Background and Aim: The human methylenetetrahydrofolate reductase (MTHFR)
gene plays a crucial role in folate metabolism. Data regarding the influence of
MTHFR gene polymorphisms on male fertility status are conflicting. The present
study aimed to investigate the possible role of genetic variants of the MTHFR 677
C→T and 1298 A→C and the seminal plasma levels of S-adenosylmethionine (SAM),
S-adenosylhomocysteine (SAH) in male infertility. Patients & Methods: The present
study included 229 men attending the Andrology Outpatient Clinic, Mansoura
University Hospital. The semen samples obtained from men were grouped according
to the profile of seminogram into normozoospermic (N), oligoathenoteratozoospermia
(OAT) and azoospermia (AZ). Spermatozoa were separated and the purified
spermatozoa were used for assessment of acrosine activity by gelatinolysis. High
Performance Liquid Chromatography equipped with a reversed-phase column-C18,
and UV detector at 254 nm was used to separate SAM and SAH. Genomic DNA was
isolated 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 the
current study showed that SAM, SAM/SAH ratio and acrosine activity index to be
significantly decreased in OAT and AZ compared with normozoospermia. MTHR
1298AA and 677CC genotypes frequency was significantly higher in OAT and AZ
groups when compared to N group..Also, SAH were significantly increased in MTHR
1298AA and 677CC genotypes. Conclusion: The polymorphisms in the MTHR
A1298C and C677T gene were associated with abnormal sperm function, morphology
and motility. Carrier of 1298AA and 677CC genotypes had higher level of SAH. It
could be concluded that methionine metabolism is abnormal in infertile men denoted
by impaired SAM and SAH levels. Further studies may be of benefit for new strategies
in therapy for male infertility.