Enzymatic and genetic evaluation of butyrylcholinesterase in male infertility

OBJECTIVE: To investigate the potential role of butyrylcholinesterase (BChE) enzyme activity and tentative association of BCHE gene single nucleotide polymorphisms (rs3495, rs1803274) with risk of male infertility. Male infertility is a highly prevalent multifactorial condition with complex heterogeneous phenotypic spectrum. A significant global variation has been observed in the prevalence of male infertility contributing to approximately 20%-70% of overall infertility. An interplay of genetic, hormonal, environmental, and lifestyle factors are involved in the development of male infertility. Butyrylcholinesterase, an enzyme involved in oxidative stress and sperm function may play a role in infertility, but its genetic and enzymatic profiles in male infertility are unexplored. DESIGN: A case-control/observational study was conducted enrolling 55 fertile and infertile male individuals. SUBJECTS: A total of 55 fertile and infertile male volunteers were included in the study. EXPOSURE: Volunteers were clinically diagnosed for infertility. MAIN OUTCOME MEASURES: Plasma BChE activity was estimated spectrophotometrically by Ellman's method. The single nucleotide polymorphism genotyping of BCHE gene variants was performed by polymerase chain reaction-restriction fragment length polymorphism and tetra-primer amplification refractory mutation system-polymerase chain reaction. RESULTS: The infertile group exhibited significantly lower BChE activity compared with the fertile group. In addition, a notable genetic association of BCHE variants with the risk of male infertility was identified. The BCHE rs3495 showed significant correlation in the dominant model (odds ratio = 21.67) and allelic distribution (odds ratio = 3.30), whereas rs1803274 showed robust association in all models. CONCLUSION: This is the first study linking BCHE variants and reduced BChE enzymatic activity with male infertility. These findings suggest BChE as a potential biomarker and therapeutic target for idiopathic infertility.