Identification of sex-dependent epigenetic signatures of the bovine conceptus associated with its developmental potential and its response to different maternal microenvironment during early elongation stage

• Applicant: Professor Dr. Michael Hölker, since 11/2019
• Subject Area: Animal Breeding, Animal Nutrition, Animal Husbandry
• Term: from 2018 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 416743682

Embryo loss during the peri-implantation period is one of the major problems limiting the fertility of high yielding dairy cows. When looking into the sex of the embryos, although the sex ratio is nearly 50% at conception, several lines of evidences including the work of Roche et al. (2006) indicated a skewed male to female ratio at birth. This suggests that embryo of one sex could survive better than the other one when animals are under physiological or metabolic stress. This phenomenon is believed to be largely regulated by DNA methylation and miRNAs in a spatio-temporal manner. However, sex specfic DNA methylation and miRNAs expression patterns, which are associated with conceptus elongation and implantation, remain unknown. Moreover, whether the sex of one conceptus could signal its presence to the maternal environment more strongly than the other one by modifying its epigenetic marks needs to be elucidated. Moreover, the epigenetic response of the male or the female conceptus to different maternal environments and the extent of epigenetic divergence between the two conceptuses within similar maternal environment need further study. Therefore, to wire up all these key questions and to draw logical conclusions, we hypothesize that implantation competent female and male conceptuses are enriched with unique epigenetic marks at the time of the initiation of elongation. Moreover, during this stage, the female or male conceptus alters their epigenetic marks in response to the maternal environment that is attributed by the physiological condition of the animal. Therefore, the main goal of this project is dedicated to investigate the sex specific epigenetic markers of the conceptus that could potentially favor or disrupt its elongation and implantation. Moreover, it is aimed to investigate the DNA methylome and miRNome signatures induced differently in female or male conceptus due to differences in physiological status of animals. For this, we will analyze the DNA methylome and miRNome markers of day 13 female or male conceptuses that could subsequently favor or disrupt its further elongation and implantation using biopsies taken from the conceptus. Following this, the sex specific DNA methylome and miRNome signatures induced in day 13 conceptus due to physiological condition of animals will be investigated using the female and male conceptuses samples developed in multiparous cows and nulliparous heifers. Further candidate differentially methylated genomic regions and miRNAs will be selected will be further validated using bisulfite sequencing and quantitative polymerase chain reaction (qPCR). Finally, the interdependency of the DNA methylome, miRNome and transcriptome during embryo elongation will be analyzed. Moreover, the involvement of those genomic regions and miRNAs in response of male and female conceptus to maternal environment will be investigated.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Karl Schellander
• Ehemaliger Antragsteller: Privatdozent Dr. Dawit Tesfaye, until 11/2019