Testis development and fertility potential in Klinefelter syndrome

Klinefelter syndrome is the most prevalent chromosome disorder in infertile men, characterized by one or more additional X chromosomes. This manuscript reviews the spectrum of phenotypic variability, testicular histopathology and hormonal imbalances associated with Klinefelter syndrome across different developmental stages from infancy through adulthood. Klinefelter syndrome typically manifests with small firm testes, azoospermia, hypergonadotrophic hypogonadism and a tall feminine stature. Testicular biopsies reveal progressive germ cell depletion, seminiferous tubule hyalinization, testicular fibrosis and Leydig cell hyperplasia, contributing to elevated luteinizing hormone and follicle stimulating hormone levels alongside decreased inhibin B and anti-Müllerian hormone levels from mid-puberty onwards. Despite extensive research, the exact mechanisms underlying these changes remain unclear, highlighting the need for further investigation to enhance diagnostic accuracy and therapeutic outcomes for Klinefelter individuals, especially in fertility preservation and restoration strategies.