Doxycycline inhibits vascular leakage and prevents ovarian hyperstimulation syndrome in a murine model Ofer Fainaru, M.D., Ph.D., Mark D. Hornstein,

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Presentation transcript:

Doxycycline inhibits vascular leakage and prevents ovarian hyperstimulation syndrome in a murine model Ofer Fainaru, M.D., Ph.D., Mark D. Hornstein, M.D., Judah Folkman, M.D. Fertility and Sterility Volume 92, Issue 5, Pages 1701-1705 (November 2009) DOI: 10.1016/j.fertnstert.2008.08.129 Copyright © 2009 American Society for Reproductive Medicine Terms and Conditions

Figure 1 Doxycycline prevents edema and ascites accumulation caused by gonadotropin stimulation. (A) Ovarian hyperstimulation syndrome was induced in female mice (n = 5/group). Designated groups of mice were treated with oral doxycycline (0–40 mg/kg/day) as of day 1 of gonadotropin stimulation. The percentage of weight increase over baseline values is presented (ANOVA, P=.02; Tukey-Kramer HSD, ∗P<.05). (B) In another experiment (n = 5/group) mice were treated with doxycycline (80 mg/kg/day) or vehicle and the volume of peritoneal fluid was determined by Evans blue dye dilution (ANOVA, P=.045; Tukey-Kramer HSD, ∗P<.05). Fertility and Sterility 2009 92, 1701-1705DOI: (10.1016/j.fertnstert.2008.08.129) Copyright © 2009 American Society for Reproductive Medicine Terms and Conditions

Figure 2 Doxycycline prevents peritoneal vessel leakage. Ovarian hyperstimulation syndrome was induced in female mice (n = 5 mice/group). Designated groups of mice were treated with oral doxycycline (0–40 mg/kg/day) as of day 1 of gonadotropin stimulation. (A) Forty-eight hours after hCG administration, Evans blue was injected intravenously. Vascular leakage in the abdominal cavity was analyzed by measuring spectrophotometrically the dye concentration in the fluid retrieved by peritoneal lavage (ANOVA, P=.0072; Tukey-Kramer HSD, ∗P<.05). (B) Ovarian weight from the same mice (ANOVA, P<.0001; Tukey-Kramer HSD, ∗P<.05). Fertility and Sterility 2009 92, 1701-1705DOI: (10.1016/j.fertnstert.2008.08.129) Copyright © 2009 American Society for Reproductive Medicine Terms and Conditions

Figure 3 Doxycycline does not affect ovarian stimulation or angiogenesis. Ovarian hyperstimulation syndrome was induced in female mice (n = 4 mice/group). Designated groups of mice were treated with oral doxycycline (80 mg/kg/day) as of day 1 of gonadotropin stimulation. Histologic sections were prepared from ovaries harvested 48 hours after hCG and stained with H&E; bar = 500 μm (A). The number of corpora lutea (examples designated by red disturbed circle) in ovarian sections with the largest diameter was determined (Student's t test; P=NS) (B). Endothelial cells within the corpora lutea were specifically stained with anti-CD31 antibodies (C). Note the similar microvessel density in both sections; bar = 100 μm. Fertility and Sterility 2009 92, 1701-1705DOI: (10.1016/j.fertnstert.2008.08.129) Copyright © 2009 American Society for Reproductive Medicine Terms and Conditions