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Highlight Article: Different morphological and gene expression profile in placentas of the same sickle cell anemia patient in pregnancies of opposite outcomes

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Autor(es):
Baptista, Leticia C. [1] ; Figueira, Camilla O. [2] ; Souza, Bruno B. [1] ; Fertrin, Kleber Y. [3] ; Antolini, Arthur [4] ; Costa, Fernando F. [5] ; de Melo, Monica B. [1] ; Costa, Maria Laura [2]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Univ Estadual Campinas, UNICAMP, Ctr Mol Biol & Genet Engn CBMEG, BR-13083875 Campinas, SP - Brazil
[2] Univ Estadual Campinas, UNICAMP, Dept Obstet & Gynecol, BR-13083880 Campinas, SP - Brazil
[3] Univ Washington, Div Hematol, Seattle, WA 98195 - USA
[4] Univ Estadual Campinas, UNICAMP, Dept Pathol, BR-13083887 Campinas, SP - Brazil
[5] Univ Estadual Campinas, UNICAMP, Hematol & Hemotherapy Ctr, BR-13083878 Campinas, SP - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: Experimental Biology and Medicine; v. 244, n. 5, p. 395-403, APR 2019.
Citações Web of Science: 0
Resumo

Environmentally induced changes in placental morphological and molecular phenotypes may provide relevant insight towards pathophysiology of diseases. Sickle cell disease (SCD) is a common inherited hemoglobin disorder characterized by chronic hemolytic anemia and vaso-occlusive crisis. SCD leads to higher morbidity and mortality, especially during pregnancy, with increased risk of preeclampsia (PE). To compare clinical findings, placental morphology, and gene expression in villous placental tissue using next generation sequencing. We included five cases. Two placentas from the same woman with homozygous SCD that had been pregnant twice and had different maternal and fetal outcomes (one early onset PE/eclampsia and a mostly non-complicated pregnancy); an early onset PE, a fetal growth restriction and a term, non-complicated pregnancy. Sixty-four differentially expressed genes were observed in the SCD+PE case, in comparison with the placenta from the SCD without PE, based on fold change. Among these genes, 59 were upregulated and 5 were downregulated. Enrichment analysis indicated two significant biological processes: response to copper ion (CYP1A1, AOC1, AQP1, and ATP5D) and triglyceride-rich lipoprotein particle clearance (GPIHBP1, APOC1, and APOE). The rare opportunity to evaluate the same patient in two different pregnancies, of opposing outcomes, and compare to other conditions of known placental and vascular/inflammatory involvement, may further the understanding of the pathophysiology of PE in SCD. Our results suggest that the clinical association between SCD and PE may be supported by common pathophysiological mechanisms, but that pathways involving response to copper and triglyceride metabolism could be important drivers of PE pathophysiology. Impact statement Environmentally induced changes in placental morphological and molecular phenotypes may provide relevant insight towards pathophysiology of diseases. The rare opportunity to evaluate the same patient, with sickle cell anemia (SCA), in two different pregnancies, of opposite outcomes (one early onset severe preeclampsia (PE) and the other mostly non-complicated) can prove such concept. In addition, the comparison to other conditions of known placental and vascular/inflammatory involvement strengthens such findings. Our results suggest that the clinical association between SCA and PE can be supported by common pathophysiological mechanisms, but that pathways involving response to copper and triglyceride metabolism may be important drivers of the pathophysiology of PE. Future studies using in a larger number of samples should confirm these findings and explore pathways involved in the pathophysiology of PE and its relationship with SCA. (AU)

Processo FAPESP: 15/08330-5 - Transcriptômica em placentas de pacientes portadoras de doença falciforme
Beneficiário:Letícia de Carvalho Baptista
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 14/00984-3 - Doenças dos glóbulos vermelhos: fisiopatologia e novas abordagens terapêuticas
Beneficiário:Fernando Ferreira Costa
Linha de fomento: Auxílio à Pesquisa - Temático