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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 #331001

Title: Use of genetically engineered swine to elucidate testis function in the boar

Author
item DESAULNIERS, AMY - University Of Nebraska
item CEDERBERG, REBECCA - University Of Nebraska
item Lents, Clay
item WHITE, BRETT - University Of Nebraska

Submitted to: Symposium Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 8/12/2016
Publication Date: 10/18/2016
Citation: Desaulniers, A.T., Cederberg, R.A., Lents, C.A., White, B.R. 2016. Use of genetically engineered swine to elucidate testis function in the boar. Large Animal Genetic Engineering Summit. September 18-20 2016, Bethesda, Maryland, p. 15-16, Symposium Proceedings. (2pp).

Interpretive Summary:

Technical Abstract: The second mammalian GnRH isoform (GnRH-II) and its specific receptor (GnRHR-II) are abundant within the testis, suggesting a critical role. Gene coding errors prevent their production in many species, but both genes are functional in swine. We have demonstrated that GnRHR-II localizes to porcine Leydig cells and GnRH-II stimulates testosterone release in vivo despite minimal luteinizing hormone (LH) secretion. These data suggest that GnRH-II directly effects steroidogenesis. To address this hypothesis, GnRHR-II knockdown (KD) swine were produced. During pubertal development, testosterone concentrations were reduced in transgenic compared to littermate control males, but LH levels were unaffected. These data indicate that GnRHR-II KD impairs steroidogenesis directly at the testis instead of via the classical androgen stimulator, LH. Here, our objective was to compare secretory patterns of testosterone between lines (transgenic vs. control). Mature GnRHR-II KD (n = 5) and littermate control (n = 5) boars were fit with indwelling cannulae and blood was collected every 15 min for 8 h. Serum was assayed for testosterone concentration via radioimmunoassay. Boars were euthanized; testis, kidney and body weights were recorded and testicular tissue was collected for quantification of GnRHR-II expression via digital droplet PCR. Body, kidney and testis weights were similar between lines (P > 0.05). We did not detect (P > 0.05) an effect of time or a line by time interaction on testosterone concentrations but there was an effect of line (P < 0.05). Testosterone concentrations were dramatically reduced (82%) in transgenics (0.75 ± 0.05 ng/ml) compared to controls (4.09 ± 0.29 ng/ml). Testicular GnRHR-II mRNA levels were reduced by 69% in transgenics (P < 0.001). These data demonstrate that GnRH-II and its receptor are novel mediators of testosterone secretion in boars, challenging the central dogma of testosterone regulation. Since testosterone secretion classically dictates male reproductive success, GnRH-II and its receptor will likely be targeted to improve fertility in swine. Notably, this swine line represents the first genetically engineered animal model to examine the role of GnRH-II and its receptor in mammals. Supported by NIFA Hatch (NEB-26-199; BRW) and AFRI (2011-67015; CAL) funds.