Uterine extracellular matrix components are altered during defective decidualization in interleukin-11 receptor alpha deficient mice.
BACKGROUND
Implantation of the embryo and successful pregnancy are dependent on the differentiation of endometrial stromal cells into decidual cells. Female interleukin-11 receptor alpha (IL-11Ralpha) deficient mice are infertile due to disrupted decidualization, suggesting a critical role for IL-11 and its target genes in implantation. The molecular targets of IL-11 in the uterus are unknown, but it is likely that IL-11 signaling modifies the expression of other genes important in decidualization. This study aimed to identify genes regulated by IL-11 during decidualization in mouse uterus, and to examine their expression and localization as an indication of functional significance during early pregnancy.


METHODS
Decidualization was artificially induced in pseudopregnant wild type (IL11Ra+/+) and IL-11Ralpha deficient (IL11Ra-/-) littermates by oil injection into the uterine lumen, and gene expression analyzed by NIA 15K cDNA microarray analysis at subsequent time points. Quantitative real-time RT-PCR was used as an alternative mRNA quantitation method and the expression and cellular localization of the protein products was examined by immunohistochemistry.


RESULTS
Among 15,247 DNA probes, 13 showed increased and 4 decreased expression in IL11Ra-/- uterus at 48 h of decidualization. These included 4 genes encoding extracellular matrix proteins; collagen III alpha1, secreted acidic cysteine-rich glycoprotein (SPARC), biglycan and nidogen-1 (entactin). Immunohistochemistry confirmed increased collagen III and biglycan protein expression in IL11Ra-/- uterus at this time. In both IL11Ra-/- and wild type uterus, collagen III and biglycan were primarily localized to the outer connective tissue and smooth muscle cells of the myometrium, with diffuse staining in the cytoplasm of decidualized stromal cells.


CONCLUSIONS
These data suggest that IL-11 regulates changes in the uterine extracellular matrix that are necessary for decidualization.
White
Christine A
CA
Prince Henry's Institute of Medical Research, Clayton, Victoria 3168, Australia. christine.white@phimr.monash.edu.au
Robb
Lorraine
L
Salamonsen
Lois A
LA
D000818:Animals; D003199:Computer Systems; D003433:Crosses, Genetic; D018076:DNA, Complementary / Q000235:genetics; D003656:Decidua / Q000737:chemistry / Q000378:metabolism / Q000601:surgery; D010064:Embryo Implantation / Q000235:genetics; D005109:Extracellular Matrix / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005796:Genes / Q000235:genetics / Q000276:immunology; D007150:Immunohistochemistry / Q000379:methods; D053703:Interleukin-11 Receptor alpha Subunit; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D046228:Microarray Analysis / Q000379:methods; D009929:Organ Size / Q000235:genetics; D011247:Pregnancy; D011270:Pregnancy, Animal; D018123:Receptors, Interleukin / Q000172:deficiency* / Q000502:physiology; D053702:Receptors, Interleukin-11; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014599:Uterus / Q000166:cytology* / Q000502:physiology
D018076:DNA, Complementary; C508429:Il11ra1 protein, mouse; C508431:Il11ra2 protein, mouse; D053703:Interleukin-11 Receptor alpha Subunit; D018123:Receptors, Interleukin; D053702:Receptors, Interleukin-11