Rocca Meredith S, Wehner Nancy G
TherImmune Research Corp., Gaithersburg, Maryland, USA.
Birth Defects Res B Dev Reprod Toxicol. 2009 Apr;86(2):92-7. doi: 10.1002/bdrb.20188.
Regulatory guidelines for developmental and reproductive toxicology (DART) studies require selection of "relevant" animal models as determined by kinetic, pharmacological, and toxicological data. Traditionally, rats, mice, and rabbits are the preferred animal models for these studies. However, for test articles that are pharmacologically inactive in the traditional animal models, the guinea pig may be a viable option. This choice should not be made lightly, as guinea pigs have many disadvantages compared to the traditional species, including limited historical control data, variability in pregnancy rates, small and variable litter size, long gestation, relative maturity at birth, and difficulty in dosing and breeding.
This report describes methods for using guinea pigs in DART studies and provides results of positive and negative controls. Standard study designs and animal husbandry methods were modified to allow mating on the postpartum estrus in fertility studies and were used for producing cohorts of pregnant females for developmental studies.
A positive control study with the pregnancy-disrupting agent mifepristone resulted in the anticipated failure of embryo implantation and supported the use of the guinea pig model. Control data for reproductive endpoints collected from 5 studies are presented.
In cases where the traditional animal models are not relevant, the guinea pig can be used successfully for DART studies.
发育和生殖毒理学（DART）研究的监管指南要求根据动力学、药理学和毒理学数据选择“相关的”动物模型。传统上，大鼠、小鼠和兔子是这些研究的首选动物模型。然而，对于在传统动物模型中无药理活性的受试物，豚鼠可能是一个可行的选择。做出这个选择时不应草率，因为与传统物种相比，豚鼠有许多缺点，包括历史对照数据有限、妊娠率变化大、产仔数少且变化大、妊娠期长、出生时相对成熟，以及给药和繁殖困难。
本报告描述了在DART研究中使用豚鼠的方法，并提供了阳性和阴性对照的结果。对标准研究设计和动物饲养方法进行了修改，以便在生育力研究中使豚鼠在产后发情期交配，并用于为发育研究培育怀孕雌性豚鼠群体。
用妊娠干扰剂米非司酮进行的阳性对照研究导致预期的胚胎着床失败，并支持豚鼠模型的使用。列出了从5项研究中收集的生殖终点对照数据。
在传统动物模型不适用的情况下，豚鼠可成功用于DART研究。
