Male infertility is a multifactorial disorder frequently associated with compromised spermatogenic function and aberrant semen parameters, with underlying causes localized to pre-testicular (endocrine), testicular, or post-testicular levels. Disruptions in regulatory pathways across these levels can ultimately impair male reproductive capacity. Given the male gamete’s contribution of half the embryonic genome, the integrity of the paternal genetic landscape is critical for successful fertilization and embryo development. Traditional investigations have elucidated numerous genetic causes, including chromosomal anomalies such as Klinefelter syndrome and structural rearrangements, as well as Y chromosome microdeletions, particularly in the azoospermia factor regions, which account for a significant proportion of non-obstructive azoospermia. Mutations in autosomal genes including CFTR, AR, SYCP3, PLK4, and INSL3 have been implicated in obstructive azoospermia, meiotic arrest, and testicular descent disorders. While gene polymorphisms in DAZL, TP53, and various metalloproteinases continue to be investigated for their potential role in modulating spermatogenic efficiency and reproductive outcomes, these findings remain subject to further validation. In addition to genetic factors, epigenetic mechanisms have gained increasing attention as key regulators of male fertility. Changes in DNA methylation, histone modifications, and the organization of chromatin within sperm cells can regulate gene activity without changing the genetic code. Such epigenetic modifications have been linked to disrupted sperm production and reduced embryo quality. Incorporating epigenetic profiling into the clinical evaluation of male infertility holds promise for improving diagnostic accuracy and advancing personalized reproductive care. This thesis aims to present and critically analyze the genetic and epigenetic causes of male infertility, emphasizing their relevance in contemporary diagnostic and therapeutic strategies.
Νίκη Κ. Κατσάκογλου (Wed,) studied this question.