conservative protocol.
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