The Identification of Genetic Factors Contributing to Human Oocytes Maturation Arrest Using Whole-Genome Sequencing

Female fertility is dependent on the successful maturation of oocytes, a complex and meticulously regulated cellular process that prepares oocytes for fertilization and subsequent embryonic development. However, with advancing age and the onset of reproductive senescence, the probability of errors in this process increases significantly. These age-related alterations are associated with the accumulation of genetic and epigenetic abnormalities, mitochondrial dysfunction, and modifications in cytoskeletal function, all of which elevate the risk of oocyte maturation defects, embryonic developmental anomalies, and infertility. In this study, we conducted a genetic analysis of a patient experiencing female infertility due to oocyte maturation arrest and identified a heterozygous variant, c.527C>T (p.Ser176Leu), in the TUBB8 gene. This variant disrupts microtubule formation, leading to defects in meiotic spindle formation and subsequent oocyte arrest. Variants in the TUBB8 gene, which encodes a crucial component of microtubules, have been implicated in the pathogenesis of oocyte maturation arrest, abnormal fertilization, and other related disorders. Such changes may be particularly pronounced in women exhibiting characteristics of reproductive senescence.