Thiazolidinediones decrease vascular endothelial
growth factor (VEGF) production by human luteinized
granulosa cells in vitro
Divya K. Shah, M.D.,a K. M. J. Menon, Ph.D.,a,b Lourdes M. Cabrera, M.S.,a Anjel Vahratian, Ph.D.,
M.P.H.,a Shahryar K. Kavoussi, M.D., M.P.H.,a,c and Dan I. Lebovic, M.D., M.A.d
a Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan; b Department of Biological
Chemistry, University of Michigan, Ann Arbor, Michigan; c Department of Obstetrics and Gynecology, Division of
Reproductive Endocrinology and Infertility, University of Michigan, Ann Arbor, Michigan; and d Department of Obstetrics
and Gynecology, Division of Reproductive Endocrinology and Infertility, University of Wisconsin, Madison, Wisconsin
Objective: To determine the effect of thiazolidenedione derivatives (TZDs) on vascular endothelial growth factor
(VEGF) production by human luteinized granulosa cells and the morphologic development of murine embryos.
Design: Prospective, experimental, in vitro and in vivo study.
Setting: Research laboratory.
Patient(s): Follicular aspirates from 10 women undergoing oocyte retrieval.
Intervention(s): Isolated human granulosa cells were treated with a dimethyl sulfoxide (DMSO) control or ciglitazone,
in the presence and absence of an hCG stimulus. Embryos extracted from superovulated B6C3F1 female
mice were cultured in the presence of DMSO or pioglitazone.
Main Outcome Measure(s): Vascular endothelial growth factor concentrations at 24 and 48 hours. Morphologic
development of murine embryos at 96 hours.
Result(s): Following an hCG stimulus, treatment with 20 mMor 40 mMciglitazone decreased VEGF production in
a statistically significant manner at both time intervals. Blastocyst development at 96 hours did not significantly
differ between untreated zygotes and those treated with pioglitazone.
Conclusion(s): Ciglitazone significantly decreased VEGF production by human granulosa cells in an in vitro
model. Pioglitazone did not adversely impact the development of cultured murine embryos. Although mechanistic
evidence is not provided, the pivotal role of VEGF in ovarian hyperstimulation syndrome prompts investigation of
TZDs as a novel treatment for this condition. (Fertil Steril 2010;93:2042–7. 2010 by American Society for Reproductive
Medicine.)