Table 1.
Genes Downregulated in the PR-Null Ovaries and in Response to UPA Treatment at 11 Hours Post-hCG/LH.
| Biological Process | PRKOa | UPAb | Genebank# |
|---|---|---|---|
| Signal transduction | |||
| Cell communication | |||
| ECM protein-mediated signaling | |||
| ADAMTS-1 (a disintegrin and metalloprotease with thrombospondin motif 1) | −4.6 | −6.9 | D67076 |
| Tnfaip6 (tumor necrosis factor alpha induced protein 6) | −2.3 | −4.2 | NM_009398 |
| Ligand-mediated signaling | |||
| ET-2 (endothelin 2: Edn2) | −52.0 | −25.2 | NM_007902 |
| Areg (amphiregulin) | −4.3 | −22.7 | NM_009704 |
| Cell adhesion–mediated signaling | |||
| ADAMTS-4 (a disintegrin and metalloprotease with thrombospondin motif 4) | −3.7 | −3.2 | BB443585 |
| Ptpre (protein tyrosine phosphatase, receptor type, E) | −1.6 | −1.8 | U35368 |
| Cell surface receptor–mediated signaling | |||
| Ereg (epiregulin) | −2.8 | −7.3 | NM_007950 |
| Efnb2 (ephrin B2) | −2.6 | −3.2 | BB453355 |
| EGFR (epidermal growth factor receptor) | −2.6 | −2.5 | U03425 |
| Osmr (oncostatin M receptor) | −3.7 | −2.3 | AB015978 |
| Lepr (leptin receptor) | −1.3 | −2.3 | U42467 |
| Intracellular signaling cascade | |||
| Socs3 (suppressor of cytokine signaling 3) | −5.3 | −4.5 | NM_007707 |
| cGKII (cGMP-dependent protein kinase II; Prkg2) | −5.3 | −5.7 | BB823350 |
| Rras2 (related RAS viral [r-ras] oncogene homolog 2) | −2.5 | −2.8 | BE200500 |
| Sh2b2 (SH2B adaptor protein 2) | −2.6 | −7.5 | NM_018825 |
| Srgap3 (SLIT-ROBO Rho GTPase-activating protein 3) | −1.7 | −1.9 | AF481964 |
| Dusp2 (dual specificity phosphatase 2) | −29.9 | −5.2 | L11330 |
| Developmental process | |||
| Runx1 (Runt-related transcription factor 1) | −4.0 | −1.9 | BI696226 |
| Gas7 (growth arrest specific 7) | −36.8 | −1.6 | NM_008088 |
| Dystrophin | −1.4 | −2.3 | BB085328 |
| Hif1α (hypoxia inducible factor 1α) | −7.5 | −2.1 | BB269715 |
| Hif2α (EPAS1 [endothelial PAS domain protein 1]) | −3.2 | −2.2 | U81983 |
| Hhip (hedgehog-interacting protein) | −1.6 | −7.7 | BB773386 |
| Ifrd1 (interferon-related developmental regulator 1) | −1.3 | −2.0 | NM_013562 |
| Immunity and defense | |||
| Ptgs2 (prostaglandin-endoperoxide synthase 2) | −29.7 | −11.1 | M94967 |
| CXCR4 (C-X-C motif receptor 4) | −4.6 | −1.5 | D87747 |
| IL-6 (interleukin 6) | −13.9 | −21.2 | NM_031168 |
| Clcf1 (cardiotrophin-like cytokine factor 1) | −6.5 | −3.0 | NM_019952 |
| LIF (leukemia inhibitory factor) | −3.3 | −3.0 | BB235045 |
| IL-1r1 (interleukin 1 receptor, type I) | −1.4 | −2.1 | NM_008362 |
| PPARγ (peroxisome proliferator–activated receptor-γ) | −1.3 | −1.5 | NM_011146 |
| Plaur (plasminogen activator, urokinase receptor) | −2.6 | −1.8 | X62701 |
| Prdx2 (peroxiredoxin 2) | −2.3 | −2.0 | AK011963 |
| F3 (coagulation factor III) | −3.5 | −9.5 | BC024886 |
| Ier3 (immediate early response 3) | −2.8 | −3.1 | NM_133662 |
| Xbp1 (X-box binding protein 1) | −2.1 | −1.6 | NM_013842 |
| Klf6 (Kruppel-like factor 6) | −2.1 | −1.8 | BG800611 |
| Nfil3 (nuclear factor, interleukin 3, regulated) | −1.9 | −2.9 | AY061760 |
| Protein modification and metabolism | |||
| Map3k14 (mitogen-activated protein kinase | −2.5 | −1.8 | BG072756 |
| Eif4g1 (eukaryotic translation initiation factor 4, gamma 1) | −4.9 | −1.9 | BB531220 |
| Proteolysis | |||
| MMP19 (matrix metalloproteinase 19) | −7.0 | −2.1 | AV375008 |
| Ctsl (cathepsin L) | −55.7 | −1.5 | AV023994 |
| Usp43 (Ubiquitin specific peptidase 43) | −1.7 | −7.1 | BB831130 |
| Cell structure and motility | |||
| Vinculin | −11.3 | −1.6 | NM_009502 |
| Cldn1 (claudin 1) | −2.5 | −4.0 | AV227581 |
| Versican (Cspg2: chondroitin sulphate proteoglycan 2) | −2.5 | −4.3 | NM_019389 |
| Actn3 (actinin alpha 3) | −4.0 | −2.1 | NM_013456 |
| Pdlim1 (PDZ and LIM domain 1 (elfin)) | −1.5 | −2.1 | NM_016861 |
| Cgn (cingulin) | −2.3 | −1.8 | BI455486 |
| Cell proliferation and differentation | |||
| Sphk1b (sphingosine kinase) | −4.9 | −2.9 | AF068749 |
| Epgn (epithelial mitogen) | −13.0 | −7.0 | NM_053087 |
| C/EBP delta (CCAAT enhancer binding protein, delta) | −3.5 | −3.1 | BB831146 |
| Intracellular protein traffic | |||
| SNAP25 (snaptosomal-associated protein, 25 kD) | −21.1 | −58.6 | BC018249 |
| Vps26a (vacuolar protein sorting 26 homolog A [yeast]) | −1.6 | −1.7 | NM_133672 |
| Arl4a (ADP-ribosylation factor-like 4A) | −1.6 | −1.5 | AK006286 |
| Transport | |||
| Slc2a1 (solute carrier family 2 [facilitated glucose transporter], member 1; GLUT1) | −1.5 | −2.0 | M23384 |
| Slc7a8 (solute carrier family 7 [cationic amino acid transporter, y+ system], member 8) | −2.0 | −1.7 | NM_016972 |
| Slc7a11 (solute carrier family 7 [cationic amino acid transporter, y+ system], member 11) | −3.7 | −3.9 | NM_011990 |
| Apoa1 (apolipoprotein A-I) | −4.3 | −3.4 | NM_009692 |
| Clcn6 (chloride channel 6) | −6.1 | −2.1 | NM_011929 |
| Cacna2d1 (calcium channel, voltage-dependent, alpha2/delta subunit 1) | −3.2 | −2.7 | BB629558 |
| Apoptosis | |||
| Sphk1 (sphingosine kinase 1) | −4.9 | −2.9 | AF068749 |
| Axud1 (AXIN1 upregulated 1) | −2.8 | −4.3 | BG070296 |
| Cell adhesion | |||
| Loxl2 (lysyl oxidase-like protein 2) | −2.3 | −2.1 | AF117951 |
| Jam3 (junction adhesion molecule 3) | −1.7 | −2.7 | AK013156 |
| Pkp2 (plakophilin 2) | −1.5 | −2.0 | AK005020 |
| Porcn (porcupine homolog [Drosophila]) | −4.0 | −2.3 | AB036749 |
| Cell cycle | |||
| Cyr61 (cysteine rich protein 61) | −4.3 | −4.5 | BM202770 |
| Hira (histone cell cycle regulation defective homolog A) | −2.5 | −1.6 | NM_010435 |
| Junb (Jun-B oncogene) | −17.2 | −1.9 | NM_008416 |
| Dusp4 (Dual specificity phosphatase 4) | −1.6 | −3.2 | AK012530 |
| Top1 (topoisomerase [DNA] I) | −1.4 | −1.6 | BB127876 |
| Hmga1 (high mobility group AT-hook 1) | −3.0 | −2.3 | NM_016660 |
| Fos (FBJ osteosarcoma oncogene) | −2.6 | −3.1 | AV026617 |
| Unclassified | |||
| IL-11 (interleukin 11) | −8.6 | −7.5 | NM_008350 |
| Mt2 (metallothionein 2) | −5.3 | −3.5 | AA796766 |
| Scara5 (scavenger receptor class A, member 5 [putative]) | −3.5 | −2.4 | BC016096 |
| Tnfrsf12a (tumor necrosis factor receptor superfamily, member 12a) | −3.5 | −2.1 | NM_013749 |
a Wild-type and PR-null mice (PRKO) were superovulated and ovaries were collected at 11 hours post-hCG. Ovarian RNAs were analyzed by microarrays (GeneChip Mouse Genome 430 2.0 array, Affymetrix, Santa Clara, California).27 The GEO accession number for the microarray data is GSE37383. The values are individual fold changes with “–” sign, representing a decrease in gene expression in PR-null ovaries compared to that of wild type. The genes were classified according to known biological functions (Panther: http://www.pantherdb.org/).
b Mice were superovulated as described in Materials and Methods section. They were treated with vehicle or ulipristal acetate (UPA) at 2 hours post-hCG and ovaries were collected at 11 hours post-hCG. Ovarian RNAs were analyzed by microarrays (GeneChip). The GEO accession number for the microarray data is GSE37383. The values are individual fold changes with “–” sign representing a decrease in gene expression in response to UPA treatment compared to that of vehicle. The genes were classified according to known biological functions (Panther: http://www.pantherdb.org/).