VALPROIC ACID EFFECT ON BONE MORPHOGENETIC PROTEIN-2 (BMP2) EXPRESSION IN NEURULATION OF MICE (MUS MUSCULUS) EMBRYO STRAIN BALB/C
Valproic acid (VPA) is a drug that is commonly used as a therapeutic agent in patients with epilepsy. Consumption of VPA during the gestational period can increase the risk of neural tube defect (NTD) at a rate of 1-2%. There are several mechanisms of teratogenesis of VPA, one of them is that this c...
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| Format: | Final Project |
| Language: | Indonesia |
| Online Access: | https://digilib.itb.ac.id/gdl/view/78929 |
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| Institution: | Institut Teknologi Bandung |
| Language: | Indonesia |
| Summary: | Valproic acid (VPA) is a drug that is commonly used as a therapeutic agent in patients with epilepsy. Consumption of VPA during the gestational period can increase the risk of neural tube defect (NTD) at a rate of 1-2%. There are several mechanisms of teratogenesis of VPA, one of them is that this compound can act as a histone deacetylase inhibitor (HDACi). Disruption of HDAC enzyme expression can disrupt the expression of bone morphogenetic protein- 2 (BMP2) gene which has a role in determining cell fate, proliferation, and differentiation of cells. Alteration of BMP2 expression can increase the risk of NTD. Pregnant female BALB/c mice were divided into groups of control (K with aquades injection), solvent control (KP with PBS injection), P1 with VPA injection at dose 400 mg/kg body weight (BW), P2 with VPA injection at dose 500 mg/kg BW, P3 with VPA injection at dose 600 mg/kg BW with daily intraperitoneal injection (IP) from 7th day of pregnancy (E7) to 9th day of pregnancy (E9). Mice were sacrificed and dissected at E13, the number of implantations, number of live fetuses, number of resorption, embryos' body weight and crown-rump length (CRL) of embryos as well as the number of embryos with neural tube defect (NTD). Meanwhile, the relative expression of the BMP2 gene was obtained from embryonic neural tissue from embryo E10 with the qRT-PCR method normalized by GAPDH. VPA administration during E7 to E9 did not make a significant difference to the average number of implantations in each treatment. In the reproductive performance of female mice, VPA increased the resorption of embryos and reduced the average body weight and CRL of embryos which gave significantly different results. The injection of VPA has increased the percentage of embryos with NTD, but significant differences are only found at a dose of 600 mg/kg body weight compared to K and KP.
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