Assessment of teratogenic influence of metformin on the embryonic development of Anas platyrhynchos

• Main Author: Almarinez, Billy Joel M.
• Format: text
• Published: Animo Repository 2009
• Subjects: Mallard; Embryology; Biology
• Online Access: https://animorepository.dlsu.edu.ph/faculty_research/12066
• Institution: De La Salle University

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by sustained hyperglycemia resulting from impaired glycemic control. Management of hyperglycemia in cases of diabetes mellitus commonly involves insulin therapy or oral pharmacological therapy. Oral hypoglycemic agents are usually more favored by patients over invasive administration of exogenous insulin. Metformin is among the most commonly prescribed hypoglycemic drugs for non-insulin dependent forms of DM. However, this drug is not yet recommended by majority of health authorities for pregnancy-related diabetes. This is due to the insufficiency of evidence pertaining to effects on embryonic development, as metformin is known to cross the placenta. Hence, the current study focused on assessing the teratogenic potential of the drug. An in ovo experiment using the duck (Anas platyrhynchos) embryo as a model was conducted to determine the effects of metformin on embryonic mortality, morphometrics, and pre-hatching and post-hatching weights, as well as to assess the potential of the drug to induce teratologic malformations. In the current study, 0.25 ml of four different concentrations of metformin (ug/ml: 4, 200, 400, 2000) or chick Ringers solution (CRS) was injected into the air cell of viable eggs. Incubation at 37oC was maintained until hatching at 27 days. Effects on mortality, morphometrics, weights, and teratologic incidence in embryos were monitored 7, 9, 12, 15, 20, and 27 days post-incubation. An increasing trend in mortality with higher dosages of metformin was found, although the difference across treatment levels was statistically negligible (a = 0.05). Morphometric measurements and weights were higher in embryos exposed to higher dosages of the drug. Advanced skin development was also noted in metformin-exposed embryos. Vascular anomalies and facial dysmorphogenesis occurred most frequently in some embryos across four dosages of metformin. Isolated cases of microcephaly, forelimb dysmorphogenesis, and ectopia cordis were likewise found only among metformin-exposed embryos. Despite the increase in mortality and incidence of teratologic malformations being statistically negligible, the marked enhancing influence of metformin on growth, and the occurrence of malformations only among metformin-treated embryos suggest the potential of the drug to influence embryonic development.