Inhibition of BLM helicase disrupts organelle function and oocyte maturation in goats

During the first meiotic division, oocytes inevitably undergo physiological DNA double-strand breaks (DSBs), which are primarily repaired through BLM helicase-mediated homologous recombination repair (HRR). This study investigated the consequences of BLM helicase suppression on meiotic maturation in goat oocytes, revealing that BLM helicase exhibited nuclear-predominant expression over cytoplasmic localization during MI/MII stages and colocalized with spindle fibers. Functional impairment of BLM helicase blocked oocyte maturation, accompanied by dysregulated expression of cumulus expansion-related genes, downregulation of oocyte paracrine factors, elevated ROS accumulation, compromised mitochondrial function, upregulated endoplasmic reticulum (ER) stress-responsive genes, impaired autophagolysosomal activity, and disrupted Golgi distribution and ribosome function, though mitochondrial fusion and fission remained unaffected. Transcriptomics and RT-qPCR analysis further demonstrated that the inhibition of BLM significantly downregulated expression of HRR-associated genes (REC8, PPP4C) while upregulating NHEJ-associated genes (DCLRE1B, ERCC4), suggesting that BLM helicase deficiency shifts DSB repair from HRR to error-prone NHEJ. Consistently, immunofluorescence (IF) staining revealed a significant increase in the DNA damage response factor p-ATM and the repair protein RAD51, indicating that BLM inhibition induces substantial DNA damage in oocytes. These results demonstrate that BLM plays a critical role in maintaining nuclear genomic stability in oocytes. Thereby, this study highlights BLM helicase as a critical regulator of organelle homeostasis during meiotic progression and provides novel mechanistic insights into its multifaceted roles in oocyte maturation.