Dr. Cupp’s laboratory focuses on how to improve male and female fertility by understanding major problems that cause infertility. In the female, a major problem is not ovulating or ovulating at an inappropriate time that leads to problems with implantation and embryo development. Her laboratory has determined that within the UNL physiology herd there is a population of females (High A4) that have increased androgens in follicular fluid, irregular reproductive cycles (they either do display estrus and ovulate; or they ovulate without displaying estrus; or neither ovulate or display estrus). Interesting, when they do not ovulate they develop follicles that persist for extended periods of time and potentially have aged eggs which may not be able to be fertilized. These females have a 17% reduction in calving rate and also have gene expression profiles that are similar to women with Polycystic Ovary Syndrome. These High A4 cows have reduced Sex Hormone Binding Globulin (SHBG). Sex Hormone Binding Globulin is a protein that binds to steroid hormones-estrogens and androgens, and—basically it inhibits them. If you have too little SHBG then more estrogens and androgens can act on cells and may cause problems (like anovulation). Reduced concentrations of SHBG are also seen in human patients with Type II Diabetes, Chronic Inflammation Disorders, Metabolic Syndrome, Polycystic Ovary Disease, and Fatty Liver Disease. The Sex Hormone Binding Globulin is produced in the liver, so the Cupp lab is trying to understand if the infertility in these cows is due to problems with liver metabolism, altered diets during fetal development, genetic predisposition. These cows stay in the herd as long as they have a calf and it appears that they wean a calf that is 26 pounds heavier than the control cows.
Interestingly these High A4 cows also appear to achieve puberty at an earlier age. Because girls with Polycystic ovary Syndrome are detected at puberty, the Cupp lab decided to evaluate how heifers in the UNL herd established their reproductive cycles. In the second year of this study they have determined that there are heifers that achieve puberty early and also continue to cycle (EARLY), there are heifers that achieve puberty at a later time point and continue to cycle (TYPICAL), and there are heifers that Start early and then stop (START-STOP) and other heifers that do not Cycle (NON-CYCLING). The Cupp lab has determined that the START-STOP and NON-CYCLING groups have less SHBG produced and are currently determining if these groups are the heifers that mainly fall out of the herd due to not producing a calf.
IMPLICATIONS of RESEARCH
Identification of what causes cows to be anovulatory (not ovulate) could have dramatic implications in both dairy and beef herds. It would allow for practices to be developed to either allow them to be more successful in ovulating or selected against to be removed from the herd. At the same time, the Cupp lab is developing a better understanding of how liver metabolism and feed intact may impact reproductive function which will allow for better feeding management programs for cattle herds in Nebraska and the US.
Dr. Cupp collaborates on this research with Drs Wood in the Animal Science Department at UNL; Cushman at US Meat Animal Research Center, John Davis at University of Nebraska Medical Center.