4. Advancing in Vitro Embryo and Calf Production with the Power of Multiomics and Systems Biology.

Abstract

Genomics and selective breeding programs have contributed to substantial genetic improvement of cattle over many decades. In parallel, artificial reproductive technologies (ART) such as in vivo and in vitro embryo / calf production have contributed to faster genetic gain. Both cattle breeding and ART have advanced rapidly in the last decade but the opportunities for a holistic cattle production lies in bridging and implementing these two technologies effectively. While multiple ovulation and embryo transfer (MOET) programs are widely applied by breeding companies world-wide, Ovum Pick Up – In vitro Fertilization (OPU-IVF) are increasingly being used because it has many distinct advantages over MOET. Hence, OPU-IVF-In vitro-produced (IVP) embryos continue to surpass MOET embryos worldwide. However, there is an increased concern about the current drawbacks of IVP embryos, calves, lower pregnancy rates compared to MOET. We have conducted several long-term projects employing powerful multiomics-driven reproductive systems biological investigation of MOET vs. IVP embryos as well as calves and studied the impact of donor sperm epigenetic make-up on their IVP embryos’ multiomics and its development. My talk will focus on such investigations. The first part of the talk covers oocyte donor and recipient cattle encompassing integrated systems genetics/genomics, epigenomics and transcriptomics analyses. Integrative genetics-epigenomics-transcriptomics analyses delivered key insights into molecular determinants and regulatory features, highly predictive biomarker genes and associated / impacted molecular pathways underlying the key differences between IVP vs. MOET embryos and calves. Second part of my talk covers study on multi-tissue transcriptomics of six different organs of 3-month-old dairy calves produced using MOET and IVP. Results show IVP calves are exposed to metabolic reprogramming and maintenance trade-offs and their regulatory architecture in the HPA axis is significantly fragmented by the IVP procedure than MOET. Expression QTLs (eQTLs) regulating transcriptional programs across multi-tissues in IVP and MOET calves show that there are key differences in genome-wide genetic regulation. Third part of my talk focus on how elite bull semen's epigenetic changes affect IVP embryo's methylome, transcriptome and its development. Results show if donor’s sperm methylation profiles are very different, it results in differential epigenetic reprogramming in embryos and affects downstream gene expression and gene co-expression networks. These deeper insights and mechanistic understanding of key differences of in vivo and in vitro embryos and calves and impact of bull’s sperm epigenetics on embryos are made possible by powerful integrative multiomic modelling techniques and bioinformatics analyses. Talk concludes with implications and future directions in In Vitro Embryo and Calf Production.