Cannarella Rossella, Leanza Claudia, Crafa Andrea, Barbagallo Federica, La Vignera Sandro, Condorelli Rosita Angela, Calogero Aldo Eugenio
Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
Glickman Urological & Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
World J Mens Health. 2024 Jul;42(3):543-554. doi: 10.5534/wjmh.230094. Epub 2023 Sep 27.
The () gene is a paternally expressed imprinted gene that appears to play a role in embryo survival. The latest meta-analysis on methylation pattern in spermatozoa of infertile patients found higher methylation in spermatozoa from infertile patients than fertile controls. To provide an updated and comprehensive systematic review and meta-analysis on the gene methylation pattern in patients with abnormal sperm parameters compared to men with normal parameters.
This meta-analysis was registered in PROSPERO (CRD42023397056) and performed following the MOOSE guidelines for Meta-analyses and Systematic Reviews of Observational Studies and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). Only original articles evaluating gene methylation in spermatozoa from patients with infertility or abnormalities in one or more sperm parameters compared to fertile or normozoospermic men were included.
Of 354 abstracts evaluated for eligibility, only 6 studies were included in the quantitative synthesis, involving a total of 301 patients and 163 controls. Our analysis showed significantly higher levels of gene methylation in patients compared with controls (standard mean difference [SMD] 2.150, 95% confidence interval [CI] 0.377, 3.922; p=0.017), although there was significant heterogeneity between studies (Q-value=239.90, p<0.001; I²=97.91%). No significant evidence of publication bias was found, although one study was sensitive enough to skew the results, leading to a loss of significance (SMD 1.543, 95% CI -0.300, 3.387; p=0.101). In meta-regression analysis, we found that the results were independent of both ages (p=0.6519) and sperm concentration (p=0.2360).
Sperm DNA methylation may be associated with epigenetic risk in assisted reproductive techniques (ART). The gene could be included in the genetic panel of prospective studies aimed at identifying the most representative and cost-effective genes to be analyzed in couples undergoing ART.
（）基因是一个父系表达的印记基因，似乎在胚胎存活中起作用。关于不育患者精子甲基化模式的最新荟萃分析发现，不育患者精子中的甲基化水平高于生育力正常的对照组。旨在提供一项更新的、全面的系统评价和荟萃分析，以比较精子参数异常患者与精子参数正常男性的（）基因甲基化模式。
本荟萃分析已在PROSPERO（CRD42023397056）注册，并按照观察性研究的荟萃分析和系统评价的MOOSE指南以及系统评价和荟萃分析方案的首选报告项目（PRISMA-P）进行。仅纳入评估不育患者或一个或多个精子参数异常患者的精子中（）基因甲基化情况，并与生育力正常或精子正常的男性进行比较的原创文章。
在评估 eligibility 的 354 篇摘要中，仅有 6 项研究纳入定量综合分析，共涉及 301 例患者和 163 例对照。我们的分析显示，与对照组相比，患者的（）基因甲基化水平显著更高（标准化均数差[SMD]2.150，95%置信区间[CI]0.377，3.922；p = 0.017），尽管研究之间存在显著异质性（Q 值 = 239.90，p < 0.001；I² = 97.91%）。未发现明显的发表偏倚证据，尽管有一项研究敏感性足以使结果产生偏差，导致失去显著性（SMD 1.543，95%CI -0.300，3.387；p = 0.101）。在荟萃回归分析中，我们发现结果与年龄（p = 0.6519）和精子浓度（p = 0.2360）均无关。
精子DNA甲基化可能与辅助生殖技术（ART）中的表观遗传风险相关。（）基因可纳入前瞻性研究的基因panel中，旨在确定在接受ART的夫妇中进行分析的最具代表性和成本效益的基因。
