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Uterine defects and estradiol-dependent development of oviductal diverticula in mice lacking the SMAD4 C-terminal Mad homology 2 domain

Authors
  • Petit, Fabrice G.
  • Kervarrec, Christine
  • Allais-Bonnet, Aurélie
  • Evrard, Bertrand
  • Chalmel, Frédéric
  • Deng, Chuxia
  • Jamin, Soazik P
Publication Date
Aug 01, 2023
Identifiers
DOI: 10.1096/fj.202300737R
PMID: 37402125
OAI: oai:HAL:hal-04165713v1
Source
HAL-Descartes
Keywords
Language
English
License
Green
External links

Abstract

In female mammals, the oviduct and uterus are essential sites for female and male gamete transport, fertilization, implantation, and maintenance of a successful pregnancy. To delineate the reproductive function of Mothers against decapentaplegic homolog 4 (Smad4), we specifically inactivated Smad4 in ovarian granulosa cells and, oviduct and uterine mesenchymal cells using the Amhr2-cre mouse line. Deletion of exon 8 of Smad4 results in the production of an MH2-truncated SMAD4 protein. These mutant mice are infertile due to the development of oviductal diverticula and defects during the implantation process. The ovaries are fully functional as demonstrated in an ovary transfer experiment. The development of oviductal diverticula occurs shortly after puberty and is dependent on estradiol. The diverticula interfere with sperm migration and embryo transit to the uterus, reducing the number of implantation sites. Analysis of the uterus shows that, even if implantation occurs, decidualization and vascularization are defective resulting in embryo resorption as early as the seventh day of pregnancy. Thus, Smad4 plays an important function in female reproduction by controlling the structural and functional integrity of the oviduct and uterus.

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