Andrology最新文献

Background: Although some studies suggest that sleep deprivation may affect ejaculation regulation, related research is limited, and the mechanisms remain unclear.

Aim: This study aimed to explore whether sleep deprivation influences ejaculation regulation through amyloid-beta and to investigate its potential mechanisms.

Materials and methods: Normal ejaculating rats were randomly distributed into three separate groups for the study, and treated with sleep deprivation combined with saline gavage, sleep deprivation combined with sodium butyrate gavage, and control with saline gavage. The levels of amyloid-beta and 5-HT_1A receptors were assessed through Western blotting, PCR, and immunohistochemical techniques. The levels of interleukin-4 and serotonin (5-hydroxytryptamine) in the brain were determined by enzyme-linked immunosorbent assay.

Results: The experiment showed that the rats in the sleep deprivation combined with saline gavage group rats had a significantly faster ejaculation compared to the control combined with saline gavage group rats. Meanwhile, sleep deprivation combined with saline gavage group had the highest levels of amyloid-beta oligomers in the brain tissue. Correlation results revealed that the levels of amyloid-beta oligomers in brain tissue were inversely related to ejaculation latency and positively associated with ejaculation frequency. Furthermore, we found that elevated levels of amyloid-beta oligomers in brain tissue led to upregulation of 5-HT_1A receptor expression. Additionally, elevated levels of amyloid-beta oligomers in brain tissue were found to increase interleukin-4 levels, thereby reducing 5-hydroxytryptamine levels.

Discussion: Sleep deprivation indeed accelerates ejaculation, and this acceleration is closely related to amyloid-beta. Sleep deprivation can increase amyloid-beta levels in brain tissue, mediating a decrease in 5-hydroxytryptamine levels and overexpression of 5-HT_1A receptors, thereby accelerating ejaculation.

Conclusion: There is a significant correlation between elevated amyloid-beta levels in brain tissue because of sleep deprivation and accelerated ejaculation. This study's main findings offer insights into the development of acquired premature ejaculation linked to poor sleep and establish a theoretical framework for investigating potential treatments for this condition.

Background: Current advances in high-throughput sequencing technology enable the precise identification of Y chromosome microdeletion and primary duplication in infertile couples, but the mechanism and clinical significance of these mutations in assisted reproductive techniques remain unclear.

Objectives: To investigate the effects of AZFc (b2/b4, b1/b3, b2/b3, and gr/gr) deletions and primary duplications on the outcomes of the first intracytoplasmic sperm injection (ICSI) treatment cycle.

Methods: Y chromosome microdeletions and primary duplications in infertile men were detected using next-generation sequencing (NGS) technology. A total of 813 patients undergoing their first ICSI treatment were divided into six groups: b2/b4 deletion group (n = 28), three partial AZFc subdeletion groups (b1/b3, n = 13; b2/b3, n = 72; gr/gr, n = 71), primary AZFc duplication group (n = 54), and control group with a normal Y chromosome (n = 575). The multivariate logistic regression analyses were conducted to assess and compare the embryologic and cumulative reproductive outcomes of ICSI treatment across these groups.

Results: Compared with the control group, the b2/b4 deletion group showed a poor ICSI embryologic outcome after ICSI treatment, with a significantly lower fertilization rate per oocytes retrieval (72.22% vs.79.89%; adjusted odds ratio [OR], 0.63; 95% confidence interval [CI], 0.45-0.88, p < 0.01) and 2 pronuclear (2PN) fertilization rate (66.37% vs. 74.80%; adjusted OR, 0.65; 95% CI, 0.47-0.89, p < 0.01) either before or after adjustment for confounding factors. Nevertheless, three partial AZFc deletion groups showed no effect on the ICSI fertilization rate after ICSI treatment. The primary AZFc duplication group had a significantly lower clinical pregnancy rate per transferred embryo (56.25% vs. 65.97%; adjusted OR, 0.64; 95% CI, 0.41-0.99, p < 0.05), and the semen characteristics varied from azoospermia to normozoospermia. In addition, all indicators related to embryo quality, clinical pregnancy, and live birth outcomes in the primary duplication group were inferior to those in the control group.

Conclusion: This study indicates that b2/b4 deletion has a negative effect on ICSI outcomes, particularly the fertilization rates. Partial AZFc deletions have no significant effect on the fertilization rate after ICSI treatment. Primary AZFc duplication can lead to varying seminal phenotypes and has a negative effect on ICSI embryologic and pregnancy outcomes, particularly showing a significant association with low birth weight in newborns after ICSI treatment.

Background: Diabetes mellitus-induced erectile dysfunction (DMED) responds poorly to first-line treatments, necessitating the development of new therapeutic strategies. Relaxin-2 (RLX-2) plays a crucial role in protecting vascular endothelium, vasodilatation, and antifibrosis in various diseases. However, its effects and mechanisms on DMED remain unclear.

Objectives: To investigate the effects and mechanisms of RLX-2 on DMED rats in vivo and vitro.

Methods: For in vivo research, 30 Sprague-Dawley rats were allocated into three groups: control, DMED, and DMED + RLX-2. The induction of DMED in the rats was achieved through intraperitoneal administration of streptozotocin, with confirmation of ED status being conducted via the apomorphine test. Rats in the DMED + RLX-2 group received continuous RLX-2 treatment by osmotic pump. Following a 4-week treatment period, assessment of erectile function was carried out using cavernous manometry, and samples of corpus cavernosum tissues were procured for subsequent analysis. For in vitro research, human cardiac microvascular endothelial cells (HCMECs) were allocated into three groups: control, high glucose (HG, 40 mM), and HG + RLX-2. HCMECs were cultured for 6 days and treated with RLX-2 for 48 h before collection for subsequent experiments.

Results: In DMED rats, RLX-2 treatment partially improved erectile function. We observed relatively normalized functions of endothelial and smooth muscle cells with decreased levels of apoptosis and fibrosis in the penis. In vitro experiments also demonstrated the antihyperglycemic effects of RLX-2.

Conclusions: RLX-2 can protect endothelial and smooth muscle function, and inhibit aberrant apoptosis and fibrosis in the corpus cavernosum, thereby improving erectile function in DMED rats. This may provide a novel treatment for DMED.

Background: Gonadotropins are glycoprotein hormones fundamental in the endocrine regulation of reproduction. They act on structurally similar members of G protein-coupled receptors (GPCRs) expressed exclusively in the gonads and support gametogenesis, sex steroid synthesis, and pregnancy. While it is a common opinion that the gonadotropin receptors act as a single molecule entity (monomer), increasing evidence underlines the formation of molecular complexes involving multiple receptors.

Objectives: To review current knowledge of membrane receptor-receptor interactions in reproduction.

Results and discussion: Homo/heteromers of gonadotropin receptors may act as allosteric modulators, act as biased agonist and/or cooperate in sustaining intracellular signals fundamental to support reproduction. Technical limitations lead to in vitro data that require to be confirmed in vivo to figure out the physiological impact of gonadotropin receptor assemblies.

Conclusions: Gonadotropin receptor homo/heteromers provide a new field of research that deserves attention for possible clinical and therapeutic implications in physiology and pathophysiology.

Background: Over the past few decades, several studies have found that semen quality parameters have steadily declined over time. Many hypotheses have been made to explain this finding, among which a sedentary lifestyle has been investigated. To synthesize the current evidence, we performed a systematic review of published papers reporting on the relationship between sedentary habits and semen parameters.

Methods: Embase and PubMed were systematically searched for papers published in English up to May 2023. We included all full-text observational papers that reported the relationship between sedentariness and semen parameters. Article selection adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.

Results: Sixteen observational studies were ultimately included, six in healthy men and ten in men from Fertility Clinics. They encompassed a total of 13,509 men, with 9877 being healthy men and 3632 presenting at Fertility Clinics for initial assessment. In terms of semen volume, no association emerged in the six studies involving healthy men: however, results in men referring to fertility clinics mainly showed no association, with one indicating a decline and one higher volume. Twelve studies did not report differences in sperm concentration, while one study in men from Fertility Clinics and two in healthy men observed a decline in this parameter with increasing time spent on TV watching or sedentary posture in spare time. Total sperm count was found to be similar across groups of inactivity, except for one study that showed a significant decrease when men from Fertility Clinics spent more time watching TV. No significant differences were reported in sperm motility across all studies, with only one study, among those addressing sperm morphology, indicating a lower percentage of normal forms in men watching TV more than 3 h per day. Finally, three studies conducted in men referring to Fertility Clinics analyzed the sperm DNA fragmentation index. Two of these studies found a higher DNA fragmentation index in men spending more time per day in a sitting posture.

Conclusions: This review suggests a weak association between time spent sitting during spare time and sperm concentration, but the findings are inconsistent, highlighting the need for further research.

Congenital absence of the vas deferens (CAVD) is a syndrome with a heterogeneous presentation: bilateral (CBAVD) or unilateral (CUAVD), complete or partial and associated or not with other anomalies of the male urogenital system. A turning point came in 1968 when CBAVD was associated with cystic fibrosis and its CFTR gene mutations. Genetic studies then revealed that a minority of CBAVD but a majority of CUAVD are CFTR-independent. In the literature, reference is classically made to two sources from the 18th and 19th century: Hunter and Reverdin. This scarcity prompted us to look for additional observations of CAVD. By a meticulous bibliographical search, we identified a corpus of 10 European observations (8 CUAVD and 2 CBAVD) some of them richly illustrated. They were collected between 1755 and 1876 throughout adult men autopsies. We also provided their primary and unambiguous sources. Analysis of the reported data revealed some interesting facts: both CBAVD cases were unlikely linked to cystic fibrosis and half of CUAVD cases were associated with an ipsilateral kidney absence, suggesting a CFTR-independent pathophysiology. Moreover, the anatomical details of the anomalies raise interesting embryological questions we have tried to address in the light of current data. This work made it possible to identify new historical sources dealing with male genital tract pathologies. It sheds light on the origins of andrology and opens up interesting prospects for research and education in the field.

Background: Dimethandrolone undecanoate (DMAU) is under development as a single agent hormonal male contraceptive. DMAU is a prodrug hydrolyzed by esterase(s) to the active metabolite dimethandrolone (DMA) which has dual androgenic and progestogenic actions. Phase 1 clinical trial results show DMAU to be well-tolerated as an oral contraceptive in healthy men; however, delivery of DMAU as a long-acting injectable rather than a daily oral formulation would provide user compliance benefits and address oral bioavailability concerns.

Objective: To assess the safety, pharmacokinetics (PK), and long-acting contraceptive potential of DMAU in male non-human primates (NHP) when delivered as an injectable or oral formulation.

Materials and methods: DMAU was administered to cynomolgus macaques orally for 9 months or as five weekly intramuscular (IM) injections and to rhesus macaques as a single IM injection. Evaluations of safety, fertility indicators, and serum levels of DMAU and DMA were followed > 2 years post-dose.

Results: Repeat dose oral and IM administrations were well-tolerated with no significant toxicological findings. Dramatic reductions in serum testosterone concentration occurred within days of administration followed by sustained suppression of additional fertility indicators (e.g., serum inhibin B, sperm count, and testicular spermatogenesis). Slight body weight increases and reductions in testes weight also occurred. Repeat DMAU injections resulted in DMA serum concentrations above the lower limit of quantification (1 ng/mL) for > 500 days. DMAU PK parameters increased with increasing IM dose, while dose dependence was not seen for serum DMA concentrations suggesting a depot effect with a reservoir of non-circulating prodrug remaining at the injection site which gets slowly hydrolyzed to DMA and absorbed into circulation. Testosterone levels and spermatogenesis returned by the end of the recovery period.

Conclusions: Nonclinical safety, PK, and pharmacodynamic data in male NHP demonstrate the safe, well-tolerated, long-acting, and reversible contraceptive potential of injectable DMAU.

Background: The most prevalent sexually transmitted disease in the world has the human papillomavirus (HPV) as its etiological agent.

Objectives: To evaluate the prevalence of previous and actual HPV infection and the clinical manifestations in unselected males.

Materials and methods: A total of 718 males participating to a surveillance program were asked to complete a study visit at our unit, including semen collection, balanopreputial sulcus swab, and blood collection for total anti-HPV immunoglobulin G (IgG). When HPV-DNA was detected, we performed HPV fluorescence in situ hybridization, oral and anal swab, and penoscopy. Because previous studies demonstrated a very high risk for HPV infection in subjects with history of HPV-induced lesions, with a partner with diagnosed HPV infection or reporting couple infertility or sexual promiscuity and an increase of the risk in males having sex with males, in subjects with unprotected sexual intercourses or in heavy smokers, patients were therefore stratified according to the presence of these known risk factors (RFs).

Results: Actual HPV infection was detected in 401/718 subjects (55.85%). Oral HPV-DNA was reported in 80 subjects and anal HPV infection in 52 subjects. Anti-HPV IgG antibodies have been detected in 288 subjects. The overall prevalence of HPV exposition, considering actual and/or previous infection was 77.99%. Among infected men, high-risk HPV genotypes were detected in 66.08%. A total of 514 subjects were considered as the RF population, while 150 were classified in the non-RF population. There was a significantly higher prevalence of condylomatosis (odds ratio [OR] 4.07) and of seminal infection (OR 6.22) in the RF group.

Discussion and conclusion: These data represent an alert for the healthcare system to perform informative and screening campaigns for HPV infection in males and to promote HPV vaccination both in young people and for adult males with RF for HPV infections.