A single nucleotide polymorphism in COQ9 affects mitochondrial and ovarian function and fertility in Holstein cows†

Abstract

A single missense mutation at position 159 of coenzyme Q9 (COQ9) (G→A; rs109301586) 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, interval from calving to conception, and services per conception. There was no association of genotype with milk production or body weight changes postpartum. The mutation in COQ9 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 antimullerian hormone concentrations. Overall, results show how a gene involved in mitochondrial function is associated with overall fertility, possibly in part by affecting oocyte quality.

Interactions of human chorionic gonadotropin with genotype and parity on fertility responses of lactating dairy cows

“…COQ9, along with other COQ proteins (COQ2-COQ8), is involved in the biosynthesis of COQ10 (Tran and Clarke, 2007;Ben-Meir et al, 2015), which is a component of the mitochondrial electron transport system that is required for mitochondrial adenosine triphosphate synthesis. The A allele, which has a frequency of 49 to 51% in Holsteins (Ortega et al, 2016a), is associated with enhanced mitochondrial function (Ortega et al, 2017c). One possibility is that actions of hCG on reproductive tissues such as the endometrium (Shemesh et al, 2001) and corpus luteum (Niswender et al, 2000) have negative consequences when mitochondrial function is enhanced.…”

“…One SNP is an G → A missense mutation in coenzyme Q9 (COQ9) that causes an amino acid change from aspartic acid to asparagine at position 53 of the protein. The A allele is associated with higher genetic merit for daughter pregnancy rate (DPR) and cow conception rate (Cochran et al, 2013b;Ortega et al, 2016a) and higher phenotypic measurements of fertility (Ortega et al, 2017c). The A allele is also associated with more efficient mitochondria in peripheral blood mononuclear cells, and increased mitochondrial DNA copy number in oocytes (Ortega et al, 2017c).…”

“…The A allele is associated with higher genetic merit for daughter pregnancy rate (DPR) and cow conception rate (Cochran et al, 2013b;Ortega et al, 2016a) and higher phenotypic measurements of fertility (Ortega et al, 2017c). The A allele is also associated with more efficient mitochondria in peripheral blood mononuclear cells, and increased mitochondrial DNA copy number in oocytes (Ortega et al, 2017c). Heterozygotes had increased follicle number and antimullerian hormone concentrations than either homozygote (Ortega et al, 2017c).…”

“…The A allele is also associated with more efficient mitochondria in peripheral blood mononuclear cells, and increased mitochondrial DNA copy number in oocytes (Ortega et al, 2017c). Heterozygotes had increased follicle number and antimullerian hormone concentrations than either homozygote (Ortega et al, 2017c). The second SNP is a cytosine deletion in the promoter region of heat shock protein 70 kDa protein 1-like (HSPA1L), which encodes for a member of the heat shock protein 70 family.…”

Role of ROCK signaling in formation of the trophectoderm of the bovine preimplantation embryo

“…Embryos used for this study were produced in vitro following the procedures previously described (Ortega et al, ). Each replicate was from a single in vitro fertilization procedure using 200–300 cumulus‐oocyte‐complexes and a pool of sperm from three bulls.…”