Developmental Biology

Introduction

The research programme of the Division Developmental Biology can be divided in the following areas: (Epi)genetics, fertility, early development, late development and ethics.

The study of epigenetics is dealing with  the processes that control the use of genetic information  through changing chromatin structure. Central in this approach are the Polycomb Group proteins, a class of epigenetic regulators that control chromatin structure and have been implicated both in normal and abnormal development. Translational reproductive genetic research is aimed at basic as well as applied aspects of pre- and postimplanation development. Human as well as mouse preimplantation embryos are studied to investigate the mechanisms that regulate cell-fate, growth and differentiation. Early development is also studied with respect to in vitro culture of human embryos for IVF and its possible epigenetic effects in the foetus and child. The counterside to early embryonic development (the seed) is the endometrium (the soil). In the latter line of research line factors responsible for successful implantation of the embryo are studied.

The Maastricht group has the only license for preimplantation genetic diagnosis (PGD) in the Netherlands. This has only become possible by combining research with respect to assisted reproduction, which means medically assisted reproduction in the clinical IVF unit with ongoing genetic research and diagnosis. In this program a constant investment in the development of new techniques takes place.

Postnatal studies are concentrating on long term consequences of genetic changes. In this respect special attention is paid to dysmorphology and mental retardation.

Infertility is diagnosed with increasing frequency and has become a major health issue. The research in this area is focused on clinical fertility care as well as advanced (assisted reproduction) treatment options.

In the Ethics programme various normative issues of reproductive medicine are topic of research.

The aim is to stimulate ethical reflection on normative aspects of relevant developments in the clinic and the lab, in order to contribute to adequate guidance, both in the clinic and at the level of society.

“Late development” is related to the development of the fetus in the second half of pregnancy. The program combines basic, translational and clinical research related to the top-clinical functions of neonatal intensive care (NICU) and obstetric high care (OHC), which together form the perinatal center of the MUMC+. The aims are to study the adaptive response and damage/repair mechanisms of the foetus and newborn to a poor pre- and perinatal environment as during severe preeclampsia (asphyxia, hypoxia, growth restriction), chronic intrauterine infections and perinatal insults related to hypoxia and inflammation. The particular emphasis lies on alternations in the developing pulmonary, cardiovascular, and central nervous system that eventually may give rise to long-term morbidity. The latter includes the study of the neurophysiological development and behavioral states (e.g. habitation) in the normal and growth-restricted foetus. As these systems are responsible for most of the morbidity, a better understanding of these mechanisms will help to develop strategies to prevent, or at least minimize, short and long-term sequels.

Several projects focus on lung development and the pathogenesis of chronic lung disease of the newborn. In particular the influence of prenatal inflammation (chorio-amnionitis) on lung development is studied in a newly developed sheep model.

Other projects around developmental vascular biology study the mechanisms of closure of the ductus arteriosus as failure of ductus arteriosus (DA) closure after birth is a common complication of premature delivery with consequences for the developing lung and other organs. Furthermore, studies are performed on  fetal cardiovascular adaptation to hypoxia and its short and long term consequences.

Projects on brain development mainly focus on perinatal asphyxia as this remains a major cause of (severe) brain damage in newborn infants leading to developmental delay or even severe handicaps. New models of perinatal hypoxia were developed in rats with emphasis on the potential protective effect of pre-conditioning by a previous fetal hypoxic period.

The condition and behaviour of the fetus is studied in the last trimester of pregnancy. In recent years the study of fetal memory is one of the main focuses.

European studies have shown that the perinatal mortality in the Netherlandshas decreased less than in most other countries. The underlying problems in the Netherlands are elucidated and new guidelines are formulated. The perinatal research group of the MUMC+ is an active participant in national perinatal research consortium with the aim of improving treatment in the perinatal period.