title: Cochaperone immunophilin FKBP52 is critical to uterine receptivity for embryo implantation.
abstract: Embryo implantation in the uterus is a critical step in mammalian reproduction, requiring preparation of the uterus receptive to blastocyst implantation. Uterine receptivity, also known as the window of implantation, lasts for a limited period, and it is during this period blastocysts normally implant. Ovarian steroid hormones estrogen and progesterone (P(4)) are the primary regulators of this process. The immunophilin FKBP52 serves as a cochaperone for steroid hormone nuclear receptors to govern appropriate hormone action in target tissues. Here we show a critical role for FKBP52 in mouse implantation. This immunophilin has unique spatiotemporal expression in the uterus during implantation, and females missing the Fkbp52 gene have complete implantation failure due to lack of attainment of uterine receptivity. The overlapping uterine expression of FKBP52 with nuclear progesterone receptor (PR) in wild-type mice together with reduced P(4) binding to PR, attenuated PR transcriptional activity and down-regulation of several P(4)-regulated genes in uteri of Fkbp52(-/-) mice, establishes this cochaperone as a critical regulator of uterine P(4) function. Interestingly, ovulation, another P(4)-mediated event, remains normal. Collectively, the present investigation provides evidence for an in vivo role for this cochaperone in regulating tissue-specific hormone action and its critical role in uterine receptivity for implantation.
authors.affiliation: Departments of Pediatrics, Cell and Developmental Biology, Cancer Biology, and Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Susanne
authors.initials: S
authors.lastname: Tranguch
authors.forename: Joyce
authors.initials: J
authors.lastname: Cheung-Flynn
authors.forename: Takiko
authors.initials: T
authors.lastname: Daikoku
authors.forename: Viravan
authors.initials: V
authors.lastname: Prapapanich
authors.forename: Marc B
authors.initials: MB
authors.lastname: Cox
authors.forename: Huirong
authors.initials: H
authors.lastname: Xie
authors.forename: Haibin
authors.initials: H
authors.lastname: Wang
authors.forename: Sanjoy K
authors.initials: SK
authors.lastname: Das
authors.forename: David F
authors.initials: DF
authors.lastname: Smith
authors.forename: Sudhansu K
authors.initials: SK
authors.lastname: Dey
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D015536:Down-Regulation; D010064:Embryo Implantation / Q000502:physiology*; D005260:Female; D006652:Histological Techniques; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018832:Molecular Chaperones / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D022021:Tacrolimus Binding Proteins / Q000378:metabolism*; D014599:Uterus / Q000378:metabolism* / Q000502:physiology
chemical_list: D018832:Molecular Chaperones; D011980:Receptors, Progesterone; D011374:Progesterone; D022021:Tacrolimus Binding Proteins; C403485:tacrolimus binding protein 4