KIRREL is differentially expressed in adipose tissue from “fertil+” and “fertil-” cows: in vitro 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 over-expressed whereas twelve were under-expressed in "fertil+" as compared to "fertil-" cows (P<0.05). By quantitative PCR and immunoblot we confirmed that adipose tissue KIRREL mRNA and protein were significantly greater expressed in "fertil+" than in "fertil-". KIRREL 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 (P<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 (P<0.05). It also decreased cell proliferation (P<0.05) and in vitro oocyte maturation (P<0.05). These results were associated to a rapidly increase in MAPK1/3 and MAPK14 phosphorylation in granulosa cells and to a decrease in MAPK1/3 phosphorylation in oocyte. Thus, KIRREL could be a potential metabolic messenger linking body composition and fertility.