The principal area of research focus is the elucidation of the cellular and molecular processes by which cellular stress disrupts embryonic function and the intercellular defense systems that embryos use to limit these effects. Research in the laboratory demonstrated that preimplantation embryonic development is disrupted by exposure to elevated temperature and that embryos acquire resistance to elevated temperature as they proceed through development. It was also shown that embryonic resistance to heat shock is controlled by genetic factors, with embryos from Bos indicus being more resistant to heat shock than embryos from B. taurus. Moreover, embryonic thermotolerance can be enhanced by manipulating heat shock protein synthesis and treatment with the survival factor, insulin-like growth factor-1. My current focus is on understanding the molecular basis for these determinants of thermotolerance with emphasis on the role of apoptosis, heat shock protein synthesis, and free radical metabolism.
Applied studies have used the knowledge gained from studies of embryo physiology to develop new management strategies for increasing dairy cattle fertility. In embryo transfer schemes, embryos are typically transferred to recipients at a stage of development at which they have acquired substantial resistance to heat shock. It has been demonstrated in the laboratory that pregnancy rate during periods of heat stress can be improved through the use of embryo transfer. Increasing fertility during heat stress has been a difficult task and embryo transfer represents the first successful approach to doing so. Current research is devoted to improving the practicality of using embryo transfer as a tool for enhancing fertility in dairy cattle exposed to heat stress or with low fertility. Much of the new focus in the laboratory is on understanding how maternally derived molecules like CSF2 and IGF1 can alter the pattern of preimplantation development to enhance embryonic and fetal survivial.
A second area of research is focused on immunological interactions between the conceptus and mother. Much of this work centers on progesterone since this hormone plays an important role in suppressing uterine immune function during pregnancy. It is believed progesterone acts, at least in part, by inducing secretion of other molecules that inhibit lymphocyte proliferation. In sheep, the model species for much of the work, this molecule has been identified as a protein called ovine uterine serpin. Recently, it was shown that ovine uterine serpin can also inhibit growth of several tumor cell lines and an emerging area of research will be to characterize the mechanism and test possible anticarcinogenic properties of the protein.
A third area of research focuses on understanding the molecular correlates of the evolutionary development of the epitheliochorial placenta. Work has focused on phylogenetic changes in the uterine serpin genes.
Finally, efforts are being initiated to understand the genetic control of fertility and thermotolerance.
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Sakatani, M., Bonilla, L., Dobbs, K.B., Block, J., Ozawa, M., Shanker, S., Yao, J.-Q., and Hansen, P.J. (2013) Changes in the transcriptome of morula-state bovine embryos caused by heat shock: relationship to developmental acquisition of thermotolerance. Reprod. Biol. Endocrinol. 11, 3.
Denicol, A.C., Dobbs, K.B., McLean, K.M., Carambula, S.F., Loureiro, B., and Hansen, P.J. (2013) Canonical WNT signaling regulates development of bovine embryos to the blastocyst stage. Sci. Rep. 3, 1266.
Dobbs, K.B., Rodriquez M., Sudano, M.J., Ortega, M.S. and Hansen, P.J. (2013) Dynamics of DNA methylation during early development of the preimplantation bovine embryo. PLoS One 8, e66230.
Cochran, S.D., Cole, J.B., Null, D.J., and Hansen, P.J. (2013) Discovery of single nucleotide polymorphisms in candidate genes associated with fertility and production traits in Holstein cattle. BMC Genet. 14, 49.
Dikmen, S., Cole, J.B., Null, D.J., and Hansen, P.J. (2013) Genome wide association mapping for identification of quantiative trait loci for rectal temperature during heat stress in Holstein cattle. PLoS ONE 8, e69202.
Cochran, S.D., Cole, J.B., Null, D.J. and Hansen, P.J. (2013) Single nucleotide polymorphisms in candidate genes associated with fertilizing ability of sperm and subsequent embryonic development in cattle. Biol. Reprod. 89, 69.
Dobbs, K.D., Khan, F.A., Sakatani, M., Moss, J.I., Ozawa, M., Ealy, A.D., and Hansen, P.J. (2013) Regulation of pluripotency of inner cell mass and growth and differentiation of trophectoderm of the bovine embryo by colony stimulating factor 2. Biol. Reprod. 89, 141.
Bonilla, L., Block, J., Denicol, A.C., and Hansen, P.J. (2014) Consequences of transfer of an in vitro produced embryo for the dam and resultant calf. J. Dairy Sci. 97, 229-239.