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Pregnancy-associated changes of peroxisome proliferator-activated receptor delta (PPARD) and cytochrome P450 family 21 subfamily A member 2 (CYP21A2) expression in the bovine corpus luteum.

ABSTRACT: We investigated gene expression profiles of the corpus luteum (CL) at the time of maternal recognition to evaluate the functional changes of the CL during early pregnancy in cows and help improve reproductive efficiency and avoid defective fetuses. Microarray analyses using a 15 K bovine oligo DNA microarray detected 30 differentially expressed genes and 266 differentially expressed genes (e.g., PPARD and CYP21A2) in the CL on pregnancy days 15 (P15) and 18 (P18), respectively, compared with the CL on day 15 (NP15) of non-pregnancy (n = 4 for each group). PPARD expression was the highest while the CYP21A2 expression was the lowest in P15 and P18 compared with that of NP15. These microarray results were validated by quantitative real-time PCR analysis. The addition of interferon-? and supernatants derived from homogenized fetal trophoblast increased ISG15 and MX1 expressions in the cultured luteal tissue (P < 0.01), but did not affect PPARD and CYP21A2 expressions. PPARD expression in the luteal tissue was stimulated (P < 0.05) by GW0742, known as a selective PPARD agonist, and PPARD ligands (i.e., arachidonic, linoleic and linolenic acids). In contrast, CYP21A2 mRNA expression was not affected by both agonist and ligands. The concentration of prostaglandin (PG) E2 and PGF2? decreased after GW0742 stimulation and increased after arachidonic acid stimulation (P < 0.05). The addition of GW0742 and arachidonic acid increased progesterone (P4) concentration. Collectively, these findings suggest that high expression levels of PPARD and low expression levels of CYP21A2 in the CL during early pregnancy may support P4 production by bovine luteal cells.

SUBMITTER: Sakumoto R

PROVIDER: S-EPMC7297635 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Pregnancy-associated changes of peroxisome proliferator-activated receptor delta (PPARD) and cytochrome P450 family 21 subfamily A member 2 (CYP21A2) expression in the bovine corpus luteum.

Sakumoto Ryosuke R Hayashi Ken-Go KG Hosoe Misa M Iga Kosuke K Kizaki Keiichiro K

The Journal of reproduction and development 20200207 3

We investigated gene expression profiles of the corpus luteum (CL) at the time of maternal recognition to evaluate the functional changes of the CL during early pregnancy in cows and help improve reproductive efficiency and avoid defective fetuses. Microarray analyses using a 15 K bovine oligo DNA microarray detected 30 differentially expressed genes and 266 differentially expressed genes (e.g., PPARD and CYP21A2) in the CL on pregnancy days 15 (P15) and 18 (P18), respectively, compared with the ...[more]

PMID: 32037375

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Project description:Simple Summary The corpus luteum (CL) is responsible for progesterone (P4) secretion. In the absence of pregnancy, luteolysis occurs, which leads to a reduction in P4 production, followed by the structural regression of the CL. In cows, prostaglandin F2α (PGF2α) 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., PPARα, PPARδ and PPARγ, 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 PGF2α-induced processes related to luteolysis. The obtained results indicate that the expression of PPARs changes in the bovine CL throughout the estrous cycle; moreover, PGF2α affects its expression. This study provides evidence that PPARγ, among all examined PPAR isoforms, could be involved in the regulation of PGF2α-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. Abstract 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 PPARα, PPARδ and PPARγ in the bovine corpus luteum (CL) (n = 40) throughout the estrous cycle, and (ii) the involvement of PPAR in PGF2α-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 PGF2α receptor antagonist (10−5 M) and PGF2α (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. PGF2α upregulated PPARδ and PPARγ mRNA expression in the bovine CL in vitro, whereas PPARγ increased the inhibitory effect of PGF2α by decreasing progesterone secretion and the mRNA expression of hydroxy-delta-5-steroid dehydrogenase, 3 β- and steroid delta-isomerase 1 (HSD3B1) in the CL explants; mRNA transcription of tumor necrosis factor α (TNFα) 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 PGF2α. We suggest that isoform γ, among all examined PPARs, could be a factor involved in the regulation of PGF2α-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.

Project description:BackgroundDespite significant advances in our understanding of the pathophysiology of preeclampsia (PE), there are still many unknowns and controversies in the field. Women undergoing frozen-thawed embryo transfer (FET) to a hormonally prepared endometrium have been found to have an unexpected increased risk of PE compared to women who receive embryos in a natural FET cycle. The differences in risk have been hypothesized to be related to the absence or presence of a functioning corpus luteum (CL).Objective and rationaleTo evaluate the literature on secretory products of the CL that could be essential for a healthy pregnancy and could reduce the risk of PE in the setting of FET.Search methodsFor this review, pertinent studies were searched in PubMed/Medline (updated June 2020) using common keywords applied in the field of assisted reproductive technologies, CL physiology and preeclampsia. We also screened the complete list of references in recent publications in English (both animal and human studies) on the topics investigated. Given the design of this work as a narrative review, no formal criteria for study selection or appraisal were utilized.OutcomesThe CL is a major source of multiple factors regulating reproduction. Progesterone, estradiol, relaxin and vasoactive and angiogenic substances produced by the CL have important roles in regulating its functional lifespan and are also secreted into the circulation to act remotely during early stages of pregnancy. Beyond the known actions of progesterone and estradiol on the uterus in early pregnancy, their metabolites have angiogenic properties that may optimize implantation and placentation. Serum levels of relaxin are almost undetectable in pregnant women without a CL, which precludes some maternal cardiovascular and renal adaptations to early pregnancy. We suggest that an imbalance in steroid hormones and their metabolites and polypeptides influencing early physiologic processes such as decidualization, implantation, angiogenesis and maternal haemodynamics could contribute to the increased PE risk among women undergoing programmed FET cycles.Wider implicationsA better understanding of the critical roles of the secretory products of the CL during early pregnancy holds the promise of improving the efficacy and safety of ART based on programmed FET cycles.

Dataset Information

Pregnancy-associated changes of peroxisome proliferator-activated receptor delta (PPARD) and cytochrome P450 family 21 subfamily A member 2 (CYP21A2) expression in the bovine corpus luteum.

Publications

Pregnancy-associated changes of peroxisome proliferator-activated receptor delta (PPARD) and cytochrome P450 family 21 subfamily A member 2 (CYP21A2) expression in the bovine corpus luteum.

Similar Datasets

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