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Antidiabetic drug metformin affects the developmental competence of cleavage-stage embryos.

Journal of assisted reproduction and genetics (2020-04-27)
Guruprasad Nayak, Sujith Raj Salian, Pooja Agarwal, Pooja Suresh Poojary, Arpitha Rao, Sandhya Kumari, Sneha Guruprasad Kalthur, Ajjappla B Shreya, Srinivas Mutalik, Satish Kumar Adiga, Guruprasad Kalthur

Metformin is the most commonly prescribed drug in the management of metabolic disorders such as polycystic ovarian syndrome (PCOS) and gestational diabetes in women of reproductive age. Insulin-sensitizing effect of metformin helps in improving from PCOS features such as hyperandrogenism, anovulation, and infertility. However, its ability to cross placental barrier raises concern about safety of the drug on early embryonic development. In this study, we evaluated the effect of metformin on the ovarian function and embryo development. Adult Swiss albino female mice were administered with metformin (0, 50, 100, and 200 mg/kg body weight) for 4 weeks and assessed for reproductive function and preimplantation embryo development. Further, effect of metformin (0, 10, 25, 50, 100, 250, and 500 μg/mL) exposure to 2-cell-stage embryos was tested under in vitro conditions. Metformin did not alter the body weight, blood glucose, ovarian weight, and follicular reserve. However, the early embryo development was significantly affected in mice treated with metformin in vivo at highest dose. Moreover, embryos which were exposed to metformin in vitro showed dose-dependent decline in blastocyst rate and hatching rate. Furthermore, at highest concentration of metformin (500 μg/mL), all the embryos were arrested at compaction stage. The study revealed that metformin affects the early embryonic development and raises concern about its use during conception.

Product Number
Product Description

DAPI, for nucleic acid staining
2′,7′-Dichlorofluorescin diacetate, ≥97%
MEM Non-essential Amino Acid Solution (100×), without L-glutamine, liquid, sterile-filtered, BioReagent, suitable for cell culture
Hyaluronidase from bovine testes, Type IV-S, powder, suitable for mouse embryo cell culture, 750-3000 units/mg solid
1,1-Dimethylbiguanide hydrochloride, 97%
Dulbecco′s Modified Eagle′s Medium - high glucose, With 4500 mg/L glucose and L-glutamine, without sodium bicarbonate, powder, suitable for cell culture