William W. Thatcher, Ph.D.
Graduate Research Professor &
University of Florida
Department of Animal Sciences
M.S., University of Maryland
PhD, Michigan State University
Sabbatical, INRA, Nouzilly, France

Dr. W.W. Thatcher's Homepage

A major problem experienced by U.S. dairy producers is poor reproductive efficiency in cattle. Program efforts are to investigate causes of poor fertility in cattle, and from such basic knowledge, develop systems to improve reproductive efficiency at the commercial production unit. Such efforts will contribute to a better understanding of basic processes controlling reproduction and increase the efficiency of production (milk and meat) for human consumption. The program is interdisciplinary in nature to develop a meaningful and visionary program for research and graduate training.

Ovulation Control: Reduced expression of estrus in lactating dairy cows is attributable partially to altered ovarian follicular dynamics compared to non-lactating dairy cows; these alterations are attributable to altered hormonal and metabolic responses associated with the demands of lactation. We have developed a system of ovulation control (Timed Insemination) that integrates recruitment and development of a dominant follicle with induction of CL regression and final induction of ovulation that permits a timed insemination without the need of estrus detection. Timed artificial insemination provides the opportunity to control time of insemination and to present all cows for insemination at a given day to increase herd reproductive efficiency. Even more important, the system provides a basis for us to design future strategies to increase pregnancy rates. Current efforts are to improve CL development and embryo survival with the use of GnRH implants to induce ovulation and alter subsequent corpus luteum development and follicle dynamics. Injection of bovine growth hormone at the beginning of the program increases pregnancy rates in lactating dairy cows. In depth studies are in progress to examine the mechanism of growth hormone action to increase pregnancy rates. A controlled ovulation program with normal fertility provides the basis for increasing experimental sensitivity to examine other reproductive windows that are amenable to increase fertility.

Embryo Survival: A major detriment to high fertility in dairy cattle is the high rate of embryo death and a major program effort focuses on characterizing the normal hormonal and biochemical development of the bovine conceptus. Bovine conceptuses produce very small amounts of estrogens, metabolize progesterone in a manner distinctly different than adjacent endometrial tissues and secrete a specific protein identified as interferon-J. Interferon -tau will maintain the corpus luteum by reducing uterine secretion of PGF2-alpha . At the present time, experiments are underway to understand the signal transduction system and alterations in gene expression that lead to the decrease in PGF2-alpha secretion. Interferon-tau acts through the JAK-STAT pathway. In cattle we feel that the antiluteolytic effect of interferon- tau is not mediated solely through an attenuation in oxytocin receptors. Attenuation in the expression of the estradiol receptor and subsequent alterations in lipid metabolism are likely candidates for the manifestation of interferon-tau induced antiluteolytic effects. We are examining details of the signal transduction system that is activated with interferon-tau , and identifying candidate genes such as the estradiol receptor, PLA2, and Cox 2, that may be regulated by interferon-tau . Coupled with this program effort is the feeding of by-pass fatty acids to increase uterine pool size of fatty acids that will inhibit PGF2-alpha secretion. Fish oils contain long chain fatty acids that inhibit cyclooxygenase activity and these fatty acids are not readily biohydrogenated in the rumen. Thus the concept of feeding an antiluteolytic fat diet to improve embryo survival is under investigation. We know that certain types of fats such as fish oils will decrease uterine secretion of PGF2-alpha when fed and current field trials look promising relative to increases in pregnancy rate. Regulation of gene expression by fatty acids is under investigation.

Postpartum Lactating Dairy Cows: The metabolic and hormonal responses of dairy cows to lactation is a vital area for investigation to further stimulate lactational and reproductive performance. It is clear that bovine growth hormone has a major regulatory control on lactational performance in dairy cows. However, our studies indicate that bovine growth hormone also alters follicular function. Indeed postpartum cows that cycle early in the postpartum period have higher plasma concentrations of IGF-1 compared to anestrous cows. This suggests that perhaps the growth hormone-insulin growth factor system is impaired in lactating dairy cows under a greater negative energy status. Our current investigations are testing this hypothesis. Indeed we have recently shown that injection of recombinant bovine growth hormone into lactating dairy cows at the time we initiate a timed insemination program stimulates fertility. We are investigating the mechanism(s) by which growth hormone may mediate this effect on the ovarian follicle, corpus luteum or growth of the embryo. An additional exciting area under current investigation is our ability to program ovarian follicle development at 7 days postpartum to avoid early ovulations and increases in progesterone that may reduce the uterine immune response and predispose the cow to uterine infections during the normal period of uterine involution. performance.

Heat Stress: Recently, we have shown that detrimental heat stress effects on the ovarian follicle may be partially ablated by repeated injections of GnRH that luteinize or induce atresia of damaged follicles and allow recruitment of healthy follicles. This hypothesis is based upon our examination of aromatase activities in granulosa cells, and molecular markers that we can measure within either granulosa cells or follicular fluid that are indicative of follicle status e.g., HSP90, IGFBP 2, 3 and 4, estradiol and progesterone. Our field studies indicate that a timed insemination increases fertility of heat stressed dairy cows but that this effect is sustained beyond first insemination and may be related to improving follicle quality by induction of turnover of damaged follicles.

Representative Publications:

Binelli, M., J. Hampton, W.C. Buhi and W.W. Thatcher. 1999. Persistent dominant follicle alters pattern of oviductal secretory proteins from cows at estrus. Biol. Reprod. 61: 127-134.

Diaz, T., E.J.-P. Schmitt, R.L., M.-J. Thatcher and W.W.Thatcher. 1998. Human Chorionic Gonadotropin-induced alterations in ovarian follicular dynamics during the estrous cycle of heifers. J. Animal Sci. 76: 1929-1936.

W.W. Thatcher, M. Binelli, J. Burke, C.R. Staples, J.D. Ambrose and S. Coelho. 1997. Antiluteolytic signals between the conceptus and endometrium. Theriogenology 47:131-140.