A potential role for colony-stimulating factor 1 in the genesis of the early endometriotic lesion.
OBJECTIVE
To investigate the role(s) of colony-stimulating factor 1 (CSF-1) on the development of early endometriosis in a murine model by comparing rate of lesion formation in mice [1] homozygous for a CSF-1 mutation versus syngeneic controls and [2] after treatment with imatinib, a commercially available tyrosine kinase inhibitor that alters interaction(s) between CSF-1 and its receptor, c-fms.


METHODS
Prospective, placebo-controlled animal study.


METHODS
Academic medical center.


METHODS
Six- to 8-week old female FVB, wild-type C57BL/6, and CSF-1 op/op mice.


METHODS
Endometrial tissue from donor mice was used to induce endometriosis in murine recipients. In some experiments, mice homozygous for a CSF-1 mutation (CSF-1 op/op) were donors or recipients. In other experiments, donor and/or recipient mice received imatinib.


METHODS
Histologic confirmation of endometriosis, rate of lesion formation.


RESULTS
By 40 hours, recipient mice developed a mean of 7.2 +/- 0.9 endometriotic lesions that had invaded host surfaces, and mesothelial cells had proliferated over the entire surface of the implants. The CSF-1 op/op mice developed significantly fewer (mean 0.9 +/- 0.3) endometriotic lesions versus syngeneic controls. Imatinib treatment resulted in significantly fewer lesions when compared with sham-treated controls.


CONCLUSIONS
Colony-stimulating factor 1 has a role in establishing early endometriotic lesions. Agents targeting CSF-1 or its actions have therapeutic potential for treating endometriosis.
Jensen
Jani R
JR
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, the University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA. Jensen.jani@mayo.edu
Witz
Craig A
CA
Schenken
Robert S
RS
Tekmal
Rajeshwar R
RR
D000818:Animals; D001549:Benzamides; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004715:Endometriosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D004958:Estradiol / Q000031:analogs & derivatives; D005260:Female; D006720:Homozygote; D000068877:Imatinib Mesylate; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D004958:Estradiol; D016173:Macrophage Colony-Stimulating Factor; D000068877:Imatinib Mesylate; D016186:Receptor, Macrophage Colony-Stimulating Factor