Role of Foxl2 in uterine maturation and function

Item Type:	Article
Title:	Role of Foxl2 in uterine maturation and function
Creators Name:	Bellessort, B. and Bachelot, A. and Heude, É. and Alfama, G. and Fontaine, A. and Le Cardinal, M. and Treier, M. and Levi, G.
Abstract:	Foxl2 codes for a forkhead/HNF3 transcription factor essential for follicular maturation and maintenance of ovarian identity. FOXL2 mutations are associated with Blepharophimosis, Ptosis, and Epicanthus inversus Syndrome (BPES) characterized by eyelid malformations (type I and II) and premature ovarian insufficiency (type I). We show that Foxl2 is not only expressed by the ovary, but also by other components of the mouse female reproductive tract, including the uterus, the cervix and the oviduct. In the uterus, Foxl2 expression is first observed in the neonatal mesenchyme and, during uterine maturation, persists in the stroma and in the deep inner myometrial layer. In the adult, Foxl2 is expressed in the differentiated stromal layer, but no longer in the myometrium. Conditional deletion of Foxl2 in the postnatal uterus using Progesterone Receptor-cre (Pgr(cre/+)) mice results in infertility. During postnatal uterine maturation Pgr(cre/+); Foxl2(flox/flox) mice present a severely reduced thickness of the stroma layer and an hypertrophic, disorganized inner myometrial layer (IML). In adult Pgr(cre/+); Foxl2(flox/flox) mice a supplementary muscular layer is present at the stroma/myometrium border and vascular smooth muscle cells fail to form a coherent layer around uterine arteries. Wnt signalling pathways play a central role in uterine maturation; in Pgr(cre/+); Foxl2(flox/flox) mice, Wnt genes are deregulated suggesting that Foxl2 acts through these signals. In humans, thickening of the IML (also called "junctional zone") is associated with reduced fertility, endometriosis and adenomyosis. Our data suggest that Foxl2 has a crucial role in postnatal uterine maturation and could help to understand sub-fertility predisposition in women.
Keywords:	Foxl2, Uterus, Myometrium, Post-Natal Maturation, Reproductive Health, Animals, Mice
Source:	Human Molecular Genetics
ISSN:	0964-6906
Publisher:	Oxford University Press
Volume:	24
Number:	11
Page Range:	3092-3103
Date:	1 June 2015
Official Publication:	https://doi.org/10.1093/hmg/ddv061
PubMed:	View item in PubMed

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