Abstract
The placenta is an endocrine fetal organ, which secretes a plethora of steroid- and proteo-hormones, metabolic proteins, growth factors, and cytokines in order to adapt maternal physiology to pregnancy. Central to the growth of the fetus is the supply with nutrients, foremost with glucose. Therefore, during pregnancy, maternal insulin resistance arises, which elevates maternal blood glucose levels, and consequently ensures an adequate glucose supply for the developing fetus. At the same time, maternal β-cell mass and function increase to compensate for the higher insulin demand. These adaptations are also regulated by the endocrine function of the placenta. Excessive insulin resistance or the inability to increase insulin production accordingly disrupts physiological modulation of pregnancy mediated glucose metabolism and may cause maternal gestational diabetes (GDM). A growing body of evidence suggests that this adaptation of maternal glucose metabolism differs between pregnancies carrying a girl vs. pregnancies carrying a boy. Moreover, the risk of developing GDM differs depending on the sex of the fetus. Sex differences in placenta derived hormones and bioactive proteins, which adapt and modulate maternal glucose metabolism, are likely to contribute to this sexual dimorphism. This review provides an overview on the adaptation and maladaptation of maternal glucose metabolism by placenta-derived factors, and highlights sex differences in this regulatory network.
Highlights
For those sections dealing with sex differences, we searched with the combination ‘fetal sex’ or ‘fetal gender’ and ‘maternal insulin resistance’, ‘maternal glucose metabolism’, ‘GDM’ or the name of the corresponding hormone or signal protein
GDM is defined as hyperglycemia first recognized in pregnancy and can be seen as consequence of an insulin supply inadequate to meet the demands for normal blood glucose regulation [14]
The following sections highlight the placenta as an endocrine organ, as well as the hormones, growth factors and metabolically active proteins produced by the placenta, their effects on maternal glucose metabolism, and potential sex differences
Summary
Profound physical, hormonal and humoral changes take place, aiming to allocate essential resources of nutrition for fetal development and the increased maternal demands during pregnancy, delivery and breastfeeding. This unique period of adaptability of the female organism in human reproduction is increasingly acknowledged as a window into the future health of both mother and offspring [1]. One of the most crucial and critical metabolic adjustment is the temporal adaptation of insulin sensitivity and production [2,3] This adaptation of maternal glucose metabolism may in turn affect lipid metabolism and increase oxidative stress levels, if the pregnancy related adaptations exceed normal glucose tolerance [1,2]. In this review we will focus on the adjustment of glucose metabolism in pregnancy
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