BMP7 Induces Uterine Receptivity and Blastocyst Attachment.
In women, the window of implantation is limited to a brief 2- to 3-day period characterized by optimal levels of circulating ovarian hormones and a receptive endometrium. Although the window of implantation is assumed to occur 8 to 10 days after ovulation in women, molecular markers of endometrial receptivity are necessary to determine optimal timing prior to embryo transfer. Previous studies showed that members of the bone morphogenetic protein (BMP) family are expressed in the uterus necessary for female fertility; however, the role of BMP7 during implantation and in late gestation is not known. To determine the contribution of BMP7 to female fertility, we generated Bmp7flox/flox-Pgr-cre+/- [BMP7 conditional knockout (cKO)] mice. We found that absence of BMP7 in the female reproductive tract resulted in subfertility due to uterine defects. At the time of implantation, BMP7 cKO females displayed a nonreceptive endometrium with elevated estrogen-dependent signaling. These implantation-related defects also affected decidualization and resulted in decreased expression of decidual cell markers such as Wnt4, Cox2, Ereg, and Bmp2. We also observed placental abnormalities in pregnant Bmp7 cKO mice, including excessive parietal trophoblast giant cells and absence of a mature placenta at 10.5 days post coitum. To establish possible redundant roles of BMP5 and BMP7 during pregnancy, we generated double BMP5 knockout/BMP7 cKO [BMP5/7 double knockout (DKO)] mice; however, we found that the combined deletion had no additive disruptive effect on fertility. Our studies indicate that BMP7 is an important factor during the process of implantation that contributes to healthy embryonic development.
Departments of Pathology and Immunology, Baylor College of Medicine, Houston, TX.|Center for Reproductive Medicine, Baylor College of Medicine, Houston, TX.
Diana
D
Monsivais
Departments of Pathology and Immunology, Baylor College of Medicine, Houston, TX.|Center for Reproductive Medicine, Baylor College of Medicine, Houston, TX.|Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.|Program in Developmental Biology, Baylor College of Medicine, Houston, Texas.
Caterina
C
Clementi
Departments of Pathology and Immunology, Baylor College of Medicine, Houston, TX.|Center for Reproductive Medicine, Baylor College of Medicine, Houston, TX.|Molecular and Human Genetics,  Baylor College of Medicine, Houston, TX.
Jia
J
Peng
Departments of Pathology and Immunology, Baylor College of Medicine, Houston, TX.|Molecular and Human Genetics,  Baylor College of Medicine, Houston, TX.|Center for Reproductive Medicine, Baylor College of Medicine, Houston, TX.
Paul T
PT
Fullerton
Departments of Pathology and Immunology, Baylor College of Medicine, Houston, TX.|Center for Reproductive Medicine, Baylor College of Medicine, Houston, TX.|Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, Aapistie 5A, Oulu, Finland.
Renata
R
Prunskaite-Hyyryläinen
Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, Aapistie 5A, Oulu, Finland.
Seppo J
SJ
Vainio
Departments of Pathology and Immunology, Baylor College of Medicine, Houston, TX.|Center for Reproductive Medicine, Baylor College of Medicine, Houston, TX.|Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.|Program in Developmental Biology, Baylor College of Medicine, Houston, Texas.|Molecular and Human Genetics,  Baylor College of Medicine, Houston, TX.|Pharmacology, Baylor College of Medicine, Houston, TX.|Center for Drug Discovery, Baylor College of Medicine, Houston, TX .
Martin M
MM
Matzuk
D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism*; D010064:Embryo Implantation / Q000502:physiology*; D005260:Female; D005298:Fertility / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010920:Placenta / Q000378:metabolism*; D010929:Placentation / Q000502:physiology; D011247:Pregnancy; D017154:Stromal Cells / Q000378:metabolism; D014599:Uterus / Q000378:metabolism*
D055419:Bone Morphogenetic Protein 7; C525820:bmp7 protein, mouse