Preliminary Evaluation of a Novel Fetal Guinea Pig Myelomeningocele Model

Abstract

Introduction. Translational models of myelomeningocele (MMC) are needed to test novel in utero interventions. An ideal animal model for MMC has locomotor function at birth and is low cost enough to allow for high throughput. The rat MMC model is limited by immature locomotor function at birth. The ovine MMC model is a costly surgical model. Guinea pigs are uniquely suited for an MMC model being a small animal model with locomotor function at birth. We aimed to develop a retinoic acid (RA) model of MMC in the guinea pig and to evaluate if pregnant guinea pigs could tolerate uterine manipulation. Methods. Time-mated Dunkin Hartley guinea pig dams were dosed with 60 mg/kg of RA between gestation age (GA) 12 and 15 days in the development of an RA model. Fetuses were grossly evaluated for MMC lesions at Cesarean section after GA 31 days. Evaluation of the ability of pregnant guinea pig dams to tolerate uterine surgical intervention was performed by hysterotomy of a separated group of time-mated guinea pigs at GA 45, 50, and 55. Results. Forty-two pregnant guinea pigs were dosed with RA, with a total of 189 fetuses. The fetal demise rate was 38% ( $n=71$ ). A total of 118 fetuses were viable, 83% ( $n=98$ ) were normal fetuses, 8% ( $n=10$ ) had a neural tube defect, and 8% ( $n=10$ ) had a hematoma or other anomalies. No fetuses developed an MMC defect. None of the fetuses that underwent hysterotomy survived to term. Conclusion. RA dosed at 60 mg/kg in guinea pigs between GA 12 and 15 did not result in MMC. Dunkin Hartley guinea pigs did not tolerate a hysterotomy near term in our surgical model. Further work is needed to determine if MMC can be induced in guinea pigs with alternate RA dosing.