The relationship between circulating metabolites and prostate hyperplasia: a Mendelian randomization study.

BACKGROUND: Circulating metabolites (CM) play a pivotal role in our overall health, yet the current evidence concerning the involvement of diverse CM in benign prostatic hyperplasia (BPH) remains limited. Mendelian randomization (MR) offers a promising avenue to explore the potential impact of CM on BPH. METHODS: In a forward MR analysis, a cohort of 249 circulating metabolites was employed as exposures to investigate their potential associations with BPH risk. Conversely, in a reverse MR analysis, BPH was employed as an exposure to assess its effects on CM. RESULTS: The forward MR analysis discerned a linkage between six metabolites and BPH, with careful consideration to excluding heterogeneity and pleiotropy. Subsequently, the reverse MR analysis unveiled that nine metabolic compounds, mainly comprising phospholipids and triglycerides, potentially exhibit elevated levels in BPH patients. CONCLUSION: Bidirectional MR analysis furnishes genetic insight into the interplay between CM and BPH. The prominence of lipids and triglycerides emerges as significant factors intricately linked to BPH risk.

[Impacts of the expressions of Fas and FasL mRNA and proteins on sperm concentration and motility].

Objective: To investigate the influence of the expressions of apoptosis-related Fas and FasL mRNA and proteins on sperm concentration and motility. METHODS: We collected semen samples from 80 adult males and divided them into four groups of an equal number according to sperm concentration and the percentage of progressively motile sperm (PMS): normal, asthenospermia (AS), oligozoospermia (OS) and oligoasthenospermia (OAS). We examined the routine semen parameters, the levels of Fas and FasL proteins and the expressions of Fas and FasL genes in different groups. RESULTS: The sperm concentrations in the normal, AS, OS and OAS groups were (68.11 ± 35.49), (92.21 ± 60.96), (8.55 ± 2.82) and (5.96 ± 3.80) ×106/ml, respectively, and the percentages of PMS were (49.40 ± 13.86)%, (22.12 ± 7.13)%, (40.77 ± 8.41)% and (14.53 ± 9.74), respectively. The Fas protein level was significantly higher in the AS, OS and OAS than in the normal group (ï¼»425.03 ± 50.56ï¼½, ï¼»442.32 ± 84.88ï¼½ and ï¼»448.42 ± 84.79ï¼½ vs ï¼»381.07 ± 52.37ï¼½ pg/ml, P < 0.05), correlated negatively with sperm concentration (r = －0.377, P < 0.01) and PMS (r = －0.350, P < 0.01), but exhibited no statistically significant differences between the former three and latter group (ï¼»166.98 ± 27.39ï¼½, ï¼»169.51 ± 32.62ï¼½ and ï¼»171.46 ± 32.61ï¼½ vs ï¼»167.49 ± 29.91ï¼½ pg/ml, P > 0.05). The relative levels of the Fas gene in the normal, AS, OS and OAS groups were 1, (0.88 ± 1.17), (2.55 ± 2.11) and (0.69 ± 0.90) respectively, lower in the AS and OAS than in the normal group, and positively correlated with sperm motility; those of the FasL gene were 1, (1.99 ± 1.81), (2.08 ± 2.06) and (2.03 ± 2.23) respectively, higher in the OS and OAS than in the normal group, and negatively correlated with sperm motility. Compared with the normal group, the expressions of Fas and FasL were down-regulated in the AS but up-regulated in the OS group; the expression of Fas, however, was down-regulated and that of FasL up-regulated in the OAS group. The expression of Fas mRNA was positively correlated with the percentage of PMS (r = 0.355, P = 0.01) and total sperm motility (r = 0.358, P < 0.01), while sperm concentration negatively correlated with the expression FasL mRNA (r = －0.305, P < 0.05). There was no significant correlation between the other parameters. CONCLUSIONS: Fas and FasL are differentially expressed in normal, asthenospermia, oligozoospermia and oligoasthenospermia males. Their up-regulated expressions may promote the apoptosis of spermatogenic and sperm cells and induce oligozoospermia, while their down-regulated expressions may indicate the failure of abnormal spermatogenic and sperm cells to immediately undergo programmed death, which can be one of the causes of asthenospermia.