PMID- 28203817
OWN - NLM
STAT- MEDLINE
DCOM- 20180627
LR  - 20190508
IS  - 1529-7268 (Electronic)
IS  - 0006-3363 (Print)
IS  - 0006-3363 (Linking)
VI  - 96
IP  - 2
DP  - 2017 Feb 1
TI  - Decreased epithelial progesterone receptor A at the window of receptivity is 
      required for preparation of the endometrium for embryo attachment.
PG  - 313-326
LID - 10.1095/biolreprod.116.144410 [doi]
AB  - The precise timing of progesterone signaling through its cognate receptor, the 
      progesterone receptor (PGR), is critical for the establishment and maintenance of 
      pregnancy. Loss of PGR expression in the murine uterine epithelium during the 
      preimplantation period is a marker for uterine receptivity and embryo attachment. 
      We hypothesized that the decrease in progesterone receptor A (PGRA) expression is 
      necessary for successful embryo implantation. To test this hypothesis, a mouse 
      model constitutively expressing PGRA (mPgrALsL/+) was generated. Expression of 
      PGRA in all uterine compartments (Pgrcre) or uterine epithelium (Wnt7acre) 
      resulted in infertility with defects in embryo attachment and stromal 
      decidualization. Expression of critical PGRA target genes, indian hedgehog, and 
      amphiregulin (Areg), was maintained through the window of receptivity while the 
      estrogen receptor target gene, the leukemia inhibitory factor (Lif), a key 
      regulator of embryo receptivity, was decreased. Transcriptomic and cistromic 
      analyses of the mouse uterus at day 4.5 of pregnancy identified an altered group 
      of genes regulating molecular transport in the control of fluid and ion levels 
      within the uterine interstitial space. Additionally, LIF and its cognate 
      receptor, the leukemia inhibitory factor receptor (LIFR), exhibited PGR-binding 
      events in regions upstream of the transcriptional start sites, suggesting PGRA is 
      inhibiting transcription at these loci. Therefore, downregulation of the PGRA 
      isoform at the window of receptivity is necessary for the attenuation of hedgehog 
      signaling, transcriptional activation of LIF signaling, and modulation of solutes 
      and fluid, producing a receptive environment for the attaching embryo.
FAU - Wetendorf, Margeaux
AU  - Wetendorf M
AD  - Reproductive and Developmental Biology Laboratory, National Institute of 
      Environmental Health Sciences, Research Triangle Park, Durham, North Carolina, 
      USA.
AD  - Department of Molecular and Cellular Biology, Baylor College of Medicine, 
      Houston, Texas, USA.
AD  - Integrative Molecular and Biomedical Sciences Graduate Program, Baylor College of 
      Medicine, Houston, Texas, USA.
FAU - Wu, San-Pin
AU  - Wu SP
AD  - Reproductive and Developmental Biology Laboratory, National Institute of 
      Environmental Health Sciences, Research Triangle Park, Durham, North Carolina, 
      USA.
FAU - Wang, Xiaoqiu
AU  - Wang X
AD  - Reproductive and Developmental Biology Laboratory, National Institute of 
      Environmental Health Sciences, Research Triangle Park, Durham, North Carolina, 
      USA.
FAU - Creighton, Chad J
AU  - Creighton CJ
AD  - Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, 
      Texas, USA.
FAU - Wang, Tianyuan
AU  - Wang T
AD  - Integrative Bioinformatics, National Institute of Environmental Health Sciences, 
      Research Triangle Park, Durham, North Carolina, USA.
FAU - Lanz, Rainer B
AU  - Lanz RB
AD  - Department of Molecular and Cellular Biology, Baylor College of Medicine, 
      Houston, Texas, USA.
FAU - Blok, Leen
AU  - Blok L
AD  - Department of Obstetrics and Gynaecology, Erasmus MC Cancer Institute, University 
      Medical Center Rotterdam, Rotterdam, The Netherlands.
FAU - Tsai, Sophia Y
AU  - Tsai SY
AD  - Department of Molecular and Cellular Biology, Baylor College of Medicine, 
      Houston, Texas, USA.
FAU - Tsai, Ming-Jer
AU  - Tsai MJ
AD  - Department of Molecular and Cellular Biology, Baylor College of Medicine, 
      Houston, Texas, USA.
FAU - Lydon, John P
AU  - Lydon JP
AD  - Department of Molecular and Cellular Biology, Baylor College of Medicine, 
      Houston, Texas, USA.
FAU - DeMayo, Francesco J
AU  - DeMayo FJ
AD  - Reproductive and Developmental Biology Laboratory, National Institute of 
      Environmental Health Sciences, Research Triangle Park, Durham, North Carolina, 
      USA.
LA  - eng
GR  - R01 DK045641/DK/NIDDK NIH HHS/United States
GR  - R01 HD042311/HD/NICHD NIH HHS/United States
GR  - R01 HL114539/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Biol Reprod
JT  - Biology of reproduction
JID - 0207224
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Receptors, OSM-LIF)
RN  - 0 (Receptors, Progesterone)
RN  - 0 (Wnt Proteins)
RN  - 0 (Wnt7a protein, mouse)
RN  - 0 (progesterone receptor A)
RN  - 4G7DS2Q64Y (Progesterone)
SB  - IM
MH  - Alleles
MH  - Animals
MH  - Cloning, Molecular
MH  - Down-Regulation
MH  - *Embryo Implantation
MH  - *Endometrium
MH  - Female
MH  - Gene Expression Regulation/physiology
MH  - Hedgehog Proteins/genetics/metabolism
MH  - Male
MH  - Mice, Transgenic
MH  - Progesterone/*metabolism
MH  - Receptors, OSM-LIF/genetics/metabolism
MH  - Receptors, Progesterone/genetics/*metabolism
MH  - Wnt Proteins/genetics/metabolism
PMC - PMC6225975
OTO - NOTNLM
OT  - progesterone receptor
OT  - implantation
OT  - uterine receptivity
OT  - progesterone signaling
OT  - mouse models
EDAT- 2017/02/17 06:00
MHDA- 2018/06/28 06:00
PMCR- 2017/01/24
CRDT- 2017/02/17 06:00
PHST- 2017/01/03 00:00 [accepted]
PHST- 2016/08/22 00:00 [received]
PHST- 2016/12/23 00:00 [revised]
PHST- 2017/02/17 06:00 [entrez]
PHST- 2017/02/17 06:00 [pubmed]
PHST- 2018/06/28 06:00 [medline]
PHST- 2017/01/24 00:00 [pmc-release]
AID - 2948761 [pii]
AID - bio144410 [pii]
AID - 10.1095/biolreprod.116.144410 [doi]
PST - ppublish
SO  - Biol Reprod. 2017 Feb 1;96(2):313-326. doi: 10.1095/biolreprod.116.144410.