Abstract

The first three months of human pregnancy is a critical period. The conceptus implants into the wall of the uterus, and interacts with the maternal tissues to form the placenta that will supply the embryo with nutrients. Meanwhile, the main organ systems in the embryo differentiate. Many conceptions are lost before 12 weeks of pregnancy, but then the rate falls dramatically. Over the last few years we have demonstrated that the intrauterine environment is unique compared to the remainder of pregnancy. Most importantly, we have shown that the conceptus derives its nutrients not from the maternal blood as has always been believed, but from the secretions of the endometrial glands, the ‘uterine milk’. This confers the major advantage that the embryo develops in a low oxygen environment, which protects it from oxidative-mediated teratogenesis. This paradigm shift in our understanding of the physiology of early pregnancy has profound implications for basic and translational research. For example, it requires us to revaluate the delivery of key micronutrients, such as folate, when the neural tube and other organ systems are forming. The shift has also provided important new insights into the pathological basis of miscarriage and complications of later pregnancy, centred around placental oxidative stress. These insights open new avenues for research into diagnostic biomarkers and potential therapeutic interventions.