Tehran University of Medical Sciences Acta Biochimica Iranica 0001-5261 3 2 2025 06 25 62 72 Hajar Hajian Department of Clinical Biochemistry, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran Hamed Mirzaei Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran Zohreh Seyedi Department of Clinical Biochemistry, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran Mitra Motallebi Department of Microbiology, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran; E-mail: motallebi-m@kaums.ac.ir Mohamad Shahabodin Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran 2025 05 29 2025 08 05 Male infertility is a multifactorial condition, with an increasing body of evidence highlighting the pivotal role of seminal plasma biochemical markers and microbial infections in its pathogenesis and diagnosis. Seminal plasma, a complex fluid enriched with proteins, enzymes, antioxidants, and metabolites, reflects the functional status of the male reproductive tract. Alterations in its biochemical composition such as decreased antioxidant capacity, disrupted energy metabolism, and elevated inflammatory mediators, are frequently associated with impaired sperm function. Concurrently, microbial infections, including those caused by Chlamydia trachomatis and Escherichia coli, can adversely affect seminal parameters through direct sperm damage, oxidative stress, and inflammatory responses. Emerging evidence suggests intricate interactions between infections and biochemical milieu in seminal plasma, which may exacerbate sperm dysfunction and compromise fertility. This review synthesizes current knowledge on key seminal plasma biomarkers and their diagnostic utility, and elucidates the pathophysiological mechanisms linking microbial infections to male infertility. Understanding these interconnected pathways offers novel insights into male reproductive health and may facilitate the development of more targeted diagnostic and treatment strategies in the context of infertility. https://abi.tums.ac.ir/index.php/abi/article/view/124 https://abi.tums.ac.ir/index.php/abi/article/download/124/104