Phoenixin-14 and its receptor GPR173 in the bovine endometrium: Expression and regulation during the estrous cycle and impact on secretory activity

The endometrium remodels during the estrous cycle due to many endogenous factors. Phoenixin (PNX)-14 is a relatively recently discovered neuropeptide with a pivotal role in reproduction, specifically in follicle development and the functioning of the corpus luteum and uterus. Our study aimed to determine (1) the expression of PNX-14 and G protein-coupled receptor 173 (GPR173) in the bovine endometrium during the estrous cycle, (2) the cellular localization of PNX-14 and GPR173, (3) the effect of luteotropic and luteolytic factors on PNX-14 and GPR173 expression in the endometrium, and (4) the impact of PNX-14 on the secretory activity of the endometrium. The ex vivo experiments used bovine uterine tissues collected from the four stages of the estrous cycle (days 2-5, 6-10, 11-16, and 17-20). The in vitro experiments used uteri collected from days 10-12 of the estrous cycle. The mRNA expression of small integral membrane protein 20 (SMIM20) and protein expression of PNX-14 was upregulated on days 6-10 of the estrous cycle. GRP173 protein expression was significantly higher on days 11-16. The concentration of PNX-14 in endometrial tissue homogenate was significantly lower on days 17-20 compared to all other days of the estrous cycle. In immunofluorescence analysis, luminal and glandular epithelium and endothelial cells of blood vessels were positive for PNX-14 and GPR173. Progesterone upregulated the mRNA expression of SMIM20 in the bovine endometrium, whereas progesterone and oxytocin upregulated GPR173 mRNA and protein expression. Treating endometrial slices with PNX-14 enhanced prostaglandin E2 secretion. In conclusion, these findings indicate that PNX-14 targets the bovine endometrium and should be considered a locally acting regulator of endometrium function in non-pregnant cows.