Unraveling the metabolic and autoimmune links to male infertility: a narrative review

Nicholas W. Shely¹, Jacob M. Parker¹, Hayden J. Oyler¹, Alexander C. Lien¹, Bode T. Eisenmenger², Mark R. Wakefield^2,3, Yujiang Fang^1,2,3,*
1 Department of Microbiology, Immunology & Pathology, Des Moines University College of Osteopathic Medicine, West Des Moines, IA, USA
2 Department of Surgery, University of Missouri School of Medicine, Columbia, MO, USA
3 Ellis Fischel Cancer Center, University of Missouri School of Medicine, Columbia, MO, USA
* Corresponding Author: Yujiang Fang. Email: email
(This article belongs to the Special Issue: Advances and Challenges In Male Infertility: From Molecular Mechanisms to Clinical Applications)

Canadian Journal of Urology https://doi.org/10.32604/cju.2026.078502

Received 01 January 2026; Accepted 25 May 2026; Published online 29 June 2026

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Abstract

Male infertility (MI) is a common condition traditionally viewed as a strictly reproductive issue; however, increasing evidence suggests that MI may reflect a broader health issue. Associations of MI and metabolic syndrome (MetS), as well as autoimmune diseases, have been observed. This review summarizes the current evidence linking MI with these conditions, detailing how chronic oxidative stress, systemic proinflammatory cytokines and blood-testis barrier disruption serve as drivers of reproductive decline. Specifically, MetS impairs male fertility through central hypothalamic-pituitary-gonadal (HPG) axis dysregulation, oxidative stress, insulin resistance, and testicular hyperthermia. Autoimmune diseases, including rheumatoid arthritis, psoriasis, and systemic lupus erythematosus (SLE), impair male fertility through chronic inflammation, oxidative stress, and peripheral hormonal dysregulation. Emerging evidence also suggests a bidirectional relationship, implying that MI can precede or exacerbate systemic illness. MI as an indicator of overall health may improve early detection of metabolic and autoimmune disorders, allowing for a more holistic management.