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ARS Home » Plains Area » Clay Center, Nebraska » U.S. Meat Animal Research Center » Livestock Bio-Systems » Research » Publications at this Location » Publication #426155
Research Project: Improving Lifetime Productivity in Swine using Systems Biology and Precision Management Approaches

Location: Livestock Bio-Systems

Title: Gonadotropin secretion and ovarian response of KISS1 knockout gilts treated with hormone analogs activating the hypothalamic-pituitary-gonadal axis

Author
item AHERN, DANIEL - University Of Nebraska
item WILSON, KYLE - Former ARS Employee
item Wijesena, Hiruni
item ROSS, CAITLIN - University Of Nebraska
item ELSKEN, DOROTHY - University Of Nebraska
item FLOREZ, JULIO - Acceligen Inc
item MARTINS, KYRA - Acceligen Inc
item BELTRAMO, MASSIMILIANO - Universite De Tours
item SONSTEGARD, TAD - Acceligen Inc
item Cushman, Robert
item WHITE, BRETT - University Of Nebraska
item Lents, Clay

Submitted to: Biology of Reproduction
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/21/2025
Publication Date: 8/2/2025
Citation: Ahern, D.F., Wilson, K.E., Wijesena, H.R., Ross, C.E., Elsken, D.H., Florez, J.M., Martins, K., Beltramo, M., Sonstegard, T.S., Cushman, R.A., White, B.R., Lents, C.A. 2025. Gonadotropin secretion and ovarian response of KISS1 knockout gilts treated with hormone analogs activating the hypothalamic-pituitary-gonadal axis. Biology of Reproduction. Article ioaf174. https://doi.org/10.1093/biolre/ioaf174.
DOI: https://doi.org/10.1093/biolre/ioaf174

Interpretive Summary: In pork production, 30% of females called gilts that are selected for replacement breeding animals never produce a litter. This is often because gilts fail to reach puberty in time for breeding, but it is not well understood why this happens. ARS scientists at Clay Center, Nebraska, found that the KISS1 gene was associated with failure of gilts to reach puberty. Using a unique line of pigs in which the KISS1 gene was deactivated with precision gene editing, ARS scientists discovered that KISS1 was essential for secretion of reproductive hormones that stimulate the ovary and cause puberty. Scientists further discovered how KISS1 was regulated and how to overcome the absence of KISS1 to make gilts ovulate. This novel knowledge is critical for developing new methods to improve gilt development and fertility that will reduce economic losses and strengthen U.S. pork producers.

Technical Abstract: Kisspeptin knockout (KISS1-/-) pigs exhibit hypogonadotropic hypogonadism. Hormone analogs targeting different levels of the HPG axis were used to characterize the secretion of reproductive hormones (LH and FSH) and ovarian responses (estradiol and progesterone) in KISS1-/- gilts. Uteri and ovaries were collected from KISS1+/+ and KISS1-/- gilts to confirm ovulatory outcomes. Pulses of LH and FSH were observed in KISS1-/- gilts that differed (P < 0.05) in amplitude and nadir from pulses in wild-type KISS1+/+ and KISS1+/- gilts. A neurokinin B (NKB) agonist stimulated LH but not FSH in wild-type gilts, whereas NKB affected neither LH nor FSH in KISS1-/- gilts. The kisspeptin receptor agonist, C6, stimulated LH secretion in wild-type gilts but not in KISS1-/- gilts (P < 0.05). Secretion of LH in KISS1-/- gilts depends on the dose and frequency of GnRH. Priming with estradiol and GnRH before PMSG and hCG treatment resulted in luteal structures on the ovary of KISS1-/- gilts, though ovulation rate was less (P < 0.05) than KISS1+/+ gilts. This is the first report showing NKB regulation of LH secretion in swine. It is confirmed that a single copy of the KISS1 allele in gilts confers normal gonadotropin secretion following stimulation with NKB, kisspeptin and GnRH analogs. The sustained activation of the kisspeptin receptor by C6 generated long-lasting LH secretion in gilts to induce ovulation. Ovulation in KISS1-/- gilts is possible but treatments need optimization for a standard ovulation rate.