Heme Oxygenase-1 is critically involved in placentation, spiral artery remodeling and blood pressure regulation during murine pregnancy
The onset of pregnancy implies the appearance of a new organ, the placenta. One main function of the placenta is to supply oxygen to the fetus via hemoproteins. In this review, we highlight the importance of the enzyme heme oxygenase-1 (HO-1) for pregnancy to be established and maintained. HO-1 expr...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphar.2014.00291/full |
| _version_ | 1818056857027084288 |
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| author | Maria Laura Zenclussen Nadja eLinzke Anne eSchumacher Stefan eFest Nicole eMeyer Pablo Ariel Casalis Ana Claudia Zenclussen |
| author_facet | Maria Laura Zenclussen Nadja eLinzke Anne eSchumacher Stefan eFest Nicole eMeyer Pablo Ariel Casalis Ana Claudia Zenclussen |
| author_sort | Maria Laura Zenclussen |
| collection | DOAJ |
| description | The onset of pregnancy implies the appearance of a new organ, the placenta. One main function of the placenta is to supply oxygen to the fetus via hemoproteins. In this review, we highlight the importance of the enzyme heme oxygenase-1 (HO-1) for pregnancy to be established and maintained. HO-1 expression is pivotal to promote placental function and fetal development, thus determining the success of pregnancy. The deletion of the gene Hmox1 in mice leads to inadequate remodeling of spiral arteries and suboptimal placentation followed by intrauterine growth restriction (IUGR) and fetal lethality. A partial Hmox1 deletion leads to IUGR as well, with heterozygote and wild-type fetuses being born, but Hmox1-/- significantly below the expected Mendelian rate. This strong phenotype is associated with diminished number of pregnancy-protective uterine natural killer (uNK) cells. Pregnant heterozygote females develop gestational hypertension. The protective HO-1 effects on placentation and fetal growth can be mimicked by the exogenous administration of carbon monoxide (CO), a product of heme catalyzed by HO-1. CO application promotes the in situ proliferation of uNK cells, restores placentation and fetal growth, while normalizing blood pressure. Similarly, HO-1 inhibition provokes hypertension in pregnant rats. The HO-1/CO axis plays a pivotal role in sustaining pregnancy and aids in the understanding of the biology of pregnancy and reveals a promising therapeutic application in the treatment of pregnancy complications. |
| first_indexed | 2024-12-10T12:35:30Z |
| format | Article |
| id | doaj.art-ab5f34d8d0484115a768d894eb709e33 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-10T12:35:30Z |
| publishDate | 2015-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-ab5f34d8d0484115a768d894eb709e332022-12-22T01:48:41ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122015-01-01510.3389/fphar.2014.00291124262Heme Oxygenase-1 is critically involved in placentation, spiral artery remodeling and blood pressure regulation during murine pregnancyMaria Laura Zenclussen0Nadja eLinzke1Anne eSchumacher2Stefan eFest3Nicole eMeyer4Pablo Ariel Casalis5Ana Claudia Zenclussen6Medical Faculty, Otto-von-Guericke UniversityMedical Faculty, Otto-von-Guericke UniversityMedical Faculty, Otto-von-Guericke UniversityMedical Faculty, Otto-von-Guericke UniversityMedical Faculty, Otto-von-Guericke UniversityMedical Faculty, Otto-von-Guericke UniversityMedical Faculty, Otto-von-Guericke UniversityThe onset of pregnancy implies the appearance of a new organ, the placenta. One main function of the placenta is to supply oxygen to the fetus via hemoproteins. In this review, we highlight the importance of the enzyme heme oxygenase-1 (HO-1) for pregnancy to be established and maintained. HO-1 expression is pivotal to promote placental function and fetal development, thus determining the success of pregnancy. The deletion of the gene Hmox1 in mice leads to inadequate remodeling of spiral arteries and suboptimal placentation followed by intrauterine growth restriction (IUGR) and fetal lethality. A partial Hmox1 deletion leads to IUGR as well, with heterozygote and wild-type fetuses being born, but Hmox1-/- significantly below the expected Mendelian rate. This strong phenotype is associated with diminished number of pregnancy-protective uterine natural killer (uNK) cells. Pregnant heterozygote females develop gestational hypertension. The protective HO-1 effects on placentation and fetal growth can be mimicked by the exogenous administration of carbon monoxide (CO), a product of heme catalyzed by HO-1. CO application promotes the in situ proliferation of uNK cells, restores placentation and fetal growth, while normalizing blood pressure. Similarly, HO-1 inhibition provokes hypertension in pregnant rats. The HO-1/CO axis plays a pivotal role in sustaining pregnancy and aids in the understanding of the biology of pregnancy and reveals a promising therapeutic application in the treatment of pregnancy complications.http://journal.frontiersin.org/Journal/10.3389/fphar.2014.00291/fullHeme Oxygenase-1PlacentaPre-EclampsiaPregnancyimplantationIUGR |
| spellingShingle | Maria Laura Zenclussen Nadja eLinzke Anne eSchumacher Stefan eFest Nicole eMeyer Pablo Ariel Casalis Ana Claudia Zenclussen Heme Oxygenase-1 is critically involved in placentation, spiral artery remodeling and blood pressure regulation during murine pregnancy Frontiers in Pharmacology Heme Oxygenase-1 Placenta Pre-Eclampsia Pregnancy implantation IUGR |
| title | Heme Oxygenase-1 is critically involved in placentation, spiral artery remodeling and blood pressure regulation during murine pregnancy |
| title_full | Heme Oxygenase-1 is critically involved in placentation, spiral artery remodeling and blood pressure regulation during murine pregnancy |
| title_fullStr | Heme Oxygenase-1 is critically involved in placentation, spiral artery remodeling and blood pressure regulation during murine pregnancy |
| title_full_unstemmed | Heme Oxygenase-1 is critically involved in placentation, spiral artery remodeling and blood pressure regulation during murine pregnancy |
| title_short | Heme Oxygenase-1 is critically involved in placentation, spiral artery remodeling and blood pressure regulation during murine pregnancy |
| title_sort | heme oxygenase 1 is critically involved in placentation spiral artery remodeling and blood pressure regulation during murine pregnancy |
| topic | Heme Oxygenase-1 Placenta Pre-Eclampsia Pregnancy implantation IUGR |
| url | http://journal.frontiersin.org/Journal/10.3389/fphar.2014.00291/full |
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