Effects of mtDNA haplotype on conceptus phenotype in cattle at midgestation

Abstract

Mitochondria are indispensable for fetal development because of the high energy demand of metabolic processes and growth. The mitochondrial genome can be clustered into groups according to the phylogenetic origins of maternal lineages, known as mtDNA haplotypes. In animals, mtDNA haplotype has been associated with tolerance to heat, growth, meat and milk quality and fertility. Sex-associated differences in mitochondrial function have been reported. However, data regarding the relationship between mtDNA haplotype and fetal phenotype, and whether this differs between sexes, is lacking. Our study employed 49 male and female bovine concepti with Bos taurus (Bt) or Bos indicus (Bi) mtDNA haplotype to examine effects of mtDNA haplotype and sex on conceptus traits at midgestation (Day 153). Traits assessed included fetal weight, organ weights, fetal muscle immunohistochemistry, relative mtDNA content of fetal tissues, clinico-chemical composition of amniotic and allantoic fluid, and maternal and fetal serum. Fetal liver mitochondrial proteome was studied in 10 concepti with either Bt or Bi mtDNA haplotype. Fetal phenotype, relative mtDNA content of fetal tissues and placenta were not affected by mtDNA haplotype, except muscle tissue. Concepti with Bt mtDNA haplotype had greater relative mtDNA content in M. semitendinosus muscle and lower fast myotube cross-sectional area compared to those with Bi mtDNA haplotype. Magnesium concentrations in amniotic fluid and magnesium, glucose, lactate and glutamate dehydrogenase in allantoic fluid were higher in concepti with Bi mtDNA haplotype, compared to Bt haplotype. Conceptus mtDNA haplotype did not affect clinico-chemical parameters in fetal serum, but glucose and aspartate transaminase (AST) were higher in serum of dams carrying a Bi haplotype concepti. In contrast, total protein was higher in serum of dams with Bt haplotype concepti. The mitochondrial proteome of fetal liver mitochondria had 946 proteins and microsomal glutathione transferase 1 abundance was lower in female Bi haplotype concepti than in Bt haplotype concepti. Regarding fetal sex effects, male fetuses had higher body weight and organ weights, except brain weight, compared to the females, regardless of mtDNA haplotype. In Bi mtDNA haplotype concepti, mtDNA content of brain was higher in male than female fetuses. In Bt concepti, calcium, glucose and AST were higher in amniotic fluid of females than males. In contrast, in Bi mtDNA haplotype concepti, concentrations of calcium, magnesium, and creatinine were higher in amniotic fluid of males. Amniotic fluid D-3 hydroxybutyrate was lower in female concepti than males in both mtDNA haplogroups. Fetal sex did not significantly affect clinico-chemical parameters in allantoic fluid. Serum D-3 hydroxybutyrate was higher in female than male fetuses with Bt mtDNA haplotype, while serum ALP was higher in females than males with Bi mtDNA haplotype. Serum creatinine of dams with a female Bi haplotype conceptus, was higher than in those with a male conceptus. In conclusion, this study provides important insights into relationships between conceptus mtDNA haplotype and bovine fetal development at midgestation. To advance our understanding of these relationships, future analyses of conceptus mtDNA haplotype effects on placental factors, transport of electrolytes, metabolites and enzymes between fetal fluids and fetal-maternal circulation and the fetal liver mitochondrial proteome with a larger number of concepti are required.