Christian M. Becker, M. D. , David A. Sampson, B. A. , Maria A

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Presentation transcript:

Endostatin inhibits the growth of endometriotic lesions but does not affect fertility Christian M. Becker, M.D., David A. Sampson, B.A., Maria A. Rupnick, M.D., Richard M. Rohan, Ph.D., Jason A. Efstathiou, M.D., Sarah M. Short, Ph.D., George A. Taylor, M.D., Judah Folkman, M.D., Robert J. D’Amato, M.D. Fertility and Sterility Volume 84, Pages 1144-1155 (October 2005) DOI: 10.1016/j.fertnstert.2005.04.040 Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions

FIGURE 1 Endostatin is biologically active. (A) Human endostatin (hES) significantly inhibits migration of human umbilical vein endothelial cells (HUVEC) at 200 ng/mL in vitro. (B) Human endostatin inhibits growth of BxPC-3 tumors in vivo. Endostatin (red) or vehicle (black) is administered continuously via SC miniosmotic pumps (20 mg/kg) or as daily SC injections (C) (100 mg/kg), compared with controls. Error bars indicate SD; asterisk indicates P<.04. Becker. Endostatin in endometriosis and reproduction. Fertil Steril 2005. Fertility and Sterility 2005 84, 1144-1155DOI: (10.1016/j.fertnstert.2005.04.040) Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions

FIGURE 2 Endostatin inhibits endometriotic lesions. (A) Four weeks of endostatin treatment inhibits growth of surgically induced endometriotic lesions in mice. (B) Growth of established endometriotic lesions is not significantly suppressed by endostatin treatment (black squares: vehicle-treated; gray squares: endostatin-treated). Error bars indicate SD; asterisk indicates P<.001. Becker. Endostatin in endometriosis and reproduction. Fertil Steril 2005. Fertility and Sterility 2005 84, 1144-1155DOI: (10.1016/j.fertnstert.2005.04.040) Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions

FIGURE 3 Endostatin does not affect estrous cycling. (A–D) Methylene blue staining of vaginal smears at different stages of the estrous cycle (clockwise from upper left panel: diestrus (A), proestrus (B), estrus (C), metestrus (D)) Magnification, ×400. (E) Number of full cycles individual mice went through over a period of 2 weeks as determined by daily vaginal smear. Becker. Endostatin in endometriosis and reproduction. Fertil Steril 2005. Fertility and Sterility 2005 84, 1144-1155DOI: (10.1016/j.fertnstert.2005.04.040) Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions

FIGURE 4 Endostatin does not inhibit CL formation. (A) Hematoxylin-eosin staining of a representative ovary found in both endostatin- and vehicle-treated groups. Magnification, ×100. Note two large CL at the right lower end of the ovary (highlighted with arrows and dotted lines). (B) Mean number of CL per tissue section of ovaries in endostatin-treated or vehicle-treated mice. Error bars indicate SD. Becker. Endostatin in endometriosis and reproduction. Fertil Steril 2005. Fertility and Sterility 2005 84, 1144-1155DOI: (10.1016/j.fertnstert.2005.04.040) Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions

FIGURE 5 Endostatin does not negatively influence fertility or pregnancy. Mice were treated either continuously via SC miniosmotic pumps or via daily SC injections. Error bars indicate SD. (A) Mating time. (B) Pregnancy rate. (C) Duration of pregnancy. (D) Litter size (black squares: vehicle-treated mice at ultrasound 2–3 days prepartum; lined squares: control mice at 21 days postpartum; gray squares: endostatin-treated mice at ultrasound 2–3 days prepartum; lined gray squares: endostatin-treated mice 21 days postpartum). Becker. Endostatin in endometriosis and reproduction. Fertil Steril 2005. Fertility and Sterility 2005 84, 1144-1155DOI: (10.1016/j.fertnstert.2005.04.040) Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions