Sperm insulin-like growth factor 2 protein levels: implications for early embryo development

Research question: What is the role of sperm-derived insulin-like growth factor 2 (IGF2) protein in early embryo development, and what is its potential influence on outcomes in assisted reproductive technology (ART)? Design: In 27 infertile couples undergoing ART, IGF2 protein levels in spermatozoa were quantified using enzyme-linked immunosorbent assay. Their correlation with embryo morphokinetics was assessed via time-lapse imaging. The analysis was adjusted for female partner's age, body mass index and serum anti-M & uuml;llerian hormone levels. To explore underlying mechanisms, recombinant IGF2 was added to murine parthenote cultures. Transcriptome analysis was conducted at the blastocyst stage. Results: Sperm IGF2 levels were significantly associated with the number of post-gradient sperm recovered (r = 0.65; P < 0.001) and with the timing of pronuclear formation (r = -0.22; P = 0.04), even after adjusting for confounding factors, indicating a role in the earliest stages of embryogenesis. No significant correlation was observed with later stages of embryo development, possibly owing to a developmental transition from paternal to embryonic IGF2 transcript expression. Furthermore, IGF2 levels did not differ significantly among ART outcome groups (biochemical pregnancy, clinical pregnancy and live birth). Transcriptome analysis of IGF2-treated parthenotes revealed enrichment in pathways related to protein binding, which is critical for pronuclear formation. Conclusion: A potential involvement of sperm-delivered IGF2 in early post-fertilization events is suggested, with a limited apparent effect on later embryonic development or ART outcomes. Further investigation into the diagnostic and therapeutic relevance of IGF2 in the context of male-factor infertility is needed.