Tissue inhibitor of metalloproteinase-1 contributes to reduced fecundity in a rat model of endometriosis
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[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Endometriosis affects millions of women worldwide; its symptoms are pain and reduced fecundity. An established rat model was used which endometriosis is surgically induced (Endo) was compared to surgical controls (Sham). Tissue inhibitor of metalloproteinase (TIMPs) play a role in the pathologies of endometriosis. Endometriotic lesions secrete TIMP-1 into the peritoneal fluid of women and rats with endometriosis. We hypothesized endometriotic TIMP-1 contributes to reduced fecundity in endometriosis. Endo rats had fewer ovarian follicles and corpora lutea (CL) and the presence of luteinized unruptured follicles, and fewer oocytes and zygotes which were of poorer quality. Endo rats had reduced fecundity and only Endo rats had miscarriages. Daughters from Endo rats with no surgery had the same reproductive abnormalities which may be caused by an epigenetic factor. Endo rats have more TIMP-1 peritoneal fluid and surrounding follicles than Shams, which may interfere with ovulation. Modulation of TIMP-1 changed the reproductive phenotype. TIMP-1 treated Sham rats had the same reproductive anomalies as Endo rats, while TIMP-1 function blocking antibody treated Endo rats had a fertility phenotype like Sham rats. To test the specificity of TIMP-1 to the mechanism, control rats were treated with peritoneal fluid. Rats treated with Endo peritoneal fluid had reproductive anomalies like Endo rats, but rats treated with Endo peritoneal fluid minus TIMP-1 or Sham fluid did not. Thus, novel therapies modulating TIMP-1 may restore fecundity in women with endometriosis.
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