Association between AZF microdeletions and polymorphisms in the MTHFR, MTR, and MTRR genes in men with severe oligozoospermia and non-obstructive azoospermia
- VernacularTitle:Хүнд хэлбэрийн олигозоосперми, бөглөрөлт бус азооспермитэй эрэгтэйчүүдэд Y хромосомын AZF микроделеци болон MTHFR, MTR, MTRR генүүдийн полиморфизмуудыг тодорхойлсон дүн
- Author:
Ariunzaya A
1
;
2
;
Khosbayar T
3
;
Buyankhuu T
1
Author Information
1. Department of Biochemistry, School of Biomedicine, MNUMS
2. Clinical Molecular Diagnostic Center, MNUMS
3. Department of Clinical Laboratory, School of Medicine, MNUMS
- Publication Type:Journal Article
- Keywords:
Infertility, Folic acid, 5-MTHF
- From:
Mongolian Journal of Health Sciences
2025;89(5):100-104
- CountryMongolia
- Language:Mongolian
-
Abstract:
Background:Approximately 30–50% of cases of severe oligozoospermia and non-obstructive azoospermia are attributed
to genetic factors, as determined through semen analysis. Microdeletions in the AZF (Azoospermic Factor) region of
the Y chromosome represent one of the genetic causes of male infertility. The European Academy of Andrology (EAA)
recommends screening for AZF microdeletions in men diagnosed with azoospermia or severe oligozoospermia. Folate
metabolism plays a crucial role in spermatogenesis and germ cell development. Polymorphisms in genes involved in this
metabolic pathway such as MTHFR, MTR, and MTRR have been implicated in the pathogenesis of oligozoospermia and
azoospermia. The reason for conducting this research was lack of studies investigating the in Mongolia have concurrently
investigated the association between AZF microdeletions on the Y chromosome and the presence of MTHFR 677C>T and
1298A>C, MTR 2756A>G, and MTRR 66A>G polymorphisms in men with severe oligozoospermia or non-obstructive
azoospermia.
Aim:To determine the presence of Y chromosome AZF microdeletions, as well as the MTHFR 677C>T and 1298A>C,
MTR 2756A>G, and MTRR 66A>G polymorphisms in men with severe oligozoospermia and non-obstructive azoospermia
Materials and Methods:This study was conducted at the Clinical Molecular Diagnostics Center of the Mongolian National
University of Medical Sciences (MNUMS). Peripheral blood samples were collected from all study participants,
and genomic DNA was extracted using the “PROBA-RAPID Genetika” DNA extraction kit manufactured by DNA-Technology
LLC (Russian Federation). Thirteen AZF microdeletions (sY84, sY86, sY127, sY134, sY142, sY242, sY254, sY255,
sY615, sY1125, sY1197, sY1206, sY1291) were detected using the “AZF Microdeletions REAL-TIME PCR Genotyping
Kit.” Polymorphisms in the MTHFR gene (677C>T and 1298A>C), the MTR gene (2756A>G), and the MTRR gene
(66A>G) were identified using the “Folate Metabolism REAL-TIME PCR Genotyping Kit.”
Results:A total of 11 men aged between 18 and 44 years who had been diagnosed with severe oligozoospermia or
non-obstructive azoospermia based on repeated semen analyses (two or more times) were included in this study. Among
participants with severe oligozoospermia or non-obstructive azoospermia, AZF microdeletion analysis of the Y chromosome
revealed one case with an sY1291 (AZFc) microdeletion and another case with an sY1197 (AZFc) microdeletion.
No AZF microdeletions were detected in the remaining participants. Regarding the MTHFR 677C>T polymorphism,
the homozygous wild-type CC genotype was observed in 55% (6), the heterozygous CT genotype in 18% (2), and the
homozygous mutant TT genotype in 27% (3). The frequency of the C allele was 64% (14), while the risk-associated T
allele was 36% (8). For the MTHFR 1298A>C polymorphism, the homozygous AA genotype was found in 64% (7), the
heterozygous AC genotype in 27% (3), and the homozygous CC genotype in 9% (1). The A allele frequency was 81%
(17), and the risk-associated C allele frequency was 19% (4). In the case of the MTR 2756A>G polymorphism, 64% (7)
of participants had the AA genotype, and 36% (4) had the AG genotype. The GG genotype was not detected. The A allele
frequency was 82% (18), and the risk-associated G allele frequency was 18% (4). For the MTRR A66G polymorphism,
the AA genotype was observed in 36% (4), and the AG genotype in 64% (7). The GG genotype was not detected. The A
allele frequency was 68% (15), and the risk-associated G allele frequency was 32% (7).
Conclusion:In this study, Y chromosome AZF microdeletions were detected in 18% of participants with severe oligozoospermia
or non-obstructive azoospermia, which is considered relatively low. In such cases, identifying polymorphisms
in the MTHFR, MTR, and MTRR genes becomes important. Disruptions in folate metabolism caused by these polymorphisms
can lead to elevated homocysteine levels. Supplementation with activated folate (5-MTHF) has been shown to
help maintain normal plasma homocysteine concentrations, which may be beneficial in individuals with impaired folate
metabolism.
- Full text:2025121011530994336Хүнд хэлбэрийн олигозоосперми, бөглөрөлт бус азооспермитэй эрэгтэйчүүдэд Y хромосомын.pdf
