Cargando…

Preliminary Evaluation of a Novel Fetal Guinea Pig Myelomeningocele Model

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 o...

Descripción completa

Detalles Bibliográficos
Autores principales: Stokes, Sarah C., Yamashiro, Kaeli J., Vanover, Melissa A., Galganski, Laura A., Jackson, Jordan E., Theodorou, Christina M., Pivetti, Christopher D., Farmer, Diana Lee, Wang, Aijun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378975/
https://www.ncbi.nlm.nih.gov/pubmed/34423032
http://dx.doi.org/10.1155/2021/2180883
_version_ 1783740913187553280
author Stokes, Sarah C.
Yamashiro, Kaeli J.
Vanover, Melissa A.
Galganski, Laura A.
Jackson, Jordan E.
Theodorou, Christina M.
Pivetti, Christopher D.
Farmer, Diana Lee
Wang, Aijun
author_facet Stokes, Sarah C.
Yamashiro, Kaeli J.
Vanover, Melissa A.
Galganski, Laura A.
Jackson, Jordan E.
Theodorou, Christina M.
Pivetti, Christopher D.
Farmer, Diana Lee
Wang, Aijun
author_sort Stokes, Sarah C.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8378975
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-83789752021-08-21 Preliminary Evaluation of a Novel Fetal Guinea Pig Myelomeningocele Model Stokes, Sarah C. Yamashiro, Kaeli J. Vanover, Melissa A. Galganski, Laura A. Jackson, Jordan E. Theodorou, Christina M. Pivetti, Christopher D. Farmer, Diana Lee Wang, Aijun Biomed Res Int Research Article 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. Hindawi 2021-08-13 /pmc/articles/PMC8378975/ /pubmed/34423032 http://dx.doi.org/10.1155/2021/2180883 Text en Copyright © 2021 Sarah C. Stokes et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Stokes, Sarah C.
Yamashiro, Kaeli J.
Vanover, Melissa A.
Galganski, Laura A.
Jackson, Jordan E.
Theodorou, Christina M.
Pivetti, Christopher D.
Farmer, Diana Lee
Wang, Aijun
Preliminary Evaluation of a Novel Fetal Guinea Pig Myelomeningocele Model
title Preliminary Evaluation of a Novel Fetal Guinea Pig Myelomeningocele Model
title_full Preliminary Evaluation of a Novel Fetal Guinea Pig Myelomeningocele Model
title_fullStr Preliminary Evaluation of a Novel Fetal Guinea Pig Myelomeningocele Model
title_full_unstemmed Preliminary Evaluation of a Novel Fetal Guinea Pig Myelomeningocele Model
title_short Preliminary Evaluation of a Novel Fetal Guinea Pig Myelomeningocele Model
title_sort preliminary evaluation of a novel fetal guinea pig myelomeningocele model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378975/
https://www.ncbi.nlm.nih.gov/pubmed/34423032
http://dx.doi.org/10.1155/2021/2180883
work_keys_str_mv AT stokessarahc preliminaryevaluationofanovelfetalguineapigmyelomeningocelemodel
AT yamashirokaelij preliminaryevaluationofanovelfetalguineapigmyelomeningocelemodel
AT vanovermelissaa preliminaryevaluationofanovelfetalguineapigmyelomeningocelemodel
AT galganskilauraa preliminaryevaluationofanovelfetalguineapigmyelomeningocelemodel
AT jacksonjordane preliminaryevaluationofanovelfetalguineapigmyelomeningocelemodel
AT theodorouchristinam preliminaryevaluationofanovelfetalguineapigmyelomeningocelemodel
AT pivettichristopherd preliminaryevaluationofanovelfetalguineapigmyelomeningocelemodel
AT farmerdianalee preliminaryevaluationofanovelfetalguineapigmyelomeningocelemodel
AT wangaijun preliminaryevaluationofanovelfetalguineapigmyelomeningocelemodel