Changes in gene expression during the early to mid-luteal (receptive phase) transition in human endometrium detected by high-density microarray screening.
High density cDNA microarray screening was used to determine changes in gene expression occurring during the transition between the early luteal (prereceptive) and mid-luteal (receptive) phases in human endometrium. Of approximately 12,000 genes profiled, 693 (5.8%) displayed >2-fold differences in relative levels of expression between these stages. Of these, 370 genes (3.1%) displayed decreases ranging from 2- to >100-fold while 323 genes (2.7%) displayed increases ranging from 2- to >45-fold. Many genes correspond to mRNAs encoding proteins previously shown to change in a similar manner between the proliferative and mid-luteal phases, serving as one validation of the microarray screening results. In addition, novel genes were identified. Genes encoding cell surface receptors, adhesion and extracellular matrix proteins and growth factors accounted for 20% of the changes. Several genes were studied further by Northern blot analyses. These results confirmed that claudin-4/Clostridium perfringens enterotoxin (CPE) receptor and osteopontin (OPN) mRNA increased approximately 4- and 12-fold respectively, while betaig-H3 (BIGH3) decreased >80% during the early to mid-luteal transition. Immunostaining also revealed strong specific staining for claudin-4/CPE, EP(1) and prostaglandin receptor in epithelia, and leukotriene B4 receptor in both epithelia and stroma, at the mid-luteal stage. Collectively, these studies identify multiple new candidate markers that may be used to predict the receptive phase in humans. Some of these gene products, e.g. OPN, may play direct roles in embryo-uterine interactions during the implantation process.
Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA. dcarson@udel.edu
Daniel D
DD
Carson
Errin
E
Lagow
Amantha
A
Thathiah
Rania
R
Al-Shami
Mary C
MC
Farach-Carson
Michael
M
Vernon
Lingwen
L
Yuan
Marc A
MA
Fritz
Bruce
B
Lessey
D015152:Blotting, Northern; D062506:Claudin-4; D010064:Embryo Implantation; D004717:Endometrium / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D006133:Growth Substances / Q000235:genetics; D006801:Humans; D008183:Luteal Phase / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D053495:Osteopontin; D011956:Receptors, Cell Surface / Q000235:genetics; D018102:Receptors, Leukotriene B4 / Q000235:genetics; D011982:Receptors, Prostaglandin / Q000235:genetics; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein
D062506:Claudin-4; D016326:Extracellular Matrix Proteins; D006133:Growth Substances; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D053495:Osteopontin; D011956:Receptors, Cell Surface; D018102:Receptors, Leukotriene B4; D011982:Receptors, Prostaglandin; D012795:Sialoglycoproteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein; C568157:CLDN4 protein, human; C506895:SPP1 protein, human