Submission Number: ADR-4-99-124

Abstract Number: 194

EFFECT OF HYDROXYUREA (HU) ON OVARIAN RESPONSE TO GONADOTROPINS AND SUBSEQUENT DEVELOPMENT OF GENERATED EMBRYOS.

AR Powell*, C Palmer*, B Strange*, A Okibedi* and AE Archibong*

Department of Obstetrics and Gynecology, Meharry Medical College, Nashville, TN ¹

Abstract:
The purpose of this study was to investigate the effect of HU on ovarian response to gonadotropins and the subsequent development of generated embryos in vitro. 21d old female mice (strain C57BL/6J;N=20) were injected IP with 30mg/kg of HU (dose given to sickle cell patients) daily for 28 days. Control animals were similarly injected with vehicle, saline (N=20). 4 days prior to cessation of HU treatment, folliculogenesis was induced in each animal with 2.5 IU PMSG. 48 hr post-PMSG, ovulation was induced with 2.5 IU hCG. Females were thereafter mated to adult males of similar strain. 36 hr post-hCG, females were sacrificed, ovaries excised and weighed, and oviducts removed and flushed with Whitten's medium (WM) for embryo recovery. Number of embryos flushed was determined, and normal 2-cell embryos were subjected to in vitro culture by treatment, in WM enriched with CZBt for 5 days. Data on ovarian wt and ovulation rate were analyzed by one-way analysis of variance, while data on embryo development were analyzed by Chi-square. Treated animals sustained a decrease in ovarian wt as compared with controls (control, 0.02004; HU, 0.01004; P<0.05; N =5/treatment group). Ovulation rate (N = 5; 72.5) was also reduced compared with controls (N = 5; 13.41.6), but the difference was not statistically significant. 2-cell embryos recovered from HU-treated females developed poorly to blastocysts in vitro compared with those from controls (HU, 66%; control, 94%). Though HU is a beneficial drug for the alleviation of the clinical manifestations of sickle cell disease, it compromises ovarian physiology and ability of generated embryos to develop to blastocysts.

Keywords: Toxicology, ovary

This abstract is being presented at: 8:00 AM in session:
Toxicology I