The corpus luteum (CL) is a temporary, heterogeneous endocrine gland that develops cyclically in mature females after ovulation. If the oocyte is not fertilized, CL stops releasing hormones and undergoes luteolysis [1]. On the other hand, if fertilization occurs, CL continues secretory activity. The most important hormone produced by CL is progesterone (P4), whose production during the luteal phase determines the menstrual/estrous cycle course and the receptivity of the endometrium to successful implantation and is critical for maintaining an early pregnancy [2]. Therefore, the underlying endocrine, autocrine/paracrine, and molecular mechanisms controlling the precise progression of the luteal phase are of paramount importance in distinguishing between a fertile and an infertile cycle. The CL is an essential structure regulating the reproduction in mammals, especially in these species where it is the main source of P4 during pregnancy (e.g., pigs) [3].

PPARs are nuclear receptors that regulate gene expression related to glucose, lipid, and protein metabolism [4]. To date, three PPAR isoforms have been identified as α, β/δ, and γ. PPARs are ligand-dependent structures activated by endogenous (polyunsaturated fatty acids and arachidonic acid derivatives) and exogenous (fibrates, thiazolidinediones-TZDs, nonsteroidal anti-inflammatory drugs) ligands. Some of the ligands are used in the treatment of type 2 diabetes, polycystic ovary syndrome (PCOS) (TZDs) or lipid disorders (fibrates). Their importance in the control of reproductive processes is also highlighted [[5], [6], [7]]. Available data indicate that the presence of PPARs in luteal cells of cattle seems to be dependent on the phase of the estrous cycle [8]. The results of our previous study showed that PPARs (β, γ) are involved in the secretion of prostaglandins (PGs) – PGE2 and PGF2α – in pigs CL during the estrous cycle, and might play luteotropic role [9]. Studies on porcine and human CL have shown that PPARs are involved in the synthesis of enzymes related to steroidogenesis, such as 3-hydroxysteroid dehydrogenase (3-HSD) and P450 aromatase [10]. In the rat and bovine ovary, PPARs also play a role in the control of angiogenesis via promoting expression of factors such as vascular endothelial growth factor (VEGF) [10,11]. In our previous in vitro study, we determined the global proteome profile of the porcine CL after PPARγ ligands treatment using LC-MS/MS analysis. This analysis revealed proteins involved in the endoplasmic reticulum stress, protein metabolic processes, organization or biogenesis of cellular components and vesicle-mediated transport [12].

Based on our previous research, we hypothesize that PPARγ ligands alter the transcriptomic profile of porcine CL. The aim of the present study was to investigate the in vitro effect of PPARγ ligands (agonist or antagonist) on the profile of differentially expressed genes in the porcine CL in the mid- (day 10–12) and late-luteal (day 14–16) phase of the estrous cycle. In addition, transcriptomic differences between the phases of the cycle were determined.