| dc.description.abstract | Even embryonic spacing and migration, the movement and positioning of embryos in the uterine horn prior to implantation, has been previously characterized as the even arrangement of embryos along a single uterine horn. This preimplantation process has been described as a conserved, tightly regulated phenomenon important for healthy pregnancies in many multiparous species including swine, sheep, goats, rabbits, mice, and rats. In addition, spacing and migration is thought to play a significant role in early pregnancy of non-polytocous species, such as humans and bovine. Abnormalities in spacing and migration can result in growth restriction, morbidity, mortality, and abortion/reabsorption in many polytocous species. In humans, uneven spacing and migration of embryos have been suggested to contribute to ectopic pregnancies, placental previa, sharing of the placenta, and twin-twin transfusion syndrome, which can result in the increased risk of growth restriction, malformations of the heart, perinatal mortality, and embryo morbidity. Using a mouse model, illumination of genetic components associated with uneven spacing provides insight into mechanisms and pathways that drive pre- and peri-implantation events.
To elucidate genetic mechanisms associated with embryonic spacing and migration, C57BL/6J, C3HeB/FeJ, and C3H/HeJ strains of mice were used (to define the model), in which, C57BL/6J represented a population of mice with evenly spaced embryos, whereas C3HeB/FeJ and C3H/HeJ represented populations with unevenly spaced embryos. Pedigree analysis suggested that both maternal and embryonic genetic contributions affect this process with an emphasis on a maternal effect and dominance gene action. Several other assays were conducted in order to determine if any physiological mechanisms contribute to uneven embryo spacing, including sex of the embryo, parity (primigravida vs. multigravida pregnancies), and timing of implantation. None of the tested physiological mechanisms explained the uneven spacing observed in the two C3H strains. Additionally, quantitative trait loci analysis was performed on data collected from 12 recombinant inbred lines, generated from C57BL/6J and C3H/HeJ. These data led us to several regions of interest on chromosomes 13 and 9. Additionally, RNAseq, led to further elucidation of differentially expressed genes from E3.5 embryos. Furthermore, future research will refine the understanding of the genetic mechanism(s) in embryo spacing and migration are controlled. | en |
