KIRREL is differentially expressed in adipose tissue from ‘fertil+’ and ‘fertil−’ cows: <i>in vitro</i> role in ovary?

We have previously shown that dairy cows carrying the 'fertil-' haplotype for one quantitative trait locus affecting female fertility located on the bovine chromosome three (QTL-F-Fert-BTA3) have a significantly lower conception rate and body weight after calving than cows carrying the 'fertil+' haplotype. Here, we compared by Tiling Array the expression of genes included in the QTL-F-Fert-BTA3 in 'fertil+' and 'fertil-' adipose tissue one week after calving when plasma non-esterified fatty acid concentrations were greater in 'fertil-' animals. We observed that thirty-one genes were overexpressed whereas twelve were under-expressed in 'fertil+' as compared to 'fertil-' cows (<i>P</i> < 0.05). By quantitative PCR and immunoblot we confirmed that adipose tissue <i>KIRREL</i> mRNA and protein were significantly greater expressed in 'fertil+' than in 'fertil-'. <i>KIRREL</i> mRNA is abundant in bovine kidney, adipose tissue, pituitary, and ovary and detectable in hypothalamus and mammary gland. Its expression (mRNA and protein) is greater in kidney of 'fertil+' than 'fertil-' cows (<i>P</i> < 0.05). KIRREL (mRNA and protein) is also present in the different ovarian cells with a greater expression in granulosa cells of 'fertil+' than 'fertil-' cows. In cultured granulosa cells, recombinant KIRREL halved steroid secretion in basal state (<i>P</i> < 0.05). It also decreased cell proliferation (<i>P</i> < 0.05) and <i>in vitro</i> oocyte maturation (<i>P</i> < 0.05). These results were associated to a rapid increase in MAPK1/3 and MAPK14 phosphorylation in granulosa cells and to a decrease in MAPK1/3 phosphorylation in oocyte. Thus, <i>KIRREL</i> could be a potential metabolic messenger linking body composition and fertility.