Objectives: To evaluate skeletal developmental defects secondary to chronic valproic acid (VPA) use during pregnancy and the extent of ameliorative effect of combined use of vitamin E and folic acid (FA) during VPA therapy. Materials and Methods: Thirty virgin female albino rats were allowed to get pregnant and were divided into three equal groups: Control group received no medications; VPA group received oral VPA 400 mg/kg body weight (BW) starting on gestational day (GD) 1 till GD20 and Prophylaxis group received oral VPA (400 mg/kg BW) and vitamin E 250 mg/kg BW and folic acid 100 µg/kg BW using gastric tube starting on GD1 till GD20. At GD20, uterine horns were examined for resorption sites, alive or dead fetuses. Extracted living fetuses were examined for BW, crown-rump length (CRL), and antero-posterior (AP) and biparietal diameters and for congenital malformations. Results: VPA significantly reduced all body measurements of living dams compared to control dams. Prophylaxis therapy significantly increased BW, CRL and AP skull diameter compared to VPA dams. The GD20 fetus of VPA group showed delayed ossification of skull bones with wide anterior fontanel (AF) and widely separated parietal bones, very small ossification center (OC) for hyoid bone. Caudal vertebrae were unossified or showed very small OC with no evident OC for calcaneous, metatarsal bones or distal phalanges. Fetuses of prophylaxis group showed slightly wide AF than that of control animals and parietal bones are separated to lesser extent than VPA group. Mandible is developed, with an OC for hyoid bone and sternebrae are seen. Six caudal vertebrae and few OC in phalanges are seen, but no OC in calcaneous. Conclusion: VPA chronic administration during pregnancy showed deleterious effects on fetal body measurements and skeletal system development. Concomitant administration of vitamin E and FA significantly ameliorated these changes.

Background: Bisphenol A (BPA) is a synthetic estrogen that predisposes to prostate disease. Indole-3-carbinol (I 3 C), found in vegetables, has chemo-protective properties in hormone dependent cells. This work investigates the harmful effect of prenatal exposure to BPA on rat prostate and the protective effect of I3C. Material& methods: 30 pregnant albino rats were divided equally into 3 groups: 1-Control group: received no medication. 2-Bisphenol group: received 25 μg BPA / kg body weight (BW), orally by gavage once daily from 8 th day of pregnancy to day 21. 3-Bisphenol and indole group: received 25 μg BPA / kg BW, orally by gavage once daily plus 2 g I 3 C/kg chow, from 8 th day of pregnancy to day 21. The prostates were collected from male offspring at 1 and 3 months after birth and were examined by light and electron microscopes. Results:The prostates from bisphenol group showed epithelial hyperplasia, increased intraluminal papillary projections and inflammatory cells in the interstitial space. The acinar cells presented heterochromatic irregular nuclei, vacuolated mitochondria and degenerated microvilli. Multiple layers of fibroblasts accumulate outside the basement membrane. The prostates from bisphenol and indole group showed a nearly intact simple columnar epithelial lining of the acini with basal rounded nuclei, normal mitochondria and intact apical microvilli.Conclusion: Prenatal exposure to BPA has a harmful effect on prostate. Maternal I3C feeding during pregnancy has a protective effect against the gestational BPA harmful imprinting on the prostate.