The Effects of Maternal Metformin Treatment on Late Prenatal and Early Postnatal Development of the Offspring Are Modulated by Sex.

Consolacion Garcia-Contreras,Susana Astiz,Antonio Gonzalez-Bulnes,Marta Vazquez-Gomez,Ana Heras-Molina,Teresa Encinas,José Pesantez-Pacheco

doi:10.3390/ph13110363

Consolacion Garcia-Contreras, Susana Astiz + Show 5 more

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https://doi.org/10.3390/ph13110363

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Journal: Pharmaceuticals	Publication Date: Nov 4, 2020
Citations: 7	License type: CC BY 4.0

Affiliation: University of A Coruña

Abstract

Metformin is currently used to improve pregnancy outcome in women affected by polycystic ovary syndrome (PCOS) or diabetes. However, metformin may also be useful in pregnancies at risk of intrauterine growth restriction (IUGR) since it improves placental efficiency and the fetuses’ developmental competence. There is no data on the duration of the effect of this treatment from the prenatal up to the postnatal stages. Therefore, the present trial aimed at determining the impact of metformin treatment on the offspring neonatal traits and early postnatal development (i.e., during lactation) using an in vivo swine model. The results support that maternal metformin treatment during pregnancy induces protective changes in body shape and composition of the progeny (i.e., larger head size and body length at birth and higher total viscera weight at weaning). However, there were also major effects of the offspring sex (smaller corpulence in females and lower relative weight of main viscerae in males), which should be considered for further preclinical studies and when even the current clinical application in women affected by PCOS or diabetes is implemented.

Highlights

Intrauterine growth restriction (IUGR), the failure of a fetus to reach its full genetic growth potential, affects between 6% and 17% of total human pregnancies; a range depending on environmental and socioeconomic factors
Maternal metformin treatment during pregnancy did not induce significant differences in birthweight but in body shape, to our previous study performed during the last days of pregnancy [15]
Offspring from metformin-treated pregnancies had significantly higher values for head size and body length. These results are highly interesting since recent studies addressed that head profile and body shape at birth are more predictive of the postnatal development in SGA piglets than the proper birthweight [17,18]

Summary

Introduction

Intrauterine growth restriction (IUGR), the failure of a fetus to reach its full genetic growth potential, affects between 6% and 17% of total human pregnancies; a range depending on environmental and socioeconomic factors. The term “placental insufficiency” defines a deficiency in the placental development and function, causing a shortage of the transfer of nutrients and oxygen to the fetus. This condition is currently estimated to be the cause of around 60% of IUGR cases [4]. Placental insufficiency is a rising problem, since it is linked to many contemporary factors (delay in childbearing age, inadequate lifestyle, stress, sedentarism, pollution, alcohol and tobacco intake, obesity, diabetes or preeclampsia [5])

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