mercaptopurine and Fetal-Growth-Retardation

In order to investigate the effect of placental size on fetal intrauterine growth retardation (IURG), we examined the morphology and alterations in the expression of glucose transporter in the placentas of rats exposed to 6-mercaptopurine (6-MP). 6-MP was administered orally at 0 and 60 mg/kg/day on gestation day (GD) 9, 11, 13 or 15, and the placentas were sampled on GDs 17 and 21. The main findings in the treated groups were small placenta caused by mitotic inhibition and apoptosis, fetal resorption and IUGR with or without some malformations. The most sensitive period to 6-MP-induced fetal mortality was found to be in the GD9-treated group, and the small placenta and fetal abnormalities in the GD11-treated group, respectively. However, the litters in a quarter of the dams with the treatment on GD 11 had no fetotoxicity despite 25% decline in the placental weight. Histopathologically, the expression of glucose transporter GLUT3 was increased in the trophoblastic septa in all treated groups, particularly remarkable with proliferation of trophoblasts in the above litters, where the fetal-placental weight ratio was increased. Thus, we consider that the normal fetal growth and development can be maintained caused by adaptive change, even if the placental weight decreased by approximately 25% in 6-MP exposed rats.

Topics: Abnormalities, Drug-Induced; Animals; Apoptosis; Female; Fetal Death; Fetal Growth Retardation; Fetal Weight; Gestational Age; Glucose Transport Proteins, Facilitative; Mercaptopurine; Organ Size; Placenta; Pregnancy; Rats; Rats, Inbred Strains; Teratogens

This report documents the acute toxicity of anti-leukemic chemotherapy on the fetus in utero by umbilical blood sampling. A patient with acute myelocytic leukemia diagnosed at the 23rd week of gestation received combination chemotherapy, and carried the pregnancy to successful delivery at the 34th week. During the course of pregnancy, the fetal condition was evaluated by serial real time sonograms and umbilical blood sampling through cordocentesis. Fetal hematopoiesis was preserved against maternal chemotherapeutic agents, and no developmental abnormalities were observed. This is the first attempt to evaluate the acute effects of chemotherapeutic agents on the fetus in utero by real time umbilical cord sampling.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Female; Fetal Blood; Fetal Growth Retardation; Fetus; Humans; Infant, Newborn; Leukemia, Myeloid, Acute; Mercaptopurine; Prednisolone; Pregnancy; Pregnancy Complications, Neoplastic; Ultrasonography, Prenatal