Physical exercise before pregnancy helps the development of mouse embryos produced in vitro

- Pre-gestational exercise enhances the formation of blastocyst produced in vitro.
- Pre-gestational exercise improves metabolism in embryos produced in vitro.
- Pre-gestational exercise normalizes epigenetic modifications in embryos.

Effects of pre-gestational physical activity on the later development of embryos generated in vitro were evaluated. Kunming mice were divided into two groups, namely exercised and unexercised, with the former undergoing physical training on a motor-driven leveled treadmill over a period of 4 weeks (5 days/week and 60 min/day). After that, following superovulation, collection of oocytes from both groups was performed for in vitro fertilization (IVF) and somatic cell nuclear transfer (SCNT). Notably and specifically, natural mating between the unexercised mice was also done for in vivo fertilization (IVIF). Observation on the preimplantation embryo development showed that SCNT embryos from exercised group (NEM) had significant higher rates of cleavage and formation of blastocyst containing more blastomeres compared to SCNT embryos from unexercised group (NCM); while IVF embryos in exercised group (FEM) showed a significant higher rate of cleavage and blastocyst formation. Further analysis of embryos from the trained group on the molecular level demonstrated a prominent increase in terms of ATP levels, mitochondria membrane potential (Δψm) and mtDNA copy number and an obvious decrease in H2O2 concentration than those from the respective control group. Meanwhile, epigenetically, methylation levels of CpG sites on imprinting control regions of imprinted genes (Igf2, Igf2r, Meg 3 and H19) in the NEM embryos were normalized in exercise groups compared to the NCM embryos, which were comparable to the in vivo-derived embryos. Moreover, global DNA and histone methylation (H3K4m2, H3K9m3 and H3K36m) further confirmed that NEM-derived embryos and in vivo-derived ones stay in the same cluster, indicating that physical activity in pre-pregnancy facilitates the maintenance of epigenetic modifications. Generally, these results strongly suggest that physical exercise before pregnancy is in favor of the later embryo development.