Germ cell specific overactivation of WNT/βcatenin signalling has no effect on folliculogenesis but causes fertility defects due to abnormal foetal development.
All the major components of the WNT signalling pathway are expressed in female germ cells and embryos. However, their functional relevance in oocyte biology is currently unclear. We examined ovaries collected from TCFGFP mice, a well-known Wnt reporter mouse model, and found dynamic changes in the Wnt/βcatenin signalling activity during different stages of oocyte development and maturation. To understand the functional importance of Wnt signalling in oocytes, we developed a mouse model with the germ cell-specific constitutive activation of βcatenin using cre recombinase driven by the DEAD (Asp-Glu-Ala-Asp) box protein 4 (Ddx4) gene promoter. Histopathological and functional analysis of ovaries from these mutant mice (Ctnnb1(ex3)cko) showed no defects in ovarian functions, oocytes, ovulation and early embryonic development. However, breeding of the Ctnnb1(ex3)cko female mice with males of known fertility never resulted in birth of mutant pups. Examination of uteri from time pregnant mutant females revealed defects in ectoderm differentiation leading to abnormal foetal development and premature death. Collectively, our work has established the role of active WNT/βcatenin signalling in oocyte biology and foetal development, and provides novel insights into the possible mechanisms of complications in human pregnancy such as repeated spontaneous abortion, sudden intrauterine unexpected foetal death syndrome and stillbirth.
Gynaecology Oncology Group, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia.
Manish
M
Kumar
Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales, Australia.
Nicole J
NJ
Camlin
Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales, Australia.
Janet E
JE
Holt
Department of Obstetrics, Gynaecology and Reproductive Biology, College of Human Medicine, Michigan State University, 333 Bostwick Ave NE, 4018A, Grand Rapids, MI, USA.|Department of Women's Health, Spectrum Health Systems, Grand Rapids, MI, USA.
Jose M
JM
Teixeira
Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales, Australia.
Eileen A
EA
McLaughlin
Gynaecology Oncology Group, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia.
Pradeep S
PS
Tanwar
D000818:Animals; D001947:Breeding; D005260:Female; D047109:Fetal Development; D007246:Infertility / Q000209:etiology*; D051379:Mice; D009154:Mutation; D009865:Oocytes / Q000254:growth & development* / Q000378:metabolism*; D009866:Oogenesis; D011247:Pregnancy; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics
C495267:CTNNB1 protein, mouse; D051176:beta Catenin