Fetal programming in pregnancy-associated disorders: Studies in novel preclinical models

The prenatal period is characterized by rapid growth and development of the fetus.
During this period, organogenesis occurs and maturation of all organs and tissues is accompanied by rapid growth of the body. This is also a very critical period of human’s life because the environment experienced during pregnancy has the ability to shape the physiology of the fetus in order to prepare it for postnatal optimal functioning. Nevertheless, exposure to unfavorable conditions early in life may have long-lasting consequences on the physical and mental health of the offspring. This observation is known as the ‘fetal programming’ paradigm or ‘the Developmental Origins of Health and Disease’ hypothesis.
Throughout pregnancy, the maternal organism goes through local and systemic metabolic, immunological and hemodynamic adaptations that ensure optimal growth and development of the fetus. Failure to achieve optimal nutrient availability or placental functionality will lead to poor growth of the fetus and development of pregnancy-associated disorders. Among the most common pregnancy-associated disorders that contribute to a less optimal in utero development are preeclampsia, intrauterine growth restriction, and gestational diabetes. They are characterized by a complex etiology and can increase the risk of developing other pregnancy-associated disorders. Moreover, the exposed fetus is associated with an increased risk of developing cardiovascular and metabolic diseases in adulthood. However, which gestational factors are involved and to what extent this leads to fetal programming is still widely unknown.
Development of comprehensive preclinical models is of major importance for an evaluation of the effects of gestational factors on fetal programming.In this thesis, we show novel preclinical models for pregnancy-associated disorders
to study the effects of fetal programming due to a non-optimal intrauterine environment.
These models are of extreme importance to unravel the underlying mechanisms which modulate the later health of the offspring. In that way, we can obtain more directions towards the design of proper highly selective and sex-specific diagnostic and therapeutic tools to reverse the fetal programming. The models presented in this thesis recapitulate the clinical course of pregnancy-associated disorders more accurately and aim to bridge the translational research gaps in the fetal programming research.