|Ortega, M. Sofia - University Of Florida|
|Wohlgemuth, Stephanie - University Of Florida|
|Tribulo, Paula - University Of Florida|
|Siqueira, Luiz - University Of Florida|
|Da Silva, Marcus - Embrapa|
|Hansen, Peter - University Of Florida|
Submitted to: Biology of Reproduction
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/31/2017
Publication Date: 2/3/2017
Citation: Ortega, M., Wohlgemuth, S., Tribulo, P., Siqueira, L.G., Null, D.J., Cole, J.B., Da Silva, M.V., Hansen, P.J. 2017. A single nucleotide polymorphism in COQ9 affects mitochondrial and ovarian function and fertility in Holstein cows. Biology of Reproduction. 96(3):652-663.
Interpretive Summary: A single mutation in the COQ9 gene is associated with genetic variation in fertility in Holstein cattle. The COQ9 gene is involved in the synthesis of the coenzyme COQ10 protein, which is expressed in mitochondria. The mitochondria convert sugars from an animal’s diet into chemical energy that is used for many cellular functions. The mutation we observed in COQ9 produces a change in the predicted structure of the COQ0 protein and affects mitochondrial respiration in blood cells. The favorable (A) allele was associated with low resting oxygen consumption and high electron transport system capacity. The A allele is also associated with higher pregnancy rate (+3%), a shorter interval from calving to conception (-8 d), and fewer services per conception (-0.2). Cows with the AA genotype (two copies of the A allele) experienced less severe body weight losses after first calving but not after second calving. The mutation in COQ9 also affected ovarian function, with the A allele resulting in higher oocyte quality. These results show how a gene involved in mitochondrial function can affect overall fertility.
Technical Abstract: A single missense mutation at position 159 of COQ9 (GàA) has been associated with genetic variation in fertility in Holstein cattle, with the A allele associated with higher fertility. COQ9 is involved in the synthesis of coenzyme COQ10, a component of the electron transport system of the mitochondria. Here we tested whether reproductive phenotype is associated with the mutation and evaluated functional consequences for cellular oxygen metabolism, body weight changes, and ovarian function. The mutation in COQ9 modifies predicted tertiary protein structure and affected mitochondrial respiration of peripheral blood mononuclear cells. The A allele was associated with low resting oxygen consumption and high electron transport system capacity. Phenotypic measurements for fertility were evaluated for up to five lactations in a population of 2273 Holstein cows. There were additive effects of the mutation (P < 0.05) in favor of the A allele for pregnancy rate (+3%), interval from calving to conception (-8 d), and services per conception (-0.2). There was no association of genotype with milk production. Cows with the AA genotype experienced less severe body weight losses after first calving but not after second calving. The mutation in COQ9 also affected ovarian function; the A allele was associated with increased mitochondrial DNA copy number in oocytes, and there were overdominance effects for COQ9 expression in oocytes, follicle number and AMH concentrations. Overall, results show how a gene involved in mitochondrial function can modify overall fertility, possibly in part by affecting oocyte quality.