Association of MTHFD1G1958A, MTHFD1T401C, and DHFR-19bp variants with sperm criteria and unexplained male infertility: a case–control study on Algerian population
Abstract Background Methylenetetrahydrofolate dehydrogenase (MTHFD1) and Dihydrofolate reductase (DHFR) are pivotal enzymes in the folate metabolic pathway, playing essential roles in DNA synthesis, repair, and methylation processes critical for spermatogenesis. Numerous studies have implicated gene...
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SpringerOpen
2025-04-01
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| Series: | Middle East Fertility Society Journal |
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| Online Access: | https://doi.org/10.1186/s43043-025-00223-y |
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| author | Nour El Houda Bousnane Abed Alkarem Abu Alhaija Housna Labed Anissa Fizazi Chahinez Amira Dahmani May Fouad Sadiq |
| author_facet | Nour El Houda Bousnane Abed Alkarem Abu Alhaija Housna Labed Anissa Fizazi Chahinez Amira Dahmani May Fouad Sadiq |
| author_sort | Nour El Houda Bousnane |
| collection | DOAJ |
| description | Abstract Background Methylenetetrahydrofolate dehydrogenase (MTHFD1) and Dihydrofolate reductase (DHFR) are pivotal enzymes in the folate metabolic pathway, playing essential roles in DNA synthesis, repair, and methylation processes critical for spermatogenesis. Numerous studies have implicated genetic variations in their encoding genes in the susceptibility to diverse diseases, including reproductive disorders. Objective The aim of our study is to investigate the potential association between MTHFD1G1958A, MTHFD1T401C, and DHFR-19bp polymorphisms, sperm parameters, and the risk of idiopathic male infertility. Methods We conducted a case–control study involving 104 infertile men and 104 controls. Genomic DNA was extracted from blood samples using a commercially kit, and molecular analyses were carried out through direct PCR and PCR–RFLP. Results Statistical analysis showed significant associations of MTHFD1G1958A and MTHFD1T401C mutant genotypes with male infertility (P < 0.05). The MTHFD1958AA polymorphism was linked to reduced sperm mobility, vitality, and normal morphology (P = 0.001, P = 0.048, P ≤ 0.0001, respectively). MTHFD1T401C was significantly associated with vital sperm (P = 0.009). No significant association was found for the DHFR-19bp polymorphism. Conclusion This study suggests that MTHFD1G1958A and MTHFD1T401C polymorphisms may contribute to unexplained male infertility, with the MTHFD1 1958GA linked to defects sperm parameters. |
| format | Article |
| id | doaj-art-cfac4f66ef4e410d82f9e09d2b7e0dbe |
| institution | DOAJ |
| issn | 2090-3251 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Middle East Fertility Society Journal |
| spelling | doaj-art-cfac4f66ef4e410d82f9e09d2b7e0dbe2025-08-20T03:18:34ZengSpringerOpenMiddle East Fertility Society Journal2090-32512025-04-0130111110.1186/s43043-025-00223-yAssociation of MTHFD1G1958A, MTHFD1T401C, and DHFR-19bp variants with sperm criteria and unexplained male infertility: a case–control study on Algerian populationNour El Houda Bousnane0Abed Alkarem Abu Alhaija1Housna Labed2Anissa Fizazi3Chahinez Amira Dahmani4May Fouad Sadiq5Department of Biology, Faculty of Natural and Life Sciences, University of OranDivision of Oral Bioscience, Dublin Dental University Hospital, and University of Dublin, Trinity College DublinLaboratory of Acquired and Constitutional Genetic Diseases, Faculty of Medicine, University of Batna 2Department of Biology, Faculty of Natural and Life Sciences, University of OranDepartment of Biology, Faculty of Natural and Life Sciences, University Of MostaganemDepartment of Biological Sciences, Faculty of Sciences, Yarmouk UniversityAbstract Background Methylenetetrahydrofolate dehydrogenase (MTHFD1) and Dihydrofolate reductase (DHFR) are pivotal enzymes in the folate metabolic pathway, playing essential roles in DNA synthesis, repair, and methylation processes critical for spermatogenesis. Numerous studies have implicated genetic variations in their encoding genes in the susceptibility to diverse diseases, including reproductive disorders. Objective The aim of our study is to investigate the potential association between MTHFD1G1958A, MTHFD1T401C, and DHFR-19bp polymorphisms, sperm parameters, and the risk of idiopathic male infertility. Methods We conducted a case–control study involving 104 infertile men and 104 controls. Genomic DNA was extracted from blood samples using a commercially kit, and molecular analyses were carried out through direct PCR and PCR–RFLP. Results Statistical analysis showed significant associations of MTHFD1G1958A and MTHFD1T401C mutant genotypes with male infertility (P < 0.05). The MTHFD1958AA polymorphism was linked to reduced sperm mobility, vitality, and normal morphology (P = 0.001, P = 0.048, P ≤ 0.0001, respectively). MTHFD1T401C was significantly associated with vital sperm (P = 0.009). No significant association was found for the DHFR-19bp polymorphism. Conclusion This study suggests that MTHFD1G1958A and MTHFD1T401C polymorphisms may contribute to unexplained male infertility, with the MTHFD1 1958GA linked to defects sperm parameters.https://doi.org/10.1186/s43043-025-00223-yMale infertilityMTHFD1C401TMTHFD1G1958ADHFR-19bpSemen criteriaFolate metabolism |
| spellingShingle | Nour El Houda Bousnane Abed Alkarem Abu Alhaija Housna Labed Anissa Fizazi Chahinez Amira Dahmani May Fouad Sadiq Association of MTHFD1G1958A, MTHFD1T401C, and DHFR-19bp variants with sperm criteria and unexplained male infertility: a case–control study on Algerian population Middle East Fertility Society Journal Male infertility MTHFD1C401T MTHFD1G1958A DHFR-19bp Semen criteria Folate metabolism |
| title | Association of MTHFD1G1958A, MTHFD1T401C, and DHFR-19bp variants with sperm criteria and unexplained male infertility: a case–control study on Algerian population |
| title_full | Association of MTHFD1G1958A, MTHFD1T401C, and DHFR-19bp variants with sperm criteria and unexplained male infertility: a case–control study on Algerian population |
| title_fullStr | Association of MTHFD1G1958A, MTHFD1T401C, and DHFR-19bp variants with sperm criteria and unexplained male infertility: a case–control study on Algerian population |
| title_full_unstemmed | Association of MTHFD1G1958A, MTHFD1T401C, and DHFR-19bp variants with sperm criteria and unexplained male infertility: a case–control study on Algerian population |
| title_short | Association of MTHFD1G1958A, MTHFD1T401C, and DHFR-19bp variants with sperm criteria and unexplained male infertility: a case–control study on Algerian population |
| title_sort | association of mthfd1g1958a mthfd1t401c and dhfr 19bp variants with sperm criteria and unexplained male infertility a case control study on algerian population |
| topic | Male infertility MTHFD1C401T MTHFD1G1958A DHFR-19bp Semen criteria Folate metabolism |
| url | https://doi.org/10.1186/s43043-025-00223-y |
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