Unraveling the human Y chromosome in male health: structural abnormalities and microdeletions with emerging clinical implications

Abstract The human Y chromosome has traditionally been viewed as a gene-poor chromosome, primarily relevant to male reproductive health. However, recent evidence challenges this narrow perspective. This narrative review explores the Y chromosome’s unique structure, evolution, and functional relevance, with a particular focus on the azoospermia factor (AZF) regions and their associated genes. We examine how microdeletions in these regions, along with Y chromosome abnormalities, contribute to male infertility and discuss the underlying genetic mechanisms. Beyond reproduction, emerging evidence connects Y-linked variation and loss of Y (LOY) to cardiometabolic disorders and cancer. In addition, we highlight the importance of current diagnostic techniques used to detect Y chromosome abnormalities, including molecular and cytogenetic methods for infertility diagnosis. Understanding the Y chromosome’s genetic landscape is essential not only for accurate diagnosis but also for advancing precision medicine, forensic genetics, and potential gene-based interventions.