Hello Anurag,

The specific genetic background of BALB/c mice makes them particularly vulnerable to VPA's effects. VPA's toxicity disrupts embryonic and placental development, which can lead to complete pregnancy loss. The teratogenic impact of VPA is highly dose dependent. High doses of VPA are generally required to induce the autism-like phenotype, but this also increases the risk and severity of other developmental side effects, including miscarriage. The specific dose and timing of VPA administration are critical variables that can determine the outcome of pregnancy.

To avoid spontaneous miscarriages in your BALB/c mice when developing a VPA-induced autism model, you should,

1. minimize the dose and duration of VPA exposure,

2. optimize the timing of administration for reduced toxicity,

3. ensure thorough VPA treatment adherence to protocol, and

4. consider the use of co-treatments like apigenin or folic acid to mitigate VPA-induced placental and fetal toxicity.

I would recommend starting with a lower dose or gradually increasing the dose. It would help reduce the risk of miscarriage and still achieve the desired autistic phenotype. Regarding the timing of administration, VPA exposure during the first trimester of pregnancy is most likely to result in autism-like symptoms. However, exposure during later periods may also contribute to specific pathologies.

Just a suggest: Since BALB/c mice are particularly susceptible to the effects of VPA, you may use other strains, such as C57BL/6, to observe less severe responses. But the choice of mouse strain will depend on the specific aspect of VPA's effects being studied and the desired level of sensitivity.

Good Luck!