Brett R. White
Date of this Version
A thesis presented to the faculty of the Graduate College at the University of Nebraska in partial fulfillment of requirements for the degree of Master of Science
Major: Animal Science
Under the supervision of Brett R. White
Lincoln, Nebraska, December 2023
The neuropeptide, kisspeptin, has emerged as a key regulator in pubertal onset. Investigating kisspeptin in pigs has dual benefits: characterizing its effects on pubertal attainment and developing castration alternatives, leading to the generation of a kisspeptin- edited (KISS1-edited) line of pigs. Therefore, our first study aimed at characterizing the growth and reproductive development of the F1 generation of the KISS1-edited pigs. Our second and third studies aimed to target different levels of the hypothalamic-pituitary- gonadal axis with various hormone agonists will allow us to understand how the KO animals respond to activation of different parts of the axis. It was determined that one functional copy of the KISS1 allele (KISS1+/+ and KISS1+/-, respectively) allow for the development of the reproductive axis, testis and ovaries, and boar taint. Conversely, the elimination of both KISS1 alleles (KISS1-/-), results in hypogonadotropic hypogonadism and a complete reduction in androstenone and skatole. In the second and third studies, a KISS1R agonist (C6), NK3R agonist (senktide), GnRHR agonist (Cystorelin) and LHR agonist (hCG) were administered to F1 KISS1-edited boars and gilts (> 250 d of age). The KISS1+/+ and KISS1+/- animals responded normally, whereas the KISS1-/- animals failed to respond to all treatments. This data suggests that intervention of hormone agonists may need to occur earlier. Additionally, the lack of increase of gonadotropins from treatments targeting the hypothalamus and anterior pituitary observed may be due to the lack of GnRH priming to allow for the anterior pituitary to produce sufficient stores of gonadotropins. Frequent injections of GnRH failed to stimulate ovulation and testosterone in gilts and boars, respectively. The results suggest that the prolonged absence of kisspeptin signaling prevents the anterior pituitary and/or gonads from functioning properly. Consequently, molecular characterization of these KISS1-edited pigs is warranted to determine the underlying mechanisms behind the lack of response seen in the KISS1-/- gilts and boars.
Advisor: Brett R. White