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FOXD1 mutations are related to repeated implantation failure, intra-uterine growth restriction and preeclampsia.
Quintero-Ronderos, Paula; Jiménez, Karen Marcela; Esteban-Pérez, Clara; Ojeda, Diego A; Bello, Sandra; Fonseca, Dora Janeth; Coronel, María Alejandra; Moreno-Ortiz, Harold; Sierra-Díaz, Diana Carolina; Lucena, Elkin; Barbaux, Sandrine; Vaiman, Daniel; Laissue, Paul.
Afiliação
  • Quintero-Ronderos P; Center For Research in Genetics and Genomics-CIGGUR. GENIUROS Research Group. School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia.
  • Jiménez KM; Center For Research in Genetics and Genomics-CIGGUR. GENIUROS Research Group. School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia.
  • Esteban-Pérez C; Fertility and Sterility Colombian Center, Department of Reproductive Genetics, Bogotá, Colombia.
  • Ojeda DA; Center For Research in Genetics and Genomics-CIGGUR. GENIUROS Research Group. School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia.
  • Bello S; Clinical Neurosciences and Psychiatry, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK., Southampton, United Kingdom.
  • Fonseca DJ; Center For Research in Genetics and Genomics-CIGGUR. GENIUROS Research Group. School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia.
  • Coronel MA; Center For Research in Genetics and Genomics-CIGGUR. GENIUROS Research Group. School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia.
  • Moreno-Ortiz H; Center For Research in Genetics and Genomics-CIGGUR. GENIUROS Research Group. School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia.
  • Sierra-Díaz DC; Fertility and Sterility Colombian Center, Department of Reproductive Genetics, Bogotá, Colombia.
  • Lucena E; Center For Research in Genetics and Genomics-CIGGUR. GENIUROS Research Group. School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia.
  • Barbaux S; Fertility and Sterility Colombian Center, Department of Reproductive Genetics, Bogotá, Colombia.
  • Vaiman D; Inserm U1016, CNRS UMR8104, Institut Cochin, équipe FGTB, 24, rue du faubourg Saint-Jacques, 75014, Paris, France.
  • Laissue P; Inserm U1016, CNRS UMR8104, Institut Cochin, équipe FGTB, 24, rue du faubourg Saint-Jacques, 75014, Paris, France.
Mol Med ; 25(1): 37, 2019 08 08.
Article em En | MEDLINE | ID: mdl-31395028
BACKGROUND: Human reproductive disorders consist of frequently occurring dysfunctions including a broad range of phenotypes affecting fertility and women's health during pregnancy. Several female-related diseases have been associated with hypofertility/infertility phenotypes, such as recurrent pregnancy loss (RPL). Other occurring diseases may be life-threatening for the mother and foetus, such as preeclampsia (PE) and intra-uterine growth restriction (IUGR). FOXD1 was defined as a major molecule involved in embryo implantation in mice and humans by regulating endometrial/placental genes. FOXD1 mutations in human species have been functionally linked to RPL's origin. METHODS: FOXD1 gene mutation screening, in 158 patients affected by PE, IUGR, RPL and repeated implantation failure (RIF), by direct sequencing and bioinformatics analysis. Plasmid constructs including FOXD1 mutations were used to perform in vitro gene reporter assays. RESULTS: Nine non-synonymous sequence variants were identified. Functional experiments revealed that p.His267Tyr and p.Arg57del led to disturbances of promoter transcriptional activity (C3 and PlGF genes). The FOXD1 p.Ala356Gly and p.Ile364Met deleterious mutations (previously found in RPL patients) have been identified in the present work in women suffering PE and IUGR. CONCLUSIONS: Our results argue in favour of FOXD1 mutations' central role in RPL, RIF, IUGR and PE pathogenesis via C3 and PlGF regulation and they describe, for the first time, a functional link between FOXD1 and implantation/placental diseases. FOXD1 could therefore be used in clinical environments as a molecular biomarker for these diseases in the near future.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pré-Eclâmpsia / Aborto Habitual / Predisposição Genética para Doença / Fatores de Transcrição Forkhead / Retardo do Crescimento Fetal Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Pregnancy Idioma: En Revista: Mol Med Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Colômbia País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pré-Eclâmpsia / Aborto Habitual / Predisposição Genética para Doença / Fatores de Transcrição Forkhead / Retardo do Crescimento Fetal Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Pregnancy Idioma: En Revista: Mol Med Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Colômbia País de publicação: Reino Unido