The Endometrial Response to Chorionic Gonadotropin Is Blunted in a Baboon Model of Endometriosis
| Autor: | Andrew M. Sharkey, Julie Hastings, Asgerally T. Fazleabas, Patricia A. Mavrogianis, J. R A Sherwin, Kevin S. Jackson |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Infertility
Male medicine.medical_specialty endocrine system medicine.drug_class media_common.quotation_subject Uterus Endometriosis Down-Regulation Biology Endometrium Chorionic Gonadotropin Article Biomarkers Pharmacological Human chorionic gonadotropin Endocrinology Internal medicine medicine Animals Cluster Analysis Humans Ovulation reproductive and urinary physiology media_common Oligonucleotide Array Sequence Analysis Uterine Diseases Genome urogenital system Gene Expression Profiling Decidualization medicine.disease Disease Models Animal medicine.anatomical_structure Female Rabbits Gonadotropin hormones hormone substitutes and hormone antagonists Papio |
| Popis: | Endometriosis-associated infertility has a multifactorial etiology. We tested the hypothesis that the endometrial response to the early embryonic signal, human chorionic gonadotropin (hCG), alters over time in a nonhuman primate model of endometriosis. Animals with experimental or spontaneous endometriosis were treated with hCG (30 IU/d), from d 6 after ovulation for 5 d, via an oviductal cannula. Microarray analysis of endometrial transcripts from baboons treated with hCG at 3 and 6 months of disease (n = 6) identified 22 and 165 genes, respectively, whose levels differed more than 2-fold compared with disease-free (DF) animals treated with hCG (P < 0.01). Quantitative RT-PCR confirmed abnormal responses of known hCG-regulated genes. APOA1, SFRP4, and PAPPA, which are normally down-regulated by hCG were up-regulated by hCG in animals with endometriosis. In contrast, the ability of hCG to induce SERPINA3 was lost. Immunohistochemistry demonstrated dysregulation of C3 and superoxide dismutase 2 proteins. We demonstrate that this abnormal response to hCG persists for up to 15 months after disease induction and that the nature of the abnormal response changes as the disease progresses. Immunohistochemistry showed that this aberrant gene expression was not a consequence of altered LH/choriogonadotropin receptor distribution in the endometrium of animals with endometriosis. We have shown that endometriosis induces complex changes in the response of eutopic endometrium to hCG, which may prevent the acquisition of the full endometrial molecular repertoire necessary for decidualization and tolerance of the fetal allograft. This may in part explain endometriosis-associated implantation failure. |
| Databáze: | OpenAIRE |
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