Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan.
Institute of Medical Research and Medical Plants Studies, Yaounde, Cameroon.
PLoS One. 2023 Apr 7;18(4):e0282579. doi: 10.1371/journal.pone.0282579. eCollection 2023.
Male infertility is a complex and polygenic reproductive disease. 10-15% of the males are affected by idiopathic infertility conditions. Acetylcholine (ACh), a major neurotransmitter has been reported to play a non-neuronal role as well. Acetylcholinesterase (AChE) is the primary ACh hydrolyzing enzyme whose over or lower expression influence the availability of ACh for physiological roles. The purpose of the study was to find the possible impact and association of acetylcholinesterase, ACHE gene variant rs 17228602, and pro-inflammatory cytokines in clinically diagnosed infertile males. The study includes clinically diagnosed fifty non-infertile (control) and forty-five infertile males. Whole blood AChE enzymatic activity was measured. Genotyping of rs17228602 was carried out from peripheral blood by standard molecular methods. Pro-inflammatory cytokines were determined by the ELISA method. AChE enzyme was found to be significantly elevated in infertile than non-infertile males. ACHE SNP rs17228602 had shown significant association in dominant model (odd ratio = 0.378, 95% CI = 0.157-0.911, p-value 0.046). Pro-inflammatory cytokine IL-1β was notably increased with statistical significance (p ≤0.05) in male infertile patients. The study concludes and speculates that AChE plays role in the pathogenesis of male infertility through the modulation of inflammatory pathways. Further studies in this direction may resolve the idiopathic cases of male infertility. Other variants of ACHE and the association of miRNA for the regulation of AChE in male infertility are suggested for further insight.
男性不育是一种复杂的多基因生殖疾病。10-15%的男性受到特发性不育症的影响。乙酰胆碱(ACh),一种主要的神经递质,据报道也具有非神经元作用。乙酰胆碱酯酶(AChE)是主要的 ACh 水解酶,其过度或低表达会影响 ACh 发挥生理作用的可用性。本研究旨在探讨乙酰胆碱酯酶、ACHE 基因变异 rs17228602 和促炎细胞因子在临床诊断为不育的男性中的可能影响和相关性。该研究包括 50 名临床诊断为非不育(对照)和 45 名不育男性。测定全血 AChE 酶活性。通过标准分子方法从外周血中对 rs17228602 进行基因分型。通过 ELISA 法测定促炎细胞因子。发现不育男性的 AChE 酶活性明显高于非不育男性。ACHE SNP rs17228602 在显性模型中显示出显著相关性(优势比=0.378,95%置信区间=0.157-0.911,p 值=0.046)。促炎细胞因子 IL-1β 在男性不育患者中显著增加,具有统计学意义(p≤0.05)。研究得出结论并推测,AChE 通过调节炎症途径在男性不育的发病机制中发挥作用。进一步的研究可能会解决男性特发性不育症的问题。建议进一步研究 ACHE 的其他变体和 miRNA 对男性不育中 AChE 的调节作用,以获得更深入的了解。