The Role of Peroxisome Proliferator-Activated Receptors in PGF2α-Induced Luteolysis in the Bovine Corpus Luteum

Simple Summary The corpus luteum (CL) is responsible for progesterone (P-4) secretion. In the absence of pregnancy, luteolysis occurs, which leads to a reduction in P-4 production, followed by the structural regression of the CL. In cows, prostaglandin F-2 alpha (PGF(2 alpha)) is the main luteolytic factor. It is also an endogenous ligand for peroxisome proliferator-activated receptors (PPARs), which are important factors regulating mammalian reproductive function. However, the mechanisms of action of PPAR isoforms, i.e., PPAR alpha, PPAR delta and PPAR gamma, in the luteolytic pathways in cattle are still not fully understood. The aim of this in vitro study was to determine the expression of PPAR isoforms in the bovine CL throughout the estrous cycle, and their involvement in PGF(2 alpha)-induced processes related to luteolysis. The obtained results indicate that the expression of PPARs changes in the bovine CL throughout the estrous cycle; moreover, PGF(2 alpha) affects its expression. This study provides evidence that PPAR gamma, among all examined PPAR isoforms, could be involved in the regulation of PGF(2 alpha)-induced luteolysis in cattle, and PPARs may affect CL regression at multiple sites. These results help to widen the knowledge of the mechanisms of luteal regression in the bovine CL. The participation of peroxisome proliferator-activated receptors (PPARs) in ovarian function in cattle is still not fully understood. The aim of this in vitro study was to determine: (i) the immunolocalization, mRNA expression and tissue concentration of PPAR alpha, PPAR delta and PPAR gamma in the bovine corpus luteum (CL) (n = 40) throughout the estrous cycle, and (ii) the involvement of PPAR in PGF(2 alpha)-induced processes related to luteolysis. CL (n = 9) explants were cultured in the presence of PPAR antagonists (10(-5) M) in combination with or without PGF(2 alpha) receptor antagonist (10(-5) M) and PGF(2 alpha) (10(-6) M). The mRNA and protein expression of PPARs was evaluated through qPCR, IHC, and ELISA, respectively. The results showed that PPAR mRNA and protein expression differed according to the luteal stages. PGF(2 alpha) upregulated PPAR delta and PPAR gamma mRNA expression in the bovine CL in vitro, whereas PPAR gamma increased the inhibitory effect of PGF(2 alpha) by decreasing progesterone secretion and the mRNA expression of hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 (HSD3B1) in the CL explants; mRNA transcription of tumor necrosis factor alpha (TNF alpha) and inducible nitric oxide synthase (iNOS) was increased. The obtained results indicate that the mRNA and protein expression of PPARs changes in the bovine CL throughout the estrous cycle and under the influence of PGF(2 alpha). We suggest that isoform gamma, among all examined PPARs, could be a factor involved in the regulation of PGF(2 alpha)-induced processes related to luteolysis in the bovine CL. Further studies are needed to understand the role of PPAR in luteal regression in the CL of cattle.