Int. J. Environ. Res. Public Health 2010, 7 2035 Depletion of the dNTP pool results in the arrest of the cell cycle at the G1 phase prior to DNA synthesis in HIV-infected cell. Incomplete reverse transcription of the viral genome also results from the depletion of dNTP pool [6]. Although HU is an approved drug for the treatment of the above mentioned diseases by the Food and Drug Administration, it poses a risk to the developmental competence of preimplantation embryos because of its anti-mitotic effect. Some teratogenic effects of HU have been observed in fetuses of treated pregnant rodents [8-10], hence the advice to women not to attempt pregnancy while on HU. However, several case reports suggest that HU may have minimal or no teratogenic effects on in vivo exposed developing human fetuses. Fourteen cases of hydroxyurea therapy in pregnant patients with acute or chronic myelogenous leukemia, primary thrombocythemia, or SCD have been reported [11]. 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. The common denominator among the human studies is that they are case studies with limited number of subjects that are not amenable to statistical scrutiny. Besides, it is not known whether the patients took HU as prescribed or when pregnancy ensued. Because HU has antiproliferative properties due to its ability to inhibit DNA synthesis, we believe that it can hinder the active proliferation and growth of preimplantation embryos. The objective of this study was to assess the risks associated with a low clinically relevant dose of HU (30 mg/kg body weight/day; [12]) used for the treatment of SCD, on ovarian function and embryo development, using C57BL/6J strain of female mice as a model. 2. Materials and Methods Animals Adult male and female mice (strain C57BL/6J) 6–8 weeks of age were purchased from Jackson Laboratory (Bar Harbor, ME) and housed by sex (1 male or 4 females/cage) in stainless steel cages and allowed to acclimatize to the Animal Care Facilities for one week prior to initiation of studies. Mice were maintained in an environmentally controlled room with a 14-hour light and 10-hour dark cycle (lights on at 0600h), 22 oC and a humidity range of 50–60%. All animals were allowed ad libitum access to commercial mouse chow and water. Experiment 1 Female mice were randomly assigned to a treatment or a control group (N = 20/group). Treatment consisted of 30 mg HU/kg administered daily by oral gavage for 28 days. The dose of HU used in this study is similar to the daily dose of this drug routinely administered to sickle cell patients [12]. Control mice were administered with the vehicle to this drug (saline) as described above. Five days prior to the cessation of treatments, folliculogenesis was induced in each animal with an IP injection of 5 IU of pregnant mare serum gonadotropin (PMSG) between 1,300 and 1,400 h. Forty eight hours post PMSG, 5 mice/group were anesthetized with isoflurane following which, laparotomy was performed to permit blood collection via the inferior vena cava puncture into serum separation tubes. Sera were separated