Developmental block in ruminant embryos: Mechanisms, molecular insights and potential interventions.

Developmental block remains one of the major hurdles that makes it hard to develop embryos in vitro more efficiently. In ruminants, it is predominantly observed during the 8-16 cell stage, coinciding with the maternal-to-zygotic transition (MZT) and embryonic genome activation (EGA). In addition, reducing maternal transcripts and initiating embryonic transcription correctly is a major reason for developmental arrest. A broad array of molecular mechanisms has been implicated, encompassing incomplete epigenetic regulation, mitochondrial dysfunction, oxidative stress, improper cell cycle progression, and dysregulated apoptosis. During this process, several key genes, including ZAR1, NPM2, DPPA3, DNMTs, Cyclin B1, BCL2, and antioxidant enzymes (SOD1, GPX1, and CAT) have been recognized as essential regulators of the block. External factors, especially poor in vitro culture conditions, high oxygen levels, and the secretion of harmful metabolites, make developmental failure even worse. Recent research has underscored the significance of antioxidant supplementation, epigenetic modulators, and enhanced culture systems in mitigating developmental barriers. Therefore, the current review summarises the contemporary insights into the factors and molecular mechanisms responsible for ruminant embryonic developmental block, focusing on MZT, oxidative stress, and epigenetic regulation. It also addresses potential strategies to enhance the developmental competence of ruminant embryos in vitro.