دورية أكاديمية
Placental Inflammation Leads to Abnormal Embryonic Heart Development.
| العنوان: | Placental Inflammation Leads to Abnormal Embryonic Heart Development. |
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| المؤلفون: | Ward EJ; William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, UK (E.J.W., S.B., S.F., C.G., N.P.D., M.P., F.M.M.-B., S.N.)., Bert S; William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, UK (E.J.W., S.B., S.F., C.G., N.P.D., M.P., F.M.M.-B., S.N.)., Fanti S; William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, UK (E.J.W., S.B., S.F., C.G., N.P.D., M.P., F.M.M.-B., S.N.)., Malone KM; European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK (K.M.M.)., Maughan RT; National Heart and Lung Institute, Imperial College London, UK (R.T.M.)., Gkantsinikoudi C; William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, UK (E.J.W., S.B., S.F., C.G., N.P.D., M.P., F.M.M.-B., S.N.)., Prin F; Crick Advanced Light Microscopy Facility, the Francis Crick Institute, London, UK (F.P.)., Volpato LK; Postgraduate Program in Health Science, University of Southern Catarina, Campus Pedra Branca, Palhoça, SC, Brazil (L.K.V., A.P.P.)., Piovezan AP; Postgraduate Program in Health Science, University of Southern Catarina, Campus Pedra Branca, Palhoça, SC, Brazil (L.K.V., A.P.P.)., Graham GJ; Institute of Infection, Immunity and Inflammation, University of Glasgow, UK (G.J.G.)., Dufton NP; William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, UK (E.J.W., S.B., S.F., C.G., N.P.D., M.P., F.M.M.-B., S.N.)., Perretti M; William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, UK (E.J.W., S.B., S.F., C.G., N.P.D., M.P., F.M.M.-B., S.N.)., Marelli-Berg FM; William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, UK (E.J.W., S.B., S.F., C.G., N.P.D., M.P., F.M.M.-B., S.N.)., Nadkarni S; William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, UK (E.J.W., S.B., S.F., C.G., N.P.D., M.P., F.M.M.-B., S.N.). |
| المصدر: | Circulation [Circulation] 2023 Mar 21; Vol. 147 (12), pp. 956-972. Date of Electronic Publication: 2022 Dec 09. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 0147763 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4539 (Electronic) Linking ISSN: 00097322 NLM ISO Abbreviation: Circulation Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Hagerstown, MD : Lippincott Williams & Wilkins Original Publication: [Dallas, Tex., etc., American Heart Association, etc.] |
| مواضيع طبية MeSH: | Placenta*/pathology , Heart Defects, Congenital*, Pregnancy ; Female ; Mice ; Animals ; Placentation ; Fetus ; Inflammation/pathology |
| مستخلص: | Background: Placental heart development and embryonic heart development occur in parallel, and these organs have been proposed to exert reciprocal regulation during gestation. Poor placentation has been associated with congenital heart disease, an important cause of infant mortality. However, the mechanisms by which altered placental development can lead to congenital heart disease remain unresolved. Methods: In this study, we use an in vivo neutrophil-driven placental inflammation model through antibody depletion of maternal circulating neutrophils at key stages during time-mated murine pregnancy: embryonic days 4.5 and 7.5. Pregnant mice were culled at embryonic day 14.5 to assess placental and embryonic heart development. A combination of flow cytometry, histology, and bulk RNA sequencing was used to assess placental immune cell composition and tissue architecture. We also used flow cytometry and single-cell sequencing to assess embryonic cardiac immune cells at embryonic day 14.5 and histology and gene analyses to investigate embryonic heart structure and development. In some cases, offspring were culled at postnatal days 5 and 28 to assess any postnatal cardiac changes in immune cells, structure, and cardiac function, as measured by echocardiography. Results: In the present study, we show that neutrophil-driven placental inflammation leads to inadequate placental development and loss of barrier function. Consequently, placental inflammatory monocytes of maternal origin become capable of migration to the embryonic heart and alter the normal composition of resident cardiac macrophages and cardiac tissue structure. This cardiac impairment continues into postnatal life, hindering normal tissue architecture and function. Last, we show that tempering placental inflammation can prevent this fetal cardiac defect and is sufficient to promote normal cardiac function in postnatal life. Conclusions: Taken together, these observations provide a mechanistic paradigm whereby neutrophil-driven inflammation in pregnancy can preclude normal embryonic heart development as a direct consequence of poor placental development, which has major implications on cardiac function into adult life. |
| التعليقات: | Comment in: Circulation. 2023 Mar 21;147(12):973-976. (PMID: 36944033) |
| معلومات مُعتمدة: | A18066 United Kingdom CRUK_ Cancer Research UK; FS/17/1/32528 United Kingdom BHF_ British Heart Foundation; 217093 United Kingdom WT_ Wellcome Trust; MR/V010972/1 United Kingdom MRC_ Medical Research Council; CH/15/2/32064 United Kingdom BHF_ British Heart Foundation |
| فهرسة مساهمة: | Keywords: fetus; heart defects, congenital; inflammation; macrophages; mothers; neutrophils; placenta |
| تواريخ الأحداث: | Date Created: 20221209 Date Completed: 20230323 Latest Revision: 20240214 |
| رمز التحديث: | 20240214 |
| مُعرف محوري في PubMed: | PMC10022676 |
| DOI: | 10.1161/CIRCULATIONAHA.122.061934 |
| PMID: | 36484244 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1524-4539 |
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| DOI: | 10.1161/CIRCULATIONAHA.122.061934 |