Differential Wnt signaling activity limits epithelial gland development to the anti-mesometrial side of the mouse uterus.
In mice, implantation always occurs towards the antimesometrial side of the uterus, while the placenta develops at the mesometrial side. What determines this particular orientation of the implanting blastocyst remains unclear. Uterine glands are critical for implantation and pregnancy. In this study, we showed that uterine gland development and active Wnt signaling activity is limited to the antimesometrial side of the uterus. Dkk2, a known antagonist of Wnt signaling, is only present at the mesometrial side of the uterus. Imaging of whole uterus, thick uterine sections (100-1000µm), and individual glands revealed that uterine glands are simple tubes with branches that are directly connected to the luminal epithelium and are only present towards the antimesometrial side of the uterus. By developing a unique mouse model targeting the uterine epithelium, we demonstrated that Wnt/β-catenin signaling is essential for prepubertal gland formation and normal implantation, but dispensable for postpartum gland development and regeneration. Our results for the first time have provided a probable explanation for the antimesometrial bias for implantation.
School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales 2308, Australia.
Jyoti
J
Goad
School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales 2308, Australia.
Yi-An
YA
Ko
School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales 2308, Australia.
Manish
M
Kumar
School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales 2308, Australia.
Shafiq M
SM
Syed
School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales 2308, Australia. Electronic address: pradeep.tanwar@newcastle.edu.au.
Pradeep S
PS
Tanwar
D000818:Animals; D010064:Embryo Implantation / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D005260:Female; D005298:Fertility / Q000187:drug effects; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D049590:Postpartum Period / Q000187:drug effects; D011374:Progesterone / Q000494:pharmacology; D012741:Sexual Maturation / Q000187:drug effects; D014599:Uterus / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism
C405060:Dkk2 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D051176:beta Catenin; D011374:Progesterone
Endometrial glands; Implantation; Mouse uterus; Pregnancy; Wnt