Int. J. Environ. Res. Public Health 2010, 7, 2033-2044; doi:10.3390/ijerph7052033 OPEN ACCESS International Journal of Environmental Research and Public Health ISSN 1660-4601 www.mdpi.com/journal/ijerph Article Perturbation of the Developmental Potential of Preimplantation Mouse Embryos by Hydroxyurea Mariam Sampson, Anthony E. Archibong *, Adriane Powell, Brandon Strange, Shannon Roberson, Edward R. Hills and Phillip Bourne Department of Obstetrics and Gynecology, Meharry Medical College, Nashville, TN 37208-3599, USA; E-Mails: msampson@mmc.edu (M.S.); apowell@mmc.edu (A.P.); bstrange@mmc.edu (B.S.); sroberson@mmc.edu (S.R.); ehills@mmc.edu (E.H.); pbourne@mmc.edu (P.B.) * Author to whom correspondence should be addressed; E-Mail: aarchibong@mmc.edu; Tel.: +1-615-327-5714; Fax: +1-615-327-6296. Received: 8 January 2010; in revised form: 15 January 2010 / Accepted: 3 April 2010 / Published: 28 April 2010 Abstract: Women are advised not to attempt pregnancy while on hydroxyurea (HU) due to the teratogenic effects of this agent, based on results obtained from animal studies. Several case reports suggest that HU may have minimal or no teratogenic effects on the developing human fetus. Fourteen cases of HU therapy in pregnant patients diagnosed with acute or chronic myelogenous leukemia, primary thrombocythemia, or sickle cell disease (SCD) have been reported. Three pregnancies were terminated by elective abortion; 1 woman developed eclampsia and delivered a phenotypically normal stillborn infant. All other patients delivered live, healthy infants without congenital anomalies. We contend that case studies such as these have too few patients and cannot effectively address the adverse effect of HU on preimplantation embryo or fetuses. The objective of this study was to assess the risks associated with a clinically relevant dose of HU used for the treatment of SCD, on ovulation rate and embryo development, using adult C57BL/6J female mice as a model. In Experiment 1, adult female mice were randomly assigned to a treatment or a control group (N = 20/group). Treatment consisted of oral HU (30 mg/kg) for 28 days; while control mice received saline (HU vehicle). Five days to the cessation of HU dosing, all mice were subjected to folliculogenesis induction with pregnant mare serum gonadotropin (PMSG). Five mice/group were anesthetized at 48 hours post PMSG to