Identification of an ionotropic glutamate receptor AMPA1/GRIA1 polymorphism in crossbred beef cows differing in fertility

Authors: Cushman, Robert - Bob; Miles, Jeremy; Rempel, Lea; McDaneld, Tara; Kuehn, Larry; Chitko-Mckown, Carol; Nonneman, Danny - Dan; Echternkamp, Sherrill

Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/18/2013
Publication Date: 6/1/2013
Citation: Cushman, R.A., Miles, J.R., Rempel, L.A., McDaneld, T.G., Kuehn, L.A., Chitko-McKown, C.G., Nonneman, D., Echternkamp, S.E. 2013. Identification of an ionotropic glutamate receptor AMPA1/GRIA1 polymorphism in crossbred beef cows differing in fertility. Journal of Animal Science. 91(6):2640-2646.

Interpretive Summary: Previous research at USMARC has demonstrated that Repeat Breeder cows that fail to conceive in two consecutive breeding seasons have fewer small antral follicles. A recent report indicated that a functional polymorphism in the ionotropic glutamate receptor AMPA1 (GRIA1) resulted in decreased numbers of antral follicles in cows, and a polymorphism in the gonadotropin releasing hormone receptor (GnRHr) might be associated with increased age at puberty. Therefore, we examined the influence of theses polymorphisms on reproductive traits in Repeat Breeder or Fertile cows. The objective of the current study was to compare reproductive tract size and gene expression in the granulosa cells of the small follicles between Repeat Breeder and Fertile cows. Reproductive tracts were collected at slaughter and returned to the laboratory for evaluation. Repeat Breeder cows were older at first calving than Control cows. Repeat Breeder cows had smaller ovaries with fewer antral follicles than Fertile herd mates. The length and height of the ovary contralateral to the corpus luteum (CL) were greater in Fertile cows than Repeat Breeder cows. The endometrial diameter in the horn ipsilateral to the CL was greater in the Fertile cows than the Repeat Breeder cows. Repeat Breeder cows had fewer small (1-5 mm) antral follicles than Fertile cows; however, there was no association between GRIA1 genotype and antral follicle number. The GnRHR polymorphism associated with age at first calving, because cows that were homozygous for the C allele had a greater age at first calving than heterozygous cows or cows that were homozygous for the T allel. In the granulosa cells from small (1-5 mm) antral follicles, mRNA levels of two markers of oocyte quality, anti-Müllerian Hormone and pentraxin 3, did not differ between fertility groups. We conclude that this GRIA1 polymorphism exists in beef cows, but that it does not influence antral follicle numbers. The association between GnRHR genotype and age at first calving is likely not causal as this polymorphism is not functional. The utility of this polymorphism as a genetic marker for early conception in heifers will require further validation. Screening postpartum cows by ultrasonography to determine antral follicle numbers may aid in making culling decisions.

Technical Abstract: A proposed functional polymorphism in the ionotropic glutamate receptor AMPA1 (GRIA1) has been reported to influence antral follicle numbers and fertility in cows. Repeat Breeder cows that fail to produce a calf in multiple seasons have been reported to have reduced numbers of small (1-3 mm) antral follicles in their ovaries. Therefore, we tested the hypothesis that this GRIA1 polymorphism was affecting antral follicle numbers in Repeat Breeder cows. Repeat Breeder cows (n = 64) and Control cows (n = 72) that had always produced a calf were housed in a dry lot and observed twice daily for behavioral estrus. Blood samples were collected and cows were genotyped for this GRIA1 polymorphism and for a polymorphism in the gonadotropin releasing hormone receptor (GnRHR) that was proposed to influence age at puberty. On d 3-8 after estrus cows were slaughtered and reproductive organs were collected to determine antral follicle count, ovary size, and uterine horn diameter. Repeat Breeder cows were older at first calving than Control cows (P = 0.006). The length (P = 0.03) and height (P = 0.02) of the ovary contralateral to the corpus luteum (CL) were greater in Control cows than Repeat Breeder cows. The endometrial diameter in the horn ipsilateral to the CL was greater in the Control cows than the Repeat Breeder cows. Repeat Breeder cows had fewer small (1-5 mm) antral follicles than Control cows (P = 0.003); however, there was no association between GRIA1 genotype and antral follicle number. The GnRHR polymorphism associated with age at first calving, because cows that were homozygous for the C allele had a greater age at first calving than heterozygous cows or cows that were homozygous for the T allele (P = 0.01). In the granulosa cells from small (1-5 mm) antral follicles, mRNA levels of two markers of oocyte quality, anti-Müllerian Hormone and pentraxin 3, did not differ between fertility groups (P >/= 0.12). We conclude that this GRIA1 polymorphism exists in beef cows, but that it does not influence antral follicle numbers. The association between GnRHR genotype and age at first calving is likely not causal as this polymorphism is not functional. The utility of this polymorphism as a genetic marker for early conception in heifers will require further validation. Screening postpartum cows by ultrasonography to determine antral follicle numbers may aid in making culling decisions.