Endostatin inhibits the growth of endometriotic lesions but does not affect fertility.
OBJECTIVE
To determine whether endometriosis can be treated with the angiogenesis inhibitor endostatin and the effect of this treatment on fertility and reproduction.


METHODS
Pharmacologic intervention in a surgically induced model of endometriosis and in female mice undergoing mating.


METHODS
Animal research facility.


METHODS
Eight-week-old, female C57BL/6 and SCID mice.


METHODS
After implantation of autologous endometrium, mice received endostatin or the vehicle-matched control for 4 weeks. For the reproductive function study, mice receiving endostatin or vehicle were mated and reproductive functions were observed.


METHODS
Growth of endometriotic lesions after 4 weeks of treatment; estrous cycling, corpus luteum formation, serum hormone levels, and mating time as fertility measures; and pregnancy rates, length of pregnancy, fetal vitality, number, and outcome of litter as reproductive measures.


RESULTS
Endostatin suppressed the growth of endometriotic lesions by 47% compared with controls. Estrous cycling and corpus luteum formation were normal in both groups. Female mice receiving endostatin were as fertile as mice receiving vehicle, had normal pregnancies, and delivered the same number of pups. The offspring were healthy without teratogenic stigmata and reproduced normally themselves.


CONCLUSIONS
Antiangiogenic therapy with endostatin may present a promising novel, nontoxic therapeutic option for patients with endometriosis.
Becker
Christian M
CM
Department of Surgery, Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Sampson
David A
DA
Rupnick
Maria A
MA
Rohan
Richard M
RM
Efstathiou
Jason A
JA
Short
Sarah M
SM
Taylor
George A
GA
Folkman
Judah
J
D'Amato
Robert J
RJ
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D045744:Cell Line, Tumor; D004715:Endometriosis / Q000188:drug therapy* / Q000473:pathology*; D043169:Endostatins / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005298:Fertility / Q000187:drug effects* / Q000502:physiology; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D011247:Pregnancy
D020533:Angiogenesis Inhibitors; D043169:Endostatins; D006131:Growth Inhibitors