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Rapid Detection of Neurodevelopmental Phenotypes in Human Neural Precursor Cells (NPCs)
Published on: March 2, 2018
Growth and development in rats given recombinant human epidermal growth factor(1-48) as neonates
J W Henck1, J F Reindel, J A Anderson
1Department of Pathology and Experimental Toxicology, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105, USA. henck_judith_w@lilly.com
Summary
High doses of human recombinant epidermal growth factor (rhEGF(1-48)) accelerated development and altered reflexes in neonatal rats. Some effects, like retinal changes, persisted post-treatment.
Area of Science:
- Developmental Biology
- Pharmacology
- Toxicology
Background:
- Epidermal Growth Factor (EGF) plays a crucial role in cell growth and differentiation.
- Recombinant human EGF (rhEGF) is used therapeutically, necessitating safety assessments.
- Neonatal exposure to growth factors can have profound developmental impacts.
Purpose of the Study:
- To evaluate the effects of supraphysiologic doses of human recombinant epidermal growth factor (1-48) (rhEGF(1-48)) on neonatal Wistar rats.
- To assess the impact on growth, development, reflexes, behavior, and tissue histology.
Main Methods:
- Neonatal rats received daily subcutaneous injections of rhEGF(1-48) (0, 10, 100, or 1000 microg/kg) from postnatal days 1-6.
- Monitoring included clinical signs, body weight, developmental milestones, reflexes, and behavior for 5 weeks.
- Histopathological examination of selected tissues was performed.
Main Results:
- Supraphysiologic rhEGF(1-48) (1000 microg/kg) significantly reduced body weight gain during treatment.
- Precocious development (incisor eruption, eye opening, etc.) occurred at higher doses.
- Delayed reflex acquisition and altered acoustic startle responses were observed, with some effects persisting in females.
- Histological changes, including retinal abnormalities, were noted, with some ocular effects persisting after treatment cessation.
Conclusions:
- Supraphysiologic rhEGF(1-48) administration to neonatal rats causes accelerated development, transient growth suppression, and altered neurobehavioral responses.
- Mitogenic effects on various tissues were observed, consistent with rhEGF(1-48) activity.
- Persistent retinal changes highlight potential long-term risks of high-dose neonatal exposure.
