A shortened study design for embryo-fetal development studies in the minipig

Area of Science:

• Toxicology
• Developmental Biology
• Preclinical Research

Background:

• Minipigs are valuable models for drug safety evaluation of embryo-fetal development.
• Their large size and long gestation period (112-115 days) present challenges in study duration and cost-effectiveness.
• Optimizing study timelines is crucial for efficient drug development.

Purpose of the Study:

• To evaluate the feasibility of optimizing study duration and cost in minipig embryo-fetal development studies.
• To assess scientific validity when performing terminal procedures at mid-gestation (60 days) instead of at term.
• To determine if mid-gestation assessments are suitable for detecting developmental abnormalities.

Main Methods:

• Minipig studies were conducted with terminal procedures performed at mid-gestation (60 days).
• Fetal size at mid-gestation was compared to full-term rabbit fetuses for suitability of examination.
• A known teratogen, pyrimethamine, was administered to assess detection of morphological defects.
• Histological examination of gonads and double staining of fetal skeletons were employed for detailed analysis.

Main Results:

• Despite higher embryo-fetal death rates, morphological defects consistent with pyrimethamine exposure were identified.
• External sexing of fetuses at mid-gestation was confirmed accurate via histological examination of gonads.
• Double staining facilitated a more refined examination of the mid-term fetal skeletal development.

Conclusions:

• Performing terminal procedures at mid-gestation in minipigs is a viable strategy to optimize study duration and cost.
• This mid-gestation approach maintains scientific validity for detecting teratogenic effects.
• Mid-gestation assessment, including histological and skeletal analysis, provides robust data for embryo-fetal safety evaluations.