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OSR1 disruption contributes to uterine factor infertility via impaired Müllerian duct development and endometrial receptivity.
Lofrano-Porto, Adriana; Pereira, Sidney Alcântara; Dauber, Andrew; Bloom, Jordana Cb; Fontes, Audrey N; Asimow, Naomi; de Moraes, Olívia Laquis; Araujo, Petra Ariadne T; Abreu, Ana Paula; Guo, Michael H; De Oliveira, Silviene F; Liu, Han; Lee, Charles; Kuohung, Wendy; Coelho, Michella S; Carroll, Rona S; Jiang, Rulang; Kaiser, Ursula B.
Afiliação
  • Lofrano-Porto A; Molecular Pharmacology Laboratory (FARMOL), Faculty of Health Sciences, University of Brasilia, Brasilia-DF, Brazil.
  • Pereira SA; Section of Endocrinology, Gonadal and Adrenal Diseases Clinics, University Hospital of Brasilia, Brasilia-DF, Brazil.
  • Dauber A; Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  • Bloom JC; Molecular Pharmacology Laboratory (FARMOL), Faculty of Health Sciences, University of Brasilia, Brasilia-DF, Brazil.
  • Fontes AN; Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  • Asimow N; Division of Endocrinology, Children's National Hospital, Washington, DC, USA.
  • de Moraes OL; Department of Pediatrics, George Washington School of Medicine and Health Sciences, Washington, DC, USA.
  • Araujo PAT; Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA.
  • Abreu AP; Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  • Guo MH; Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  • De Oliveira SF; Molecular Pharmacology Laboratory (FARMOL), Faculty of Health Sciences, University of Brasilia, Brasilia-DF, Brazil.
  • Liu H; Molecular Pharmacology Laboratory (FARMOL), Faculty of Health Sciences, University of Brasilia, Brasilia-DF, Brazil.
  • Lee C; Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  • Kuohung W; Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts, USA.
  • Coelho MS; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
  • Carroll RS; Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
  • Jiang R; Department of Genetics and Morphology, Institute of Biology, University of Brasilia, Brasilia-DF, Brazil.
  • Kaiser UB; Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA.
J Clin Invest ; 133(23)2023 Dec 01.
Article em En | MEDLINE | ID: mdl-37847567
Three sisters, born from consanguineous parents, manifested a unique Müllerian anomaly characterized by uterine hypoplasia with thin estrogen-unresponsive endometrium and primary amenorrhea, but with spontaneous tubal pregnancies. Through whole-exome sequencing followed by comprehensive genetic analysis, a missense variant was identified in the OSR1 gene. We therefore investigated OSR1/OSR1 expression in postpubertal human uteri, and the prenatal and postnatal expression pattern of Osr1/Osr1 in murine developing Müllerian ducts (MDs) and endometrium, respectively. We then investigated whether Osr1 deletion would affect MD development, using WT and genetically engineered mice. Human uterine OSR1/OSR1 expression was found primarily in the endometrium. Mouse Osr1 was expressed prenatally in MDs and Wolffian ducts (WDs), from rostral to caudal segments, in E13.5 embryos. MDs and WDs were absent on the left side and MDs were rostrally truncated on the right side of E13.5 Osr1-/- embryos. Postnatally, Osr1 was expressed in mouse uteri throughout their lifespan, peaking at postnatal days 14 and 28. Osr1 protein was present primarily in uterine luminal and glandular epithelial cells and in the epithelial cells of mouse oviducts. Through this translational approach, we demonstrated that OSR1 in humans and mice is important for MD development and endometrial receptivity and may be implicated in uterine factor infertility.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Infertilidade / Ductos Paramesonéfricos Limite: Animals / Female / Humans / Pregnancy Idioma: En Revista: J Clin Invest Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos
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: Infertilidade / Ductos Paramesonéfricos Limite: Animals / Female / Humans / Pregnancy Idioma: En Revista: J Clin Invest Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos