Maternal Nodal inversely affects NODAL and STOX1 expression in the fetal placenta
Nodal, a secreted signaling protein from the TGFβ-super family plays a vital role during early embryonic development. Recently, it was found that maternal decidua-specific Nodal knockout mice show intrauterine growth restriction (IUGR) and preterm birth. As the chromosomal location of NODAL is in th...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2013-08-01
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| Series: | Frontiers in Genetics |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fgene.2013.00170/full |
| _version_ | 1818037797184864256 |
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| author | Hari Krishna Thulluru Craig ePark Daniel eDufort Gunilla eKleiverda Cees eOudejans Marie eVan Dijk |
| author_facet | Hari Krishna Thulluru Craig ePark Daniel eDufort Gunilla eKleiverda Cees eOudejans Marie eVan Dijk |
| author_sort | Hari Krishna Thulluru |
| collection | DOAJ |
| description | Nodal, a secreted signaling protein from the TGFβ-super family plays a vital role during early embryonic development. Recently, it was found that maternal decidua-specific Nodal knockout mice show intrauterine growth restriction (IUGR) and preterm birth. As the chromosomal location of NODAL is in the same linkage area as the susceptibility gene STOX1, associated with the familial form of early-onset, IUGR-complicated pre-eclampsia, their potential maternal-fetal interaction was investigated. Pre-eclamptic mothers with children who carried the STOX1 susceptibility allele themselves all carried the NODAL H165R SNP, which causes a 50% reduced activity. Surprisingly, in decidua Nodal knockout mice the fetal placenta showed up-regulation of STOX1 and NODAL expression. Conditioned media of human first trimester decidua and a human endometrial stromal cell line (T-HESC) treated with siRNAs against NODAL or carrying the H165R SNP were also able to induce NODAL and STOX1 expression when added to SGHPL-5 first trimester extravillous trophoblast cells. Finally, a human TGFß-BMP-Signaling-Pathway PCR-Array on decidua and the T-HESC cell line with Nodal knockdown revealed upregulation of Activin-A, which was confirmed in conditioned media by ELISA. We show that maternal decidua Nodal knockdown gives upregulation of NODAL and STOX1 mRNA expression in fetal extravillous trophoblast cells, potentially via upregulation of Activin-A in the maternal decidua. As both Activin-A and Nodal have been implicated in pre-eclampsia, being increased in serum of pre-eclamptic women and upregulated in pre-eclamptic placentas respectively, this interaction at the maternal-fetal interface might play a substantial role in the development of pre-eclampsia. |
| first_indexed | 2024-12-10T07:32:33Z |
| format | Article |
| id | doaj.art-2189a0d7054548c1a28b3749e48963fa |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-10T07:32:33Z |
| publishDate | 2013-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-2189a0d7054548c1a28b3749e48963fa2022-12-22T01:57:31ZengFrontiers Media S.A.Frontiers in Genetics1664-80212013-08-01410.3389/fgene.2013.0017060317Maternal Nodal inversely affects NODAL and STOX1 expression in the fetal placentaHari Krishna Thulluru0Craig ePark1Daniel eDufort2Gunilla eKleiverda3Cees eOudejans4Marie eVan Dijk5VU University Medical CenterMcGill University Health CentreMcGill University Health CentreFlevoziekenhuisVU University Medical CenterVU University Medical CenterNodal, a secreted signaling protein from the TGFβ-super family plays a vital role during early embryonic development. Recently, it was found that maternal decidua-specific Nodal knockout mice show intrauterine growth restriction (IUGR) and preterm birth. As the chromosomal location of NODAL is in the same linkage area as the susceptibility gene STOX1, associated with the familial form of early-onset, IUGR-complicated pre-eclampsia, their potential maternal-fetal interaction was investigated. Pre-eclamptic mothers with children who carried the STOX1 susceptibility allele themselves all carried the NODAL H165R SNP, which causes a 50% reduced activity. Surprisingly, in decidua Nodal knockout mice the fetal placenta showed up-regulation of STOX1 and NODAL expression. Conditioned media of human first trimester decidua and a human endometrial stromal cell line (T-HESC) treated with siRNAs against NODAL or carrying the H165R SNP were also able to induce NODAL and STOX1 expression when added to SGHPL-5 first trimester extravillous trophoblast cells. Finally, a human TGFß-BMP-Signaling-Pathway PCR-Array on decidua and the T-HESC cell line with Nodal knockdown revealed upregulation of Activin-A, which was confirmed in conditioned media by ELISA. We show that maternal decidua Nodal knockdown gives upregulation of NODAL and STOX1 mRNA expression in fetal extravillous trophoblast cells, potentially via upregulation of Activin-A in the maternal decidua. As both Activin-A and Nodal have been implicated in pre-eclampsia, being increased in serum of pre-eclamptic women and upregulated in pre-eclamptic placentas respectively, this interaction at the maternal-fetal interface might play a substantial role in the development of pre-eclampsia.http://journal.frontiersin.org/Journal/10.3389/fgene.2013.00170/fullDeciduaPre-EclampsiaNodalextravillous trophoblastSTOX1 |
| spellingShingle | Hari Krishna Thulluru Craig ePark Daniel eDufort Gunilla eKleiverda Cees eOudejans Marie eVan Dijk Maternal Nodal inversely affects NODAL and STOX1 expression in the fetal placenta Frontiers in Genetics Decidua Pre-Eclampsia Nodal extravillous trophoblast STOX1 |
| title | Maternal Nodal inversely affects NODAL and STOX1 expression in the fetal placenta |
| title_full | Maternal Nodal inversely affects NODAL and STOX1 expression in the fetal placenta |
| title_fullStr | Maternal Nodal inversely affects NODAL and STOX1 expression in the fetal placenta |
| title_full_unstemmed | Maternal Nodal inversely affects NODAL and STOX1 expression in the fetal placenta |
| title_short | Maternal Nodal inversely affects NODAL and STOX1 expression in the fetal placenta |
| title_sort | maternal nodal inversely affects nodal and stox1 expression in the fetal placenta |
| topic | Decidua Pre-Eclampsia Nodal extravillous trophoblast STOX1 |
| url | http://journal.frontiersin.org/Journal/10.3389/fgene.2013.00170/full |
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