Mutations in the Methylenetetrahydrofolate Reductase Gene and Methionine Metabolism in male infertility

Abstract

Background and Aim: The human methylenetetrahydrofolate reductase (MTHFR)gene plays a crucial role in folate metabolism. Data regarding the influence ofMTHFR gene polymorphisms on male fertility status are conflicting. The presentstudy aimed to investigate the possible role of genetic variants of the MTHFR 677C→T and 1298 A→C and the seminal plasma levels of S-adenosylmethionine (SAM),S-adenosylhomocysteine (SAH) in male infertility. Patients & Methods: The presentstudy included 229 men attending the Andrology Outpatient Clinic, MansouraUniversity Hospital. The semen samples obtained from men were grouped accordingto the profile of seminogram into normozoospermic (N), oligoathenoteratozoospermia(OAT) and azoospermia (AZ). Spermatozoa were separated and the purifiedspermatozoa were used for assessment of acrosine activity by gelatinolysis. HighPerformance Liquid Chromatography equipped with a reversed-phase column-C18,and UV detector at 254 nm was used to separate SAM and SAH. Genomic DNA wasisolated from peripheral blood leukocytes by Genta genomic DNA purification kit.MTHFR 677 C→T and 1298 A→C polymorphisms were analyzed using PCR,restriction enzymes and agarose gel electrophoresis. Results: The results of thecurrent study showed that SAM, SAM/SAH ratio and acrosine activity index to besignificantly decreased in OAT and AZ compared with normozoospermia. MTHR1298AA and 677CC genotypes frequency was significantly higher in OAT and AZgroups when compared to N group..Also, SAH were significantly increased in MTHR1298AA and 677CC genotypes. Conclusion: The polymorphisms in the MTHRA1298C and C677T gene were associated with abnormal sperm function, morphologyand motility. Carrier of 1298AA and 677CC genotypes had higher level of SAH. Itcould be concluded that methionine metabolism is abnormal in infertile men denotedby impaired SAM and SAH levels. Further studies may be of benefit for new strategiesin therapy for male infertility.