Determination of effects of high dose vitamin A on transforming growth factor (TGF-beta) during prenatal term

Type P transforming growth factors (TGF- j3) are a family of polypeptides that regulate cell growth and differentiation, extracellular matrix formation and immun function. Similarly, retinoids are important for multiple physiological proceses such as cell proliferation and differentiation, vision, fertility and embryonic development. The aim of this study was to investigate teratojenic effect of high dose retinoic acid on two different gestational period and interaction between retinoic acid and TGF- |3 during embryonic development. Fifty two adult Wistar female rats used in this study. For mating, female rats were controlled with vaginal smear every morning and was after determination of proeustrus cycle the females were paired 1:1 with male rats. At the next day morning, following the mating procedure was designated gestation day (GD) 0 if sperm was detected in the vaginal smear. Pregnant rats were gavage fed single dose 60 mg/kg body weigth of all-trans retinoic acid (atRA) suspended in olive oil on 8 day or 12 day of gestation. Control animals were given comparable volume of olive oil. Control pregnant rats and pregnant rats retinoic acid administered were killed with cervical dislocation during certain gestational days. Their uteri were removed and the number of implantation and resorption site were recorded. Conceptus were removed from the uterus and weighed and examined for external gross malformations. Then fixed with Bouin's solution and crown-rump length was measured. Data were statistically analysed. Embryos were embeded in paraffin wax and the distribution of TGF- P2 protein in heart and brain tissue was evaluated by irnmunohistochemical staining using the avidin- biotin-peroxidase method.Many malformations including exencephali, exophtalmus, abdominal wall defect, extremity reduction defect, were observed in this experimental study depend on exposured the all-trans retinoic acid at early development period. Using immunohistochemical methods, we determined the expression of TGF- P2 and the effects of retinoic acid on TGF- (52 expression. It was observed that expression of TGF- 132 varies depend on gestation day and effects of retinoic acid. It was observed in this study that fetal brain had immun reaction with TGF- p2. Depend on all-trans retinoic acid, expression of TGF- P2 reduced at gestation day 15, however expression of TGF- J32 was remarkably increased at gestation day 18 by all-trans retinoic acid which was administred at gestation day 8. Retinoic acid, which was administred on gestation day 12, did not have any significant effect on TGF- p2 expression. Fetal brain of these groups immun staining resembled with control groups. TGF- p2 staining in heart tissue particularly restricted with endocardial and pericardial layer except from on gestation day 20. In fetal heart tissue belong to prenatal 20-day fetus showed immune reaction in the miyocardial cells too. But excess retinoic acid lead to decreasing of immune reaction in the heart tissue. As a result, all-trans retinoic acid lead to severe congenital malformtion at early gestational day. Immunohistochemical expression of TGF- (32 was changed depending upon gestation day and effects of all-trans retinoic acid in brain and heart tissues.