{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:35:58Z","timestamp":1760060158508,"version":"build-2065373602"},"reference-count":54,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background\/Objectives: Infertility, defined as the failure to achieve pregnancy after one year of regular unprotected intercourse, represents a significant global health challenge, with male factors contributing to approximately 50% of cases. In this epidemiological context, both primary male infertility (the inability to conceive a first child) and secondary male infertility (which occurs when a man who has already fathered a child faces difficulty conceiving again) remain poorly understood at the genetic level. This study explored the role of single-nucleotide polymorphisms (SNPs) in mitochondrial genes (MT-ND3, MT-ND4L, and MT-ND4) in primary and secondary male infertility. Methods: This study analyzed the genotype distributions of SNPs in 68 infertile males (49 with primary infertility and 19 with secondary infertility) using Sanger sequencing. Results: Key findings revealed that studied SNPs were significantly associated with infertility type. Specifically, rs2857285 (T&gt;C,G) in the ND4 gene showed a significant correlation (p = 0.023) with the TT genotype, which is prominent in primary infertility. Another SNP, rs28358279 (T&gt;A,C) in the ND4L gene, also demonstrated a significant correlation (p = 0.046) with the TT genotype, being more common in primary infertility. In addition, rs869096886 (A&gt;G) in the ND4 gene had a borderline correlation (p = 0.051), indicating a possible association between this SNP and reproductive duration. Conclusions: This study emphasizes the potential relevance of mitochondrial malfunction in male infertility, specifically the effects of studied SNPs on sperm survival and function over time. These findings suggest that certain mitochondrial SNPs might be potential biomarkers for infertility risk. Larger studies are needed to confirm these associations and examine the functional effects of these SNPs. Combining genetic analysis with environmental and lifestyle factors could enhance our understanding of male infertility and improve diagnostic and therapeutic strategies.<\/jats:p>","DOI":"10.3390\/medsci13030109","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T09:41:17Z","timestamp":1754300477000},"page":"109","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring Single-Nucleotide Polymorphisms in Primary and Secondary Male Infertility"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2673-2691","authenticated-orcid":false,"given":"Fatina W.","family":"Dahadhah","sequence":"first","affiliation":[{"name":"Department of Basic Dental Sciences, Faculty of Dentistry, The Hashemite University, Zarqa 13115, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6060-8283","authenticated-orcid":false,"given":"Mohanad","family":"Odeh","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmaceutical Sciences, The Hashemite University, Zarqa 13115, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4119-107X","authenticated-orcid":false,"given":"Heba A.","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Basic Dental Sciences, Faculty of Dentistry, The Hashemite University, Zarqa 13115, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9646-0746","authenticated-orcid":false,"given":"Jihad A. M.","family":"Alzyoud","sequence":"additional","affiliation":[{"name":"Department of Basic Dental Sciences, Faculty of Dentistry, The Hashemite University, Zarqa 13115, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manal Issam","family":"Abu Alarjah","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 21193, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1093\/humupd\/dmx021","article-title":"The diagnosis of male infertility: An analysis of the evidence to support the development of global WHO guidance\u2014Challenges and future research opportunities","volume":"23","author":"Barratt","year":"2017","journal-title":"Hum. Reprod. 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