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

Nayak, Guruprasad; Salian, Sujith Raj; Agarwal, Pooja; Poojary, Pooja Suresh; Rao, Arpitha; Kumari, Sandhya; Kalthur, Sneha Guruprasad; Shreya, Ajjappla Basavaraj; Mutalik, Srinivas; Adiga, Satish Kumar; Kalthur, Guruprasad

doi:10.1007/s10815-020-01709-6

Cited by 6 publications

(4 citation statements)

References 58 publications

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“…However, more recent studies using mice have shown that metformin can affect early embryonic development, especially at higher doses. ( 63 ). No robust data regarding fetal malformations in humans exposed to metformin have been described thus far.…”

Section: Methodsmentioning

confidence: 99%

Glycemic and nonglycemic mechanisms of congenital malformations in hyperglycemic pregnancies: a narrative review

Negrato¹,

Marques²,

Leite³

et al. 2022

Archives of Endocrinology and Metabolism

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Congenital malformations are more frequently found among children born to mothers with diabetes than in the background population. There are several complex mechanisms involved in the development of congenital malformations in the offspring of mothers with hyperglycemia, such as the overexpression of glucose transporters (GLUTs) 1 and 2, the increased activity of the hexosamine biosynthetic pathway and the reduced expression of the PAX3 gene with a consequent increase in p53 protein expression. These alterations can lead to increased glucose and free radical concentrations in the embryo, thus promoting the process of apoptosis and causing malformation. The most frequent malformations found in the offspring of mothers with diabetes are heart and neural tube defects, urinary tract and kidney malformations, and cleft lip with or without cleft palate. Strict glycemic control should be obtained before and during pregnancy, aiming to avoid or minimize the risk of congenital malformations in the offspring. Beyond hyperglycemia, several factors may also be associated with increased risks of malformations in the offspring of these women, such as obesity, multiple pregnancies, advanced maternal age, folic acid deficiency, use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers, assisted reproduction techniques, and exposure to different types of environmental pollutants.

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Section: Methodsmentioning

confidence: 99%

Glycemic and nonglycemic mechanisms of congenital malformations in hyperglycemic pregnancies: a narrative review

Negrato¹,

Marques²,

Leite³

et al. 2022

Archives of Endocrinology and Metabolism

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“…However, there might be some adverse effects on the fetus. Nayak et al shed that metformin affects the developmental competence of cleavage-stage embryos [72]. Another study by Faure et al suggests intrauterine exposure to metformin reduces the fertility of male offspring in adulthood [73].…”

Section: Treatmentmentioning

confidence: 99%

Gestational Diabetes and Infertility

Turan¹,

Delibaşı²

2023

JDM

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Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications which affect the mother and offspring. In addition to adverse perinatal outcomes, it may lead to permanent health problems for the mother, such as type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD), while increasing the risk of future obesity, CVD, T2DM and GDM in the child. Approximately 15% of women seek fertility treatment. Over the last decade, it has come to attention that patients with an infertility history are more prone to having GDM during their pregnancies, and this review examines the relationship between GDM and infertility. The elevated estrogen, progesterone, leptin, placental lactogen and growth hormone are the main reasons for increased insulin resistance during pregnancy. Despite some confounding factors in the mechanism of GDM in patients with an infertility history, infertility treatment increases the risk, according to numerous studies. The obesity epidemic and associated disorders have become a significant public health concern worldwide. Lifestyle modification for weight loss before pregnancy is encouraged, but there is no strong evidence for improvement in perinatal results. GDM, infertility and infertility treatment have a potential risk of alteration in the embryo's environment and cause epigenetic reprogramming, which may be inherited to the next generation. The fertility treatment impacts the patient's and offspring's health. Patients should be informed about the risks so that they consent and get involved in the decision. Infertility treatment may be accepted as a reason for high-risk pregnancy, and patients can be screened for GDM in early pregnancy.

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“…Interestingly, although in a very critical assessment of metanalyses regarding MTF, most were deemed to be of low quality, the exception being those in obstetric/gynecological settings [ 42 ]. There are caveats in the use of MTF in pregnancy: it was found—in vitro, in human embryonic stem cells—to decrease the differentiation of pancreatic beta cells [ 43 ], and in mice to decrease or arrest early embryonic development [ 44 ].…”

Section: Gender-specific Use Of Mtfmentioning

confidence: 99%

Metformin: Sex/Gender Differences in Its Uses and Effects—Narrative Review

Ilias¹,

Rizzo

Zabulienė

2022

Medicina

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Metformin (MTF) occupies a major and fundamental position in the therapeutic management of type 2 diabetes mellitus (T2DM). Gender differences in some effects and actions of MTF have been reported. Women are usually prescribed lower MTF doses compared to men and report more gastrointestinal side effects. The incidence of cardiovascular events in women on MTF has been found to be lower to that of men on MTF. Despite some promising results with MTF regarding pregnancy rates in women with PCOS, the management of gestational diabetes, cancer prevention or adjunctive cancer treatment and COVID-19, most robust meta-analyses have yet to confirm such beneficial effects.

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

Cited by 6 publications

References 58 publications

Glycemic and nonglycemic mechanisms of congenital malformations in hyperglycemic pregnancies: a narrative review

Glycemic and nonglycemic mechanisms of congenital malformations in hyperglycemic pregnancies: a narrative review

Gestational Diabetes and Infertility

Metformin: Sex/Gender Differences in Its Uses and Effects—Narrative Review

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