FOXD1 mutations are related to repeated implantation failure, intra-uterine growth restriction and preeclampsia

Título traducido de la contribución: Mutaciones en FOXD1 estan relacionados con falla de implantacion, restriccion del crecimiento intra-uterino y preeclampsia

Paula Quintero-Ronderos, Karen Marcela Jiménez, Clara Esteban-Perez, Diego Ojeda, Sandra Bello, Dora Janeth Fonseca Mendoza, María Alejandra Coronel, Harold Moreno-Ortiz, Diana Carolina Sierra Díaz, Elkin Lucena, Sandrine Barbaux, Daniel Vaiman, Paul Laissue Hormaza

Producción científica: Contribución a una revistaArtículo de Investigaciónrevisión exhaustiva

13 Citas (Scopus)


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. Keywords: Recurrent pregnancy loss, Preeclampsia, Intra-uterine growth restriction, FOXD1
Título traducido de la contribuciónMutaciones en FOXD1 estan relacionados con falla de implantacion, restriccion del crecimiento intra-uterino y preeclampsia
Idioma originalInglés
Número de artículo37
Páginas (desde-hasta)37-45
Número de páginas8
PublicaciónMolecular Medicine
EstadoPublicada - ago. 8 2019

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