Unveiling the equine placental transcriptome: A novel study on ICSI-derived pregnancies.

This research studied how horse embryos develop when created by intracytoplasmic sperm injection (ICSI) compared to natural conception. The study found significant differences in gene expression and biological processes linked with potential problems for the foetus and newborn.

Research Aim and Methodology

• The aim of the study was to understand the impact of using Intracytoplasmic Sperm Injection (ICSI), a popular commercial artificial reproductive technique (ART) in horses, on the development of the fetus. This was based on the assumption that alterations at the early stages of embryo development could result in long-term effects on the fetus, neonate, and even adult animals. A key aspect of this was studying the “transcriptome” of the placenta – the complete set of RNA molecules expressed from the genes of the placenta.
• The study compared naturally conceived pregnancies (in vivo) versus those conceived using ICSI (in vitro), and observed any disruptions in gene expression of the horse placenta. 17 warmblood mares were used in the study, with 8 naturally bred, and 9 implanted with ICSI-created embryos.
• The health of the pregnancies was monitored, and upon birth, the chorioallantois (part of the horse placenta) collected for further examination. The RNA molecules were isolated and then analyzed using RNA sequencing.

Results of the Study

• The study found that there were 1589 genes that were differently expressed when comparing in vivo versus in vitro-produced embryos. This systemic upregulation and downregulation of genes indicates that using in vitro methods significantly changes the transcriptome of horse placenta.
• Focusing on specifics, some impacted gene ontology elements included essential parts of the central processes of molecular biology such as ribosome biogenesis and RNA polymerase activity, and the spliceosome function.
• More importantly, there were also disruptions of critical biological processes relevant to the immune system related to auto-immunity and irregular antigen response. There were specific disruptions to the IL-17 signaling pathway, a disruptor of rheumatoid arthritis, and lupus, potentially increasing the risk of these conditions in the newborns.
• The research also identified that in vitro-produced pregnancies were associated with hypoxia (inadequate oxygen levels) and issues with ribosome biogenesis (the production of ribosomes).

Study Conclusions

• The results indicate that ICSI, or more generally in vitro-produced pregnancies in horses, could lead to significant disruptions in the placental transcriptome, potentially causing poor fetal and neonatal outcomes. This is consistent with previous observations related to ART in other species and is indicative of the potential risk posed by the widespread commercial use of ICSI in horse reproduction. While further research is needed, this study provides a framework for understanding placental dysregulation’s physiological consequences and its potential impact on horse health.