DNA microarray analysis in a mouse model for endometriosis and validation of candidate factors with human adenomyosis.
Gene expression profiling can be of benefit in identifying critical factors in the process of disease initiation and development. However, in endometriosis it has proven difficult to identify common genes between DNA microarray studies, presumably because of tissue homogeneity in lesions and diversity in the patients' conditions. We attempted DNA microarray analysis in a mouse model for endometriosis with stable lesions and a homogeneous genetic background. Data extracted from the mouse model was then evaluated in human tissues. Mice of the ddY strain underwent surgery to remove the left side of the uterine horn, and the uterine tissue was then minced into small segments and auto-transplanted onto the left peritoneum. After 8 weeks, most of the uterine grafts were enlarged and had regenerated lumens. Comparison of the intensity of mRNA expression between grafts and normal uteri showed that genes encoding immune regulators (e.g. CXCL10) and metabolic factors (e.g. calbindin D-28K) were highly up-regulated in the grafts. Strongly inhibited genes in the grafts included prostaglandin-related factors [e.g. prostaglandin E receptor 3 (subtype EP3) and prostaglandin I2 synthase]. Variation in some candidate factors detected in the mouse model was observed by immunohistochemical studies in human adenomyosis tissues. The gene list in the present study is available for re-evaluation of past studies and provides new candidate factors potentially involved in the pathogenesis of endometriosis.
Kusakabe
Ken Takeshi
KT
Department of Laboratory Animal Science, Division of Veterinary Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58 Riku-Ourai kita, Izumisano, Osaka 598-8531, Japan. kkusakabe@vet.osakafu-u.ac.jp
Abe
Hideaki
H
Kondo
Tomohiro
T
Kato
Keiko
K
Okada
Toshiya
T
Otsuki
Yoshinori
Y
D000818:Animals; D064026:Calbindins; D054357:Chemokine CXCL10 / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D015536:Down-Regulation; D004715:Endometriosis / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D056726:Genetic Association Studies; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008815:Mice, Inbred Strains; D020411:Oligonucleotide Array Sequence Analysis; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics; D018078:Receptors, Prostaglandin E / Q000096:biosynthesis / Q000235:genetics; D058308:Receptors, Prostaglandin E, EP3 Subtype; D064030:S100 Calcium Binding Protein G / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation; D014599:Uterus / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000601:surgery
D064026:Calbindins; D054357:Chemokine CXCL10; C545647:PTGER3 protein, human; C545648:Ptger3 protein, mouse; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D064030:S100 Calcium Binding Protein G; D011451:Prostaglandin-Endoperoxide Synthases