Losing the maternal effect gene Nlrp2 alters the ovulated mouse oocytes transcriptome and impacts histone demethylase KDM1B expression

Abstract The subcortical maternal complex (SCMC) is a multiprotein complex in oocytes and preimplantation embryos that is encoded by maternal effect genes. The SCMC is essential for zygote-to-embryo transition, early embryogenesis, and critical zygotic cellular processes like spindle positioning and symmetric division. Maternal deletion of Nlrp2, which encodes an SCMC protein, results in increased early embryonic loss and abnormal DNA methylation in embryos. We performed RNA sequencing on pools of oocytes that we isolated and collected from cumulus-oocyte complexes (COCs) after inducing ovarian stimulation in wild-type and Nlrp2-null female mice. Using a mouse reference genome-based analysis, we found 231 differentially expressed genes (DEGs) in Nlrp2-null compared to WT oocytes (123 up- and 108 downregulated; adjusted p < 0.05). The DEGs we identified were enriched for processes involved in neurogenesis, gland morphogenesis, and protein metabolism and for post-translationally methylated proteins. When we compared our RNA sequencing results to an oocyte-specific reference transcriptome that contains many previously unannotated transcripts, we found 228 DEGs, including genes not identified with the first analysis. Intriguingly, 68% and 56% of DEGs from the first and second analyses, respectively, overlap with oocyte-specific hyper- and hypomethylated domains. Thus, the differentially expressed transcripts in the oocytes of mice lacking NLRP2 are enriched for genes that overlap with oocyte-specific methylated domains. This is consistent with the known functional link between transcription and methylation in oocytes.