(P-361) Eggs derived from cultured follicles in vitro generate embryos with altered ZGA gene expression

Abstract Authors: Edward J. Grow

Abstract Text: In vitro culture has enormous promise as a tractable experimental system to study follicle development and also as a translational approach to produce eggs for fertility treatments. Although well-established in the mouse system, most oocytes from in vitro follicle culture (IVFC) generate developmentally compromised embryos. To investigate the molecular mechanism underlying this phenotype, we have performed single-cell RNA-seq in oocytes from IVFC and resultant embryos. We find that a subset of oocytes in culture transcriptionally drift and precociously activate markers of ZGA. Additionally, we find that only ~50% of oocytes establish nuclear competency characterized by appropriate chromatin condensation. After egg activation, many embryos derived from IVFC oocytes arrest at the early ZGA stage and express high levels of early 2-cell stage transcripts such as Obox4. Importantly, these effects are not seen in oocytes developed in vivo and subjected to in vitro maturation. In summary our results show that IVFC might impart long-lasting potentially transgenerational effects on oocytes and embryos.