Fetal programming in pregnancy-associated disorders

Fetal programming in pregnancy-associated disorders

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 isaccompanied by rapid growth of the body. This is also a very critical period of human’s lifebecause the environment experienced during pregnancy has the ability to shape thephysiology 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 thephysical and mental health of the offspring. This observation is known as the ‘fetalprogramming’ paradigm or ‘the Developmental Origins of Health and Disease’ hypothesis.Throughout pregnancy, the maternal organism goes through local and systemicmetabolic, immunological and hemodynamic adaptations that ensure optimal growth anddevelopment of the fetus. Failure to achieve optimal nutrient availability or placentalfunctionality will lead to poor growth of the fetus and development of pregnancy-associateddisorders. Among the most common pregnancy-associated disorders that contribute to a lessoptimal in utero development are preeclampsia, intrauterine growth restriction, andgestational diabetes. They are characterized by a complex etiology and can increase the riskof developing other pregnancy-associated disorders. Moreover, the exposed fetus isassociated with an increased risk of developing cardiovascular and metabolic diseases inadulthood. However, which gestational factors are involved and to what extent this leads tofetal programming is still widely unknown.Development of comprehensive preclinical models is of major importance for anevaluation of the effects of gestational factors on fetal programming.In this thesis, we show novel preclinical models for pregnancy-associated disordersto study the effects of fetal programming due to a non-optimal intrauterine environment.These models are of extreme importance to unravel the underlying mechanisms whichmodulate the later health of the offspring. In that way, we can obtain more directions towardsthe design of proper highly selective and sex-specific diagnostic and therapeutic tools toreverse the fetal programming. The models presented in this thesis recapitulate the clinicalcourse of pregnancy-associated disorders more accurately and aim to bridge the translationalresearch gaps in the fetal programming research.

Dissertation: http://hdl.handle.net/11370/610fdbdd-7917-47b1-b7da-6a8e266b0887