Association of FOXD1 variants with adverse pregnancy outcomes in mice and humans
Recurrent spontaneous abortion (RSA) is a common cause of infertility, but previous attempts at identifying RSA causative genes have been relatively unsuccessful. Such failure to describe RSA aetiological genes might be explained by the fact that reproductive phenotypes should be considered as quant...
- Autores:
- Tipo de recurso:
- Fecha de publicación:
- 2016
- Institución:
- Universidad del Rosario
- Repositorio:
- Repositorio EdocUR - U. Rosario
- Idioma:
- eng
- OAI Identifier:
- oai:repository.urosario.edu.co:10336/21963
- Acceso en línea:
- https://doi.org/10.1098/rsob.160109
https://repository.urosario.edu.co/handle/10336/21963
- Palabra clave:
- Evolución & genética
Ginecología & otras especialidades médicas
Developmental biology
Genetics
Genomics
FOXD1 protein
Embryo death
Recurrent spontaneous abortion
Interspecific recombinant congenic mice
DNA microarray
Forkhead transcription factor
Chlorocebus aethiops
C57BL mouse
CV-1 cell line
- Rights
- License
- Abierto (Texto Completo)
| Summary: | Recurrent spontaneous abortion (RSA) is a common cause of infertility, but previous attempts at identifying RSA causative genes have been relatively unsuccessful. Such failure to describe RSA aetiological genes might be explained by the fact that reproductive phenotypes should be considered as quantitative traits resulting from the intricate interaction of numerous genetic, epigenetic and environmental factors. Here, we studied an interspecific recombinant congenic strain (IRCS) of Mus musculus from the C57BL6/J strain of mice harbouring an approximate 5 Mb DNA fragment from chromosome 13 from Mus spretus mice (66H-MMU13 strain), with a high rate of embryonic resorption (ER). Transcriptome analyses of endometrial and placental tissues from these mice showed a deregulation of many genes associated with the coagulation and inflammatory response pathways. Bioinformatics approaches led us to select Foxd1 as a candidate gene potentially related to ER and RSA. Sequencing analysis of Foxd1 in the 66H-MMU13 strain, and in 556 women affected by RSA and 271 controls revealed non-synonymous sequence variants. In vitro assays revealed that some led to perturbations in FOXD1 transactivation properties on promoters of genes having key roles during implantation/placentation, suggesting a role of this gene in mammalian implantation processes. © 2016 The Authors. |
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