Human IGF2 mRNA

Spermatozoa have been shown to carry key RNAs that, based on animal evidence, appear to play a role in early embryonic development. In this context, a potential key growth regulator is insulin-like growth factor 2 (IGF2), a highly conserved paternally expressed imprinted gene involved in cell growth and proliferation. Recent observations suggest that it is also expressed in human sperm. Here, researchers analyzed the transcriptome of blastocysts obtained after injection of Igf2 mRNA in mouse parthenogenetics. Sperm IGF2 mRNA was negatively correlated with the time to the 2-cell stage (t2), t3, t4, t5, and blastocyst expansion (tEB), and was independent of maternal age, body mass index, anti-mullerian hormone levels, and oocyte quality. In the animal study, transcriptome analysis revealed that 65 and 36 genes were upregulated and downregulated, respectively, in the experimental group compared to the control group. These genes belong to pathways regulating early embryonic development, thus supporting findings found in humans. This study has the potential to challenge the long-held view that sperm are simply vehicles for carrying paternal DNA. Instead, it suggests that IGF2 mRNA in healthy sperm provides critical support for early embryonic development.

A total of 65 genes were found to be upregulated and 36 genes were downregulated in parthenogenetic cells injected with Igf2 mRNA compared with the control group (Figure 1).

Figure 1. Heatmap showing differently expressed genes in parthenotes injected with Igf2 mRNA (n = 45) compared to controls (n = 45). (Cannarella R, et al., 2024)