Importance of gestational hypoglycaemia for foetal malformations and skeletal development in rats.
Reprod Toxicol
; 91: 14-26, 2020 01.
Article
in En
| MEDLINE
| ID: mdl-31644949
ABSTRACT
The aim was to investigate embryo-foetal effects of continuous maternal insulin-induced hypoglycaemia extending throughout gestation or until gestation day (GD)17 (typical last day of dosing during pre-clinical evaluation) providing comparator data for safety assessment of longer-acting insulin analogues in non-diabetic rats. Pregnant rats received human insulin (HI)-infusion during gestation until either GD20 or GD17 (HI-GD20; HI-GD17). On GD20, foetal abnormalities and skeletal ossification/mineralisation were evaluated. HI-infusion induced continuous hypoglycaemia. Foetal skeletal and eye malformations (e.g. bent ribs, microphthalmia) were common in both groups. Foetal size and skeletal ossification/mineralisation decreased, particularly with infusion throughout gestation. Concluding, insulin-induced hypoglycaemia during gestation in non-diabetic rats is damaging to embryo-foetal growth and skeletal development, particularly after GD17. Three days without HI-infusion after GD17 allows for some developmental catch-up. Eye development is sensitive to HI-infusion before GD17. These results should serve as a benchmark during pre-clinical safety assessment of longer-acting insulin analogues tested in rats.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bone and Bones
/
Eye Abnormalities
/
Embryonic Development
/
Fetal Development
/
Hypoglycemia
Limits:
Animals
/
Pregnancy
Language:
En
Journal:
Reprod Toxicol
Journal subject:
EMBRIOLOGIA
/
MEDICINA REPRODUTIVA
/
TOXICOLOGIA
Year:
2020
Document type:
Article