Peroxisome proliferator-activated receptors (PPARs) belong to a ligand-dependent nuclear receptor family. In the past decade, numerous studies have revealed the presence and significance of PPARs in the reproductive system. PPARs are expressed at different levels of hypothalamic-pituitary-gonadal (HPG) axis. They are also present in the uterus as well as in the placenta and embryonic tissues of different species. PPARs significance has been reported during the estrous/menstrual cycle and pregnancy with the gamma isoform studied most frequently. Several studies indicate that PPARs regulate proliferation of ovarian cells, tissue remodeling and steroidogenesis. In the endometrium, PPARs are engaged in the regulation of prostaglandins, steroids and cytokines synthesis. The role of PPARs in the trophoblast differentiation, maturation and invasion as well as in the embryo development has also been demonstrated. In this review, we summarize current findings concerning the role of PPARs in the regulation of reproductive functions at different levels of the HPG axis during various physiological statuses of females. In addition, the role of PPARs in the modulation of uterine functions as well as the placenta and embryo development has also been discussed.
The European beaver (Castor fiber L.) is an important free-living rodent that inhabits Eurasian temperate forests. Beavers are often referred to as ecosystem engineers because they create or change existing habitats, enhance biodiversity and prepare the environment for diverse plant and animal species. Beavers are protected in most European Union countries, but their genomic background remains unknown. In this study, gene expression patterns in beaver testes and the variations in genetic expression in breeding and non-breeding seasons were determined by high-throughput transcriptome sequencing. Paired-end sequencing in the Illumina HiSeq 2000 sequencer produced a total of 373.06 million of high-quality reads. De novo assembly of contigs yielded 130,741 unigenes with an average length of 1,369.3 nt, N50 value of 1,734, and average GC content of 46.51%. A comprehensive analysis of the testicular transcriptome revealed more than 26,000 highly expressed unigenes which exhibited the highest homology with Rattus norvegicus and Ictidomys tridecemlineatus genomes. More than 8,000 highly expressed genes were found to be involved in fundamental biological processes, cellular components or molecular pathways. The study also revealed 42 genes whose regulation differed between breeding and non-breeding seasons. During the non-breeding period, the expression of 37 genes was up-regulated, and the expression of 5 genes was down-regulated relative to the breeding season. The identified genes encode molecules which are involved in signaling transduction, DNA repair, stress responses, inflammatory processes, metabolism and steroidogenesis. Our results pave the way for further research into season-dependent variations in beaver testes.
Problem
Cytokines, mediators of the immune response, are involved in the regulation of female reproductive processes during the estrous cycle and pregnancy. The present study aimed to investigate the effect of selected peroxisome proliferator‐activated receptor gamma (PPARγ) ligands on the expression of nuclear factor kappa B (NF‐κB) and selected cytokines, such as interleukin (IL)‐1β, ‐4, ‐6, ‐8, ‐10, and the leukemia inhibitory factor, in the porcine endometrium on days 10‐12 and 14‐16 of the estrous cycle (mid‐ and late luteal phase, respectively) or pregnancy (maternal recognition of pregnancy and beginning of implantation, respectively).
Method of study
Endometrial slices were incubated in vitro in the presence of PPARγ agonists, 15‐deoxy‐Δ12, 14‐prostaglandin J2 or rosiglitazone, and PPARγ antagonist T0070907. mRNA and protein levels in tissues were determined by real‐time PCR and Western blot.
Results
On days 10‐12 of the estrous cycle and days 14‐16 of pregnancy, PPARγ ligands enhanced the expression of NF‐κB, mRNA cytokines, and/or proteins. During the late luteal phase of the estrous cycle (days 14‐16) and maternal recognition of pregnancy (days 10‐12), PPARγ ligands inhibited the expression of NF‐κB, and they differentially affected the expression of mRNA and proteins of cytokines.
Conclusion
Our results indicate that PPARγ is engaged in the endometrial synthesis of NF‐κB and selected cytokines in pigs. The influence of PPARγ ligands on the tested components of the immune system varied subject to the physiological status of females, and it could be associated with differences in endometrial receptivity.
AbstrAct:In the present study, we investigated the effect of PPAR ligands on progesterone (P 4 ) and 17β-estradiol (E 2 ) secretion, as well as 3β-hydroxysteroid dehydrogenase/Δ(5)-Δ(4) isomerase (3β-HSD) mRNA expression, in porcine endometrial slices collected on days 10-12 and 14-16 of the estrous cycle or early pregnancy. The explants were incubated in vitro for 6 h in the presence of PPARα ligands -WY-14643 (agonist) and MK 886 (antagonist); PPARβ ligands -L-165041 (agonist) and GW 9662 (antagonist); PPARγ ligands -15d-prostaglandin J 2 and rosiglitazone (agonists) and T0070907 (antagonist). During the estrous cycle, all PPAR ligands inhibited P 4 secretion during the mid-luteal phase (days 10-12). During early pregnancy, a stimulatory effect of PPARα agonist was observed during maternal recognition of pregnancy (days 10-12), while an inhibitory effect was observed at the beginning of implantation (days 14-16). PPAR ligands inhibited the expression of 3β-HSD mRNA on days 14-16 of the estrous cycle (β and γ isoforms) or pregnancy (α, β, γ isoforms) but did not affect gene expression on days 10-12 of the estrous cycle or early pregnancy. An inhibitory effect of PPARα, PPARγ, and PPARβ on E 2 secretion was observed during maternal recognition of pregnancy, but a stimulatory effect was observed during mid-(γ isoform) or late-luteal (β isoform) phases of the estrous cycle. Our study indicates, for the first time, that PPARs are engaged in P 4 and E 2 production in porcine endometrium. It is possible that the diverse receptivity of endometrial tissue to the PPAR ligands can be associated with the reproductive status of gilts.
Female fertility depends greatly on the capacity of the uterus to recognize and eliminate microbial infections, a major reason of inflammation in the endometrium in many species. This study aimed to determine the in vitro effect of PPARγ ligands on the transcriptome genes expression and alternative splicing in the porcine endometrium in the mid-luteal phase during LPS-stimulated inflammation using RNA-seq technology. The endometrial slices were incubated in vitro in the presence of LPS and PPARγ agonists—PGJ2 or pioglitazone and antagonist—T0070907. We identified 222, 3, 4 and 62 differentially expressed genes after LPS, PGJ2, pioglitazone or T0070907 treatment, respectively. In addition, we detected differentially alternative spliced events: after treatment with LPS—78, PGJ2–60, pioglitazone—52 or T0070907–134. These results should become a basis for further studies explaining the mechanism of PPARγ action in the reproductive system in pigs.
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