Implications for the Conceptus

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Growth and development of the human conceptus occur within the metabolic milieu provided by the mother and are ultimately dependent upon circulating maternal fuels and tissue building blocks. An increasing body of evidence supports the hypothesis that the abnormal gestational environment of the diabetic mother may imprint on certain fetal developing tissues and organs, eventually leading to permanent long-term implications for postnatal function. The fetal tissues most likely to be affected are neural cells, adipocytes, muscle cells and pancreatic b cells. Maternal fuels supply the “building blocks” for fetal development. Freinkel introduced the concept of pregnancy as a “tissue culture experiment”, in which the placenta and the fetus develop in an “incubating medium” totally derived from maternal fuels. All these fuels, glucose, amino acids, lipids, etc., traverse the placenta in a concentration-dependent fashion and thus contribute to the fetal milieu. Since all these constituents are regulated by maternal insulin, disturbances in its supply or actions will influence the whole nutritional content to which the fetus is exposed and, eventually, lead to fetal hyperinsulinaemia. According to Freinkel’s hypothesis, the abnormal maternal mixture of metabolites gains access to the developing fetus in utero, modifying the phenotypic gene expression in newly-formed cells, which in turn may determine permanent, short- and long-term effects in the offspring. Depending upon the time of embryo-fetus exposure to the aberrant fuel mixture, different events may develop.  Early in the first trimester, intrauterine growth retardation and organ malformation, described by Freinkel as “fuel-mediated teratogenesis” may happen. During the second trimester, at the time of brain development and differentiation, behavioural, intellectual or psychological damage may occur. During the third trimester, the abnormal proliferation of fetal adipocytes and muscle cells, together with pancreatic b cells and neuroendocrine cells hyperplasia may be responsible for the development of obesity, hypertension and non-insulin diabetes mellitus later in life.