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

  • Embryo Biology
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Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

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.

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Funding

This study was funded by Science and Engineering Research Board (SERB), Department of Science and Technology, Government of India, Grant. No. EMR/2016/002077.

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Authors and Affiliations

  1. Department of Clinical Embryology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India

    Guruprasad Nayak, Sujith Raj Salian, Pooja Agarwal, Pooja Suresh Poojary, Arpitha Rao, Sandhya Kumari, Satish Kumar Adiga & Guruprasad Kalthur

  2. Department of Anatomy, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India

    Sneha Guruprasad Kalthur

  3. Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India

    Ajjappla B. Shreya & Srinivas Mutalik

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  1. Guruprasad Nayak
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  2. Sujith Raj Salian
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  3. Pooja Agarwal
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  4. Pooja Suresh Poojary
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  7. Sneha Guruprasad Kalthur
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  8. Ajjappla B. Shreya
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  10. Satish Kumar Adiga
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  11. Guruprasad Kalthur
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Contributions

GN and SRS contributed equally to the manuscript. GN, SRS, PA, PSP, AR, and SK performed experiments; SGK performed histological studies and edited the manuscript; ABS and SM helped in in vitro studies and statistical evaluation of data; SKA edited the manuscript; GK conceptualized and designed the study.

Corresponding author

Correspondence to Guruprasad Kalthur.

Ethics declarations

Animal handling and experimental procedures were done according to the institutional guidelines, and the study protocols were approved by the Institutional Animal Ethics Committee of Kasturba Medical College (IAEC/KMC/25/2014).

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Nayak, G., Salian, S.R., Agarwal, P. et al. Antidiabetic drug metformin affects the developmental competence of cleavage-stage embryos. J Assist Reprod Genet 37, 1227–1238 (2020). https://doi.org/10.1007/s10815-020-01709-6

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