Effect of a statin on an in vitro model of endometriosis.
OBJECTIVE
To determine the inhibitory effect of a statin on angiogenesis in a three-dimensional (3-D) culture of human endometrial fragments in vitro. Angiogenesis has been proposed as an important mechanism in the pathogenesis of endometriosis, and statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) have been shown to have anti-inflammatory and anti-angiogenic activity.


METHODS
Experimental in vitro study of human endometrial biopsies and 3-D culture in fibrin matrix.


METHODS
Research laboratory at a university-affiliated infertility center.


METHODS
Forty-six normal ovulating women undergoing infertility treatment.


METHODS
Endometrial samples obtained from the fundus of the uterine cavity were minced, and the fragments were placed in a three-dimensional fibrin matrix culture system.


METHODS
Presence or absence of proliferation of stromal cells and invasion of the fibrin matrix, presence or absence of vessel sprouting, and immunohistochemical characterization of cellular components.


RESULTS
During the 1st week of culture, invasion of stromal cells into the fibrin matrix occurred in the control group and in some wells outgrowths were observed. After 2 weeks, endometrial glands were observed in the outgrowths at a distance from the main tissue and were growing in conjunction with new vessel formation until the end of culture period. A concentration-dependent effect of lovostatin was seen on cell growth and angiogenesis in the experimental groups. In the presence of 5 and 10 microM of statin, angiogenesis was abolished, and cell proliferation was inhibited. In the presence of 1 microM of lovastatin, angiogenesis was reduced, but cell proliferation was not affected.


CONCLUSIONS
The statins were shown to be effective in inhibiting the mechanisms of cell proliferation and angiogenesis in an experimental model for the development of endometriosis-like tissue.
Esfandiari
Navid
N
Toronto Centre for Advanced Reproductive Technology, Department of Obstetrics and Gynecology, Division of Reproductive Sciences, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Khazaei
Mozafar
M
Ai
Jafar
J
Bielecki
Ryszard
R
Gotlieb
Lynda
L
Ryan
Edward
E
Casper
Robert F
RF
D000328:Adult; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004715:Endometriosis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D006801:Humans; D008148:Lovastatin / Q000008:administration & dosage*; D009389:Neovascularization, Pathologic / Q000150:complications / Q000473:pathology* / Q000517:prevention & control*
D020533:Angiogenesis Inhibitors; D008148:Lovastatin