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

Nayak, Guruprasad and Salian, Sujith Raj and Agarwal, Pooja and Poojary, Pooja Suresh and Rao, Arpitha N and Kumari, Sandhya and Kalthur, Sneha Guruprasad and Shreya, Ajjappla B and Mutalik, Srinivas and Adiga, Satish Kumar and Kalthur, Guruprasad (2020) Antidiabetic drug metformin affects the developmental competence of cleavage-stage embryos. Journal of Assisted Reproduction and Genetics, 37. pp. 1227-1238. ISSN 1058-0468

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Abstract

Purpose 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. Methods 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. Results 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. Conclusion The study revealed that metformin affects the early embryonic development and raises concern about its use during conception.

Item Type: Article
Uncontrolled Keywords: Metformin; polycystic ovarian syndrome; blastocyst rate; In vitro maturation.
Subjects: Medicine > KMC Manipal > Anatomy
Medicine > KMC Manipal > Obstetrics & Gynaecology
Pharmacy > MCOPS Manipal > Pharmaceutics
Depositing User: KMC Library
Date Deposited: 09 Oct 2020 05:46
Last Modified: 09 Oct 2020 05:46
URI: http://eprints.manipal.edu/id/eprint/155721

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