Effects of the biguanide class of oral hypoglycemic agents on mouse embryogenesis

摘要: The incidence of birth defects among offspring mothers with non–insulin dependent diabetes mellitus (NIDDM) is 2–3–fold higher than infants non diabetics. Since NIDDM are frequently given oral hypoglycemic agents, including sulphonylureas and biguanides, to control their disease since these agents have been associated the occurrence congenital malformations in humans animals, embryotoxic effects most commonly employed metformin phenformin, were evaluated whole embryo culture. Neurulating mouse embryos exposed therapeutic concentrations (metformin 500–2,550 mg per day; phenformin 50–400 day, respectively) compounds for 24–48 h. Concentrations culture ranged from 0.15 1.8 mg/ml 2.5 × 10−5 0.4 mg/ml. Cultures terminated scored gross morphological alterations total protein content. Metformin produced no embryonic growth major malformations. Approximately 10% all regardless dose, exhibited open cranial neuropores after 24 h However, this anomaly appeared represent a delay closure as opposed an overt defect, highest concentration drug cultured 48 showed neural tubes. In contrast, dose changes malformations, content, embryolethality. Malformations included tube defects, craniofacial hypoplasia, reduction size first second visceral arches. Doses above 0.1 embryolethality killed at concentration. Thus, two biguanides has greater toxicity culture, suggesting that may be safer use during pregnancy. © 1994 Wiley-Liss, Inc.