Candesartan Does Not Activate PPARγ and Its Target Genes in Early Gestation Trophoblasts
Angiotensin II receptor 1 blockers are commonly used to treat hypertension in women of childbearing age. While the fetotoxic effects of these drugs in the second and third trimesters of pregnancy are well documented, their possible impacts on placenta development in early gestation are unknown. Cand...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-10-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/20/12326 |
| _version_ | 1797440881790287872 |
|---|---|
| author | Lena Neuper Daniel Kummer Désirée Forstner Jacqueline Guettler Nassim Ghaffari-Tabrizi-Wizsy Cornelius Fischer Herbert Juch Olivia Nonn Martin Gauster |
| author_facet | Lena Neuper Daniel Kummer Désirée Forstner Jacqueline Guettler Nassim Ghaffari-Tabrizi-Wizsy Cornelius Fischer Herbert Juch Olivia Nonn Martin Gauster |
| author_sort | Lena Neuper |
| collection | DOAJ |
| description | Angiotensin II receptor 1 blockers are commonly used to treat hypertension in women of childbearing age. While the fetotoxic effects of these drugs in the second and third trimesters of pregnancy are well documented, their possible impacts on placenta development in early gestation are unknown. Candesartan, a member of this group, also acts as a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, a key regulator shown to be important for placental development. We have previously shown that trophoblasts do not express the candesartan target–receptor angiotensin II type 1 receptor AGTR1. This study investigated the possible role of candesartan on trophoblastic PPARγ and its hallmark target genes in early gestation. Candesartan did not affect the PPARγ protein expression or nuclear translocation of PPARγ. To mimic extravillous trophoblasts (EVTs) and cytotrophoblast/syncytiotrophoblast (CTB/SCT) responses to candesartan, we used trophoblast cell models BeWo (for CTB/SCT) and SGHPL-4 (EVT) cells as well as placental explants. In vitro, the RT-qPCR analysis showed no effect of candesartan treatment on PPARγ target genes in BeWo or SGHPL-4 cells. Treatment with positive control rosiglitazone, another PPARγ agonist, led to decreased expressions of <i>LEP</i> and <i>PPARG1</i> in BeWo cells and an increased expression of PPARG1 in SGHPL-4 cells. Our previous data showed early gestation–placental AGTR1 expression in fetal myofibroblasts only. In a CAM assay, AGTR1 was stimulated with angiotensin II and showed increased on-plant vessel outgrowth. These results suggest candesartan does not negatively affect PPARγ or its target genes in human trophoblasts. More likely, candesartan from maternal serum may first act on fetal-placental AGTR1 and influence angiogenesis in the placenta, warranting further research. |
| first_indexed | 2024-03-09T12:15:49Z |
| format | Article |
| id | doaj.art-66f4dbf553af4fbba226ad55b5892dc3 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T12:15:49Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-66f4dbf553af4fbba226ad55b5892dc32023-11-30T22:47:13ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123201232610.3390/ijms232012326Candesartan Does Not Activate PPARγ and Its Target Genes in Early Gestation TrophoblastsLena Neuper0Daniel Kummer1Désirée Forstner2Jacqueline Guettler3Nassim Ghaffari-Tabrizi-Wizsy4Cornelius Fischer5Herbert Juch6Olivia Nonn7Martin Gauster8Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, 8010 Graz, AustriaDivision of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, 8010 Graz, AustriaDivision of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, 8010 Graz, AustriaDivision of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, 8010 Graz, AustriaDivision of Immunology, Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of Graz, 8010 Graz, AustriaInstitute for Medical Systems Biology (BIMSB), 10115 Berlin, GermanyDivision of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, 8010 Graz, AustriaDivision of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, 8010 Graz, AustriaDivision of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, 8010 Graz, AustriaAngiotensin II receptor 1 blockers are commonly used to treat hypertension in women of childbearing age. While the fetotoxic effects of these drugs in the second and third trimesters of pregnancy are well documented, their possible impacts on placenta development in early gestation are unknown. Candesartan, a member of this group, also acts as a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, a key regulator shown to be important for placental development. We have previously shown that trophoblasts do not express the candesartan target–receptor angiotensin II type 1 receptor AGTR1. This study investigated the possible role of candesartan on trophoblastic PPARγ and its hallmark target genes in early gestation. Candesartan did not affect the PPARγ protein expression or nuclear translocation of PPARγ. To mimic extravillous trophoblasts (EVTs) and cytotrophoblast/syncytiotrophoblast (CTB/SCT) responses to candesartan, we used trophoblast cell models BeWo (for CTB/SCT) and SGHPL-4 (EVT) cells as well as placental explants. In vitro, the RT-qPCR analysis showed no effect of candesartan treatment on PPARγ target genes in BeWo or SGHPL-4 cells. Treatment with positive control rosiglitazone, another PPARγ agonist, led to decreased expressions of <i>LEP</i> and <i>PPARG1</i> in BeWo cells and an increased expression of PPARG1 in SGHPL-4 cells. Our previous data showed early gestation–placental AGTR1 expression in fetal myofibroblasts only. In a CAM assay, AGTR1 was stimulated with angiotensin II and showed increased on-plant vessel outgrowth. These results suggest candesartan does not negatively affect PPARγ or its target genes in human trophoblasts. More likely, candesartan from maternal serum may first act on fetal-placental AGTR1 and influence angiogenesis in the placenta, warranting further research.https://www.mdpi.com/1422-0067/23/20/12326candesartanPPARγplacentatrophoblastfirst-trimester pregnancyrosiglitazone |
| spellingShingle | Lena Neuper Daniel Kummer Désirée Forstner Jacqueline Guettler Nassim Ghaffari-Tabrizi-Wizsy Cornelius Fischer Herbert Juch Olivia Nonn Martin Gauster Candesartan Does Not Activate PPARγ and Its Target Genes in Early Gestation Trophoblasts International Journal of Molecular Sciences candesartan PPARγ placenta trophoblast first-trimester pregnancy rosiglitazone |
| title | Candesartan Does Not Activate PPARγ and Its Target Genes in Early Gestation Trophoblasts |
| title_full | Candesartan Does Not Activate PPARγ and Its Target Genes in Early Gestation Trophoblasts |
| title_fullStr | Candesartan Does Not Activate PPARγ and Its Target Genes in Early Gestation Trophoblasts |
| title_full_unstemmed | Candesartan Does Not Activate PPARγ and Its Target Genes in Early Gestation Trophoblasts |
| title_short | Candesartan Does Not Activate PPARγ and Its Target Genes in Early Gestation Trophoblasts |
| title_sort | candesartan does not activate pparγ and its target genes in early gestation trophoblasts |
| topic | candesartan PPARγ placenta trophoblast first-trimester pregnancy rosiglitazone |
| url | https://www.mdpi.com/1422-0067/23/20/12326 |
| work_keys_str_mv | AT lenaneuper candesartandoesnotactivatepparganditstargetgenesinearlygestationtrophoblasts AT danielkummer candesartandoesnotactivatepparganditstargetgenesinearlygestationtrophoblasts AT desireeforstner candesartandoesnotactivatepparganditstargetgenesinearlygestationtrophoblasts AT jacquelineguettler candesartandoesnotactivatepparganditstargetgenesinearlygestationtrophoblasts AT nassimghaffaritabriziwizsy candesartandoesnotactivatepparganditstargetgenesinearlygestationtrophoblasts AT corneliusfischer candesartandoesnotactivatepparganditstargetgenesinearlygestationtrophoblasts AT herbertjuch candesartandoesnotactivatepparganditstargetgenesinearlygestationtrophoblasts AT olivianonn candesartandoesnotactivatepparganditstargetgenesinearlygestationtrophoblasts AT martingauster candesartandoesnotactivatepparganditstargetgenesinearlygestationtrophoblasts |