Folic Acid Levels During Pregnancy Regulate Trophoblast Invasive Behavior and the Possible Development of Preeclampsia
BackgroundOne of the unique features of placentation is its similarity to tumorigenesis yet being very well regulated. It allows rapid proliferation, migration, and invasion of mononuclear trophoblast cells into the maternal uterus and remodeling the maternal vasculature. This pseudomalignant nature...
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| Format: | Article |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Nutrition |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnut.2022.847136/full |
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| author | Beenish Rahat Abid Hamid Rashmi Bagga Jyotdeep Kaur |
| author_facet | Beenish Rahat Abid Hamid Rashmi Bagga Jyotdeep Kaur |
| author_sort | Beenish Rahat |
| collection | DOAJ |
| description | BackgroundOne of the unique features of placentation is its similarity to tumorigenesis yet being very well regulated. It allows rapid proliferation, migration, and invasion of mononuclear trophoblast cells into the maternal uterus and remodeling the maternal vasculature. This pseudomalignant nature of trophoblastic cells is strictly regulated and its importance becomes evident in abnormal pregnancies that are characterized by aberrant trophoblast proliferation/invasion like preeclampsia. In addition to this, the importance of folic acid supplementation during pregnancy is well documented. We aimed to analyze the molecular and epigenetic regulation of the pseudomalignant nature of placentation via folic acid levels.MethodsPlacental tissue samples were collected from different pregnancies in three different gestational stages. We estimated the impact of folic acid levels on global methylation, LINE1 methylation, and expression of DNMTs in all three gestational stages in pregnant women and preeclampsia pregnancies. We also analyzed the effect of folic acid supplementation on trophoblastic invasion using placental derived cells viz, JEG-3 and HTR-8/SVneo cell line and verified the molecular and epigenetic mechanisms involved in this regulation.ResultsDevelopment of preeclampsia was observed to be associated with lower folate levels in placental tissue, higher global methylation level, and higher expression of DNMT1and DNMT3A. Folic acid supplementation was found to increase the invasive potential of placental trophoblasts by almost two folds which were associated with the decreased expression of tumor suppressor genes and tissue inhibitors of matrix metalloproteinases; and increased expression of oncogenes, telomerase gene, and matrix metalloproteinases. These folic acid-mediated changes were observed to be regulated by CpG methylation in the case of many genes. Folic acid supplementation was also observed to significantly decrease global methylation in placental trophoblasts related to decreasing expression of DNMT1 and DNMT3A.ConclusionLower folic acid levels are associated with preeclampsia development and folic acid supplementation regulates the invasive potential of placental trophoblasts as mediated by various epigenetic changes in the placenta suggesting the protective effect of folic acid against preeclampsia. |
| first_indexed | 2024-04-14T06:47:33Z |
| format | Article |
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| issn | 2296-861X |
| language | English |
| last_indexed | 2024-04-14T06:47:33Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Nutrition |
| spelling | doaj.art-534aa19574824e13bdabf970c1a2a6552022-12-22T02:07:08ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2022-04-01910.3389/fnut.2022.847136847136Folic Acid Levels During Pregnancy Regulate Trophoblast Invasive Behavior and the Possible Development of PreeclampsiaBeenish Rahat0Abid Hamid1Rashmi Bagga2Jyotdeep Kaur3Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, IndiaCancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, IndiaDepartment of Obstetrics and Gynecology, Postgraduate Institute of Medical Education and Research, Chandigarh, IndiaDepartment of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, IndiaBackgroundOne of the unique features of placentation is its similarity to tumorigenesis yet being very well regulated. It allows rapid proliferation, migration, and invasion of mononuclear trophoblast cells into the maternal uterus and remodeling the maternal vasculature. This pseudomalignant nature of trophoblastic cells is strictly regulated and its importance becomes evident in abnormal pregnancies that are characterized by aberrant trophoblast proliferation/invasion like preeclampsia. In addition to this, the importance of folic acid supplementation during pregnancy is well documented. We aimed to analyze the molecular and epigenetic regulation of the pseudomalignant nature of placentation via folic acid levels.MethodsPlacental tissue samples were collected from different pregnancies in three different gestational stages. We estimated the impact of folic acid levels on global methylation, LINE1 methylation, and expression of DNMTs in all three gestational stages in pregnant women and preeclampsia pregnancies. We also analyzed the effect of folic acid supplementation on trophoblastic invasion using placental derived cells viz, JEG-3 and HTR-8/SVneo cell line and verified the molecular and epigenetic mechanisms involved in this regulation.ResultsDevelopment of preeclampsia was observed to be associated with lower folate levels in placental tissue, higher global methylation level, and higher expression of DNMT1and DNMT3A. Folic acid supplementation was found to increase the invasive potential of placental trophoblasts by almost two folds which were associated with the decreased expression of tumor suppressor genes and tissue inhibitors of matrix metalloproteinases; and increased expression of oncogenes, telomerase gene, and matrix metalloproteinases. These folic acid-mediated changes were observed to be regulated by CpG methylation in the case of many genes. Folic acid supplementation was also observed to significantly decrease global methylation in placental trophoblasts related to decreasing expression of DNMT1 and DNMT3A.ConclusionLower folic acid levels are associated with preeclampsia development and folic acid supplementation regulates the invasive potential of placental trophoblasts as mediated by various epigenetic changes in the placenta suggesting the protective effect of folic acid against preeclampsia.https://www.frontiersin.org/articles/10.3389/fnut.2022.847136/fullfolate (folic acid)trophoblast invasionpreeclampsiapregnancyDNA methylationplacenta |
| spellingShingle | Beenish Rahat Abid Hamid Rashmi Bagga Jyotdeep Kaur Folic Acid Levels During Pregnancy Regulate Trophoblast Invasive Behavior and the Possible Development of Preeclampsia Frontiers in Nutrition folate (folic acid) trophoblast invasion preeclampsia pregnancy DNA methylation placenta |
| title | Folic Acid Levels During Pregnancy Regulate Trophoblast Invasive Behavior and the Possible Development of Preeclampsia |
| title_full | Folic Acid Levels During Pregnancy Regulate Trophoblast Invasive Behavior and the Possible Development of Preeclampsia |
| title_fullStr | Folic Acid Levels During Pregnancy Regulate Trophoblast Invasive Behavior and the Possible Development of Preeclampsia |
| title_full_unstemmed | Folic Acid Levels During Pregnancy Regulate Trophoblast Invasive Behavior and the Possible Development of Preeclampsia |
| title_short | Folic Acid Levels During Pregnancy Regulate Trophoblast Invasive Behavior and the Possible Development of Preeclampsia |
| title_sort | folic acid levels during pregnancy regulate trophoblast invasive behavior and the possible development of preeclampsia |
| topic | folate (folic acid) trophoblast invasion preeclampsia pregnancy DNA methylation placenta |
| url | https://www.frontiersin.org/articles/10.3389/fnut.2022.847136/full |
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