Assessment of Escherichia coli-derived Recombinant Human Bone Morphogenic Protein-2 on Fertilization and Early Embryonic Development in Rats

• Published in: Pharmaceutical research 2023-06, Vol.40 (6), p.1569-1576
• Main Authors: Kim, Nam Hyun, Min, Seul Ki, Lee, Myeong Wook, Kang, Seung-Hoon
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Body weight; Bone Morphogenetic Protein 2; Bone morphogenetic proteins; E coli; Embryogenesis; Embryonic Development; Escherichia coli; Female; Fertility; Fertilization; Food consumption; Humans; Male; Mating; Medical Law; Menstrual cycle; Necropsy; Original; Original Research Article; Oviduct; Pharmacology/Toxicology; Pharmacy; Pregnancy; Proteins; Rats; Recombinant Proteins; Toxicity
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-023-03514-z

Objective Bone morphogenetic protein-2 (BMP-2) impacts fertility in women by affecting the menstrual cycle and embryonic development. We aimed to determine the reproductive toxicity of Escherichia coli ( E. coli ) - derived recombinant human BMP-2 (rhBMP-2) by measuring changes in the reproductive performance and organs in rhBMP-2-treated rats. Methods Overall, 88 male and female rats each were categorized into one control and three experimental groups. rhBMP-2 was intravenously administered to the experimental groups at 0.05, 0.15, and 0.50 mg/kg/day, respectively. The male rats were administered rhBMP-2 daily, starting from 28 days before mating until the day of necropsy (48 days), after which they were euthanized and necropsied. The female rats were administered rhBMP-2 daily, starting from 14 days before mating until 7 days after fertilization (22–36 days), after which they were necropsied 13 days after fertilization. Results No rhBMP-2-related death occurred throughout the study period. All rhBMP-2-treated groups showed swelling in the tail at the site of rhBMP-2 administration. In the high-dose rhBMP-2 group, the male rats showed a slight reduction in body weight and food consumption, whereas the female rats showed a reduction in the weights of the ovary and oviduct. Examining the fertilization status and necropsy showed no effect of rhBMP-2 on fertility and early embryonic development. The no-observed-adverse-effect level of rhBMP-2 was 0.50 mg/kg/day in all rats. Conclusion rhBMP-2 had no reproductive toxicity on the reproductive performance and organs in female and male rats. Therefore, these results provide new toxicology information on E. coli -derived rhBMP-2 as a therapeutic protein.