SAT-174 IGF2 Protein Levels in Spermatozoa: Implications For Early Embryo Development

Abstract Disclosure: R. Cannarella: None. O.J. Rando: None. S. Chamayou: None. S. La Vignera: None. A.E. Calogero: None. Background. Insulin-like growth factor 2 (IGF2) is a paternally expressed imprinted gene that plays a critical in embryo growth and development. Our recent research demonstrated that sperm-derived IGF2 mRNA levels influence early human embryo development, particularly from day 2 post-fertilization, when the transcript is translated into protein. From day 3 onward, embryo growth is primarily driven by the transcriptional activity of the gene within the embryo itself. Hypothesis. In this study, we hypothesized that IGF2 protein carried by spermatozoa into the oocyte affects early post-fertilization processes on day 1, prior to translation of the sperm-delivered transcript and before zygote genome activation occurs. Methods. To test this hypothesis, we measured sperm IGF2 protein levels in the same semen samples used for homologous assisted reproductive technology (ART) in infertile couples, whose embryo morphokinetics were assessed using time-lapse technology. We then analyzed the correlation between sperm IGF2 protein levels and embryo morphokinetic parameters, adjusting for potential confounding factors. Additionally, we examined the clinical relevance of sperm-carried IGF2 protein by assessing its relationship with sperm quality and ART outcomes. Finally, to explore potential mechanistic explanations for our findings, we analyzed the transcriptome of blastocysts derived from mouse parthenotes incubated with IGF2 protein. Results. Our results revelaed a significant correlation between sperm IGF2 protein levels and pronuclei formation (tPNappear), suggesting a potential role in facilitating initial stages of embryogenesis. However, no significant associations were found with later stages of embryo development, likely due to the transition from sperm-derived IGF2 protein to embryo-derived IGF2 transcripts or the initiation of IGF2 gene transcription in the embryo. Additionally, IGF2 protein levels did not significantly differ across ART outcome groups, including biochemical pregnancy, clinical pregnancy, and live birth. Transcriptome analysis of parthenotes incubated with recombinant murine IGF2 showed enrichment in pathways related to protein binding and microtubule dynamics, both of which are essential for pronuclei formation. Conclusion. These findings highlight the role of sperm-delivered IGF2 protein in early post-fertilization events, with limited influence on later embryo development or ART success rates. This study highlights the importance of sperm-carried IGF2 protein in early human embryogenesis and provides a foundation for future research into its diagnostic and therapeutic potential in male infertility. Presentation: Saturday, July 12, 2025