Date of Award

Summer 1998

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Program/Concentration

Biomedical Sciences

Committee Director

R. James Swanson

Committee Member

Keith Carson

Committee Member

Mark Elliot

Committee Member

Sergio Oehninger

Abstract

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine which demonstrates perplexing physiological effects. It has been demonstrated that LIF is essential for implantation in mice. Little is known relating to the manner by which LIF effects pre-implantation and post-implantation development. The objectives of this project were to determine the effects LIF on pre-implantation development, to determine the effects that it may have on implantation rates, successful pregnancy rates, and resorption rates, and to determine the effects that LIF has on the skeletal development of mice. For the embryo transfer experiments, embryos were exposed to test compounds in the transfer medium only at the time of transcervical embryo transfer.

The results obtained from this project illustrate that murine LIF stimulates the development of pre-implantation mouse embryos to the blastocyst stage. Additionally, human LIF and an anti-murine LIF antibody had and inhibitory effect. Dose dependent effects were demonstrated and murine LIF significantly enhanced development in a dose related manner with the highest developmental indices recorded for the highest concentration studied and significance observed for all concentrations. For the transcervical embryo transfer experiments, transfer medium supplemented with 5000 U/ml mrLIF almost doubled implantation, pregnancy, and resorption rates whereas the mcab approximately halved these rates when compared to controls. Finally, it was observed that transfer medium supplemented with 5000 U/ml mrLIF or 5000 U/ml of the anti-mrLIF mcab had profound effects on the skeletal development of mouse fetuses. Murine rLIF significantly reduced the overall length of the cartilagenous bone precursor as well as the length of the ossification centers in the humerus and scapula. The mcab reversed this behavior and actually stimulated both parameter significantly.

The clinical ramifications for LIF use in in vitro fertilization clinics as a medium supplement are obvious and have been suggested by clinicians. The results from this project show that LIF enhances the implantation of, not only healthy embryos, but those that would not normally survive to term. Additionally, a single expose at the time of embryo transfer significantly retards skeletal development in mice. These results warrant further studies before LIF is used in a clinical setting.

DOI

10.25777/kpvq-tx09

ISBN

9780599059573

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