Critical role of mTOR, PPARγ and PPARδ signaling in regulating early pregnancy decidual function, embryo viability and feto-placental growth

Roberti, Sabrina Lorena; Higa, Romina; White, Verónica; Powell, Theresa L.; Jansson, Thomas; Jawerbaum, Alicia

doi:10.1093/molehr/gay013

Cited by 31 publications

(20 citation statements)

References 59 publications

(97 reference statements)

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“…PPARγ, a downstream regulator of FPR2, is a member of nuclear receptor transcription factor superfamily and is involved in a variety of physiological and pathological processes such as lipid and glucose metabolism, energy homeostasis, inflammation, cell proliferation and differentiation. The previous study revealed that PPARγ was involved in the invasion and differentiation of trophoblasts 41 and played an important role in embryo implantation, placenta formation and trophoblast differentiation and maturation. PPARγ can also inhibit inflammation by entering the nucleus, following binding to NF‐κBp65 and inhibiting its transcriptional activity 42 .…”

Section: Discussionmentioning

confidence: 99%

Effect of RvD1/FPR2 on inflammatory response in chorioamnionitis

Zhang

et al. 2020

J Cellular Molecular Medi

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Chorioamnionitis (CAM), as a common intrauterine infectious disease, is the leading cause of premature birth, stillbirth, neonatal infection and sepsis. The formyl peptide receptor 2 (FPR2) is a member of GPCRs widely distributed in a variety of tissues and is associated with many inflammatory diseases. With the discovery of FPR2 in human placenta, the possibility of exploring the function of FPR2 in obstetrics is evolving. The Resolvin D1 (RvD1) plays an important role in the resolution of inflammation by combining with FPR2. In this study, we evaluated the role of FPR2 and RvD1 in CAM, not only in the human placenta but also in mouse models. The expression of FPR2 increased in the placenta of CAM patients and the downstream PPARγ/NF‐κB signalling changed accordingly. Moreover, Fpr2−/− mice were highly susceptible to LPS, displaying a worse CAM symptom, compared with WT mice. By establishing a model of trophoblast inflammation in vitro, it was confirmed that RvD1 rescued the effect of LPS on inflammation by combining with FPR2 and its downstream PPARγ/NF‐κB pathway. Otherwise, RvD1 improved the preterm labour in a mouse model of CAM induced by LPS. Altogether, these findings show that RvD1 alleviated the inflammation of trophoblast in vivo and in vitro through FPR2/PPARγ/NF‐κB pathway, suggesting RvD1/FPR2 might be a novel therapeutic strategy to alleviate CAM.

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Section: Discussionmentioning

confidence: 99%

Effect of RvD1/FPR2 on inflammatory response in chorioamnionitis

Zhang

et al. 2020

J Cellular Molecular Medi

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“…The presence of PPARδ and its role during the peri-implantation period was also documented in the ovine trophoblast [ 32 ]. In addition, Roberti et al [ 33 ] suggested that PPARδ was the key factor in post-implantation development, preventing embryo resorption. Taking the above into consideration, the presence of PPARs seems to be essential during bovine embryo development, but mechanisms of their regulatory function need to be proven in further studies.…”

Section: Discussionmentioning

confidence: 99%

mRNA Expression and Role of PPARγ and PPARδ in Bovine Preimplantation Embryos Depending on the Quality and Developmental Stage

Suwik

Sinderewicz

Boruszewska

et al. 2020

Animals

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Peroxisome proliferator-activated receptors (PPARs), a nuclear receptors for prostacyclin (PGI2) have been recognized as being essential for early embryo development. The objectives of the present study were to determine if the bovine early- and late-cleaved embryos in different stages of early development express PPARγ and PPARδ. Since embryo developmental competence depends on numerous biological factors, we evaluated if the expression of PPARγ and PPARδ correlate with selected embryo quality markers (SOX2, OCT4, PLAC8, IGF1R) in the in vitro produced embryos at different stages of their development. Developmental rates and embryo quality for early- and late-cleaved embryos were provided according to International Embryo Transfer Society (IETS; developmental stages: 2-, 4-, 16-cell embryo, morula, blastocyst (1—early, 2—developing, 3—expanded, 4—hatched); quality stages: A—high quality, B—moderate quality, C—low quality). We found that bovine embryos expressed mRNA of PPARδ and PPARγ at all stages of early development, independently of their quality. In addition, the expression of PPARδ and PPARγ correlated with the expression of quality markers in bovine blastocysts. Positive correlations were stronger and more frequent in the group of early-cleaved embryos, whereas the negative correlations were typical for the group of late-cleaved embryos. Obtained results and available literature reports may indicate the participation of PGI2, via PPARδ and PPARγ, in the processes related to the early embryo development, through the participation of this factor in the modulation of blastocyst hatching, implantation, and post-implantation development.

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“…To perform immunostaining for CTGF and MMP2, placental tissues were fixed in buffered formaldehyde solution 4% v/v, then paraffinized and serially cut into 5 μm thick sections. Then, as previously, sections were deparaffinized, rehydrated through a graded series of ethanol and the endogenous peroxidase activity was blocked. The sections were processed using the corresponding primary antibodies: anti‐CTGF (goat polyclonal antibody, 1:300 dilution, Santa Cruz Biotechnology), and anti‐MMP2 (mouse polyclonal antibody, 1:200 dilution, Santa Cruz Biotechnology).…”

Section: Methodsmentioning

confidence: 99%

Diet Enriched with Olive Oil Attenuates Placental Dysfunction in Rats with Gestational Diabetes Induced by Intrauterine Programming

Capobianco

Ribot

Fornes

et al. 2018

Molecular Nutrition Food Res

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Critical role of mTOR, PPARγ and PPARδ signaling in regulating early pregnancy decidual function, embryo viability and feto-placental growth

Abstract: Funding was provided by the Agencia Nacional de Promoción Científica y Tecnológica de Argentina (PICT 2014-411 and PICT 2015-0130), and by the International Cooperation (Grants CONICET-NIH-2014 and CONICET-NIH-2017) to A.J. and T.J. The authors have no conflicts of interest.

Cited by 31 publications

References 59 publications

Effect of RvD1/FPR2 on inflammatory response in chorioamnionitis

Effect of RvD1/FPR2 on inflammatory response in chorioamnionitis

mRNA Expression and Role of PPARγ and PPARδ in Bovine Preimplantation Embryos Depending on the Quality and Developmental Stage

Diet Enriched with Olive Oil Attenuates Placental Dysfunction in Rats with Gestational Diabetes Induced by Intrauterine Programming

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