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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抗糖尿病药物二甲双胍会影响卵裂期胚胎的发育能力。

目的二甲双胍是育龄妇女在代谢性疾病（如多囊卵巢综合症（PCOS）和妊娠糖尿病）治疗中最常用的处方药。二甲双胍对胰岛素的增敏作用有助于改善PCOS功能，例如雄激素过多，无排卵和不育。然而，其穿越胎盘屏障的能力引起人们对该药物对早期胚胎发育的安全性的关注。在这项研究中，我们评估了二甲双胍对卵巢功能和胚胎发育的影响。方法给成年瑞士白化病雌性小鼠服用二甲双胍（0、50、100和200 mg / kg体重），持续4周，并评估其生殖功能和植入前胚胎的发育。此外，二甲双胍（0，10，25，50，100，250，在体外条件下测试了500μg/ mL和500μg/ mL）暴露于2细胞阶段胚胎的情况。结果二甲双胍未改变体重，血糖，卵巢重量和卵泡储备。但是，在最高剂量的体内用二甲双胍治疗的小鼠中，早期胚胎发育受到显着影响。此外，体外暴露于二甲双胍的胚胎在胚泡率和孵化率上呈剂量依赖性下降。此外，在最高浓度的二甲双胍（500μg/ mL）下，所有胚胎均在压实阶段被捕杀。结论该研究表明二甲双胍会影响早期胚胎发育，并引起人们对其在受孕过程中使用的担忧。在最高剂量的体内用二甲双胍治疗的小鼠中，早期胚胎发育受到显着影响。此外，体外暴露于二甲双胍的胚胎在胚泡率和孵化率上呈剂量依赖性下降。此外，在最高浓度的二甲双胍（500μg/ mL）下，所有胚胎均在压实阶段被捕杀。结论该研究表明二甲双胍会影响早期胚胎发育，并引起人们对其在受孕过程中使用的担忧。在最高剂量的体内用二甲双胍治疗的小鼠中，早期胚胎发育受到显着影响。此外，体外暴露于二甲双胍的胚胎在胚泡率和孵化率上呈剂量依赖性下降。此外，在最高浓度的二甲双胍（500μg/ mL）下，所有胚胎均在压实阶段被捕杀。结论该研究表明二甲双胍会影响早期胚胎发育，并引起人们对其在受孕过程中使用的担忧。