Centriole Regulation in Natural and Artificial Gametogenesis
DOI:
https://doi.org/10.65649/87tnc168Keywords:
Centriole, Gametogenesis, In Vitro Gametogenesis, Aneuploidy, Spindle Assembly, Developmental CompetenceAbstract
Centriole elimination is an evolutionarily conserved, essential process during gametogenesis that resets centrosome number to prevent aneuploidy in the zygote (Schatten & Sun, 2011). While in vitro gametogenesis (IVG) from pluripotent stem cells offers transformative potential for reproductive medicine, its fidelity in recapitulating key cytoplasmic organelle reprogramming events remains poorly characterized. This study presents a systematic comparative analysis of centriole elimination dynamics between natural mouse gametogenesis and leading IVG protocols. Employing high-resolution imaging, molecular profiling, and functional embryogenesis assays, we demonstrate that IVG-derived gametes exhibit profound defects. Centriole elimination in vitro is asynchronous, frequently incomplete, and driven by a dysregulated molecular cascade, leading to the persistent retention of structurally aberrant centrioles (Clift & Schuh, 2013). These organelles act as ectopic microtubule-organizing centers, causing multipolar spindle formation during meiosis and the first embryonic division. Consequently, embryos from IVG gametes with centriole retention suffer catastrophic failure, characterized by severe chromosome segregation errors and preimplantation arrest (Hendriks, Dancet, van Pelt, Hamer, & Repping, 2015). Our findings establish centriole elimination fidelity as a critical, previously overlooked benchmark for IVG. They reveal that the artificial microenvironment fails to provide the precise niche signaling required for this stringent developmental program, highlighting a major safety consideration and providing a mechanistic roadmap for refining synthetic gametogenesis protocols.
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