Bernard Roelen

As a biologist, the beginning of life has always intrigued me

"Life of vertebrates starts as a single cell: the fertilised egg also called zygote. This single cell gives rise to all the different cell types and tissue that compose the fetus and the adult. In placental mammals it even gives rise to the placenta and umbilical cord. The fertilised egg is therefore an extremely, if not the most, powerful and interesting cell!

All cell types
As the embryo develops and differentiates, the cells lose their competence to form different cells types. This is remarkable as each cell maintains a complete genome and therefore the information to form all the different cell types. My lab studies how the egg is being prepared for this important task to make a totipotent zygote, and how the cells of the embryo gradually lose developmental potency while other cells acquire and maintain a level of pluripotency to be able to form the fetus, but not the placenta.

The beginning of life
In short, we study the origin and beginning of life. As a biologist, the beginning of life has always intrigued me. It can be mindboggling to think of the enormous amounts (billions!) of eggs and sperm cells that are made while fusion of only one egg with one sperm cell forms the new embryo. The embryo itself is enormously complex, with different cell types and organs that are formed at the right time and the right place. The embryo is therefore the ideal object to study differentiation and organ formation, and this information can be used for drug development, tissue (re)generation and toxicology studies.

Cattle and pig as model organisms
In order to study mammalian eggs and embryos, we make use of leftover ovaries from slaughterhouses, and in particular bovine and porcine ovaries. These ovaries contain many eggs that we can isolate, culture, and fertilise in the laboratory. The developing embryos can be cultured in vitro for about a week. From dead animals we can make living embryos! As an advantage, this means that we do not have to use laboratory animals. In addition, pigs and cattle are more related to humans than standard model organisms such as the zebrafish and the mouse. Our research therefore not only provides fundamental knowledge but can also help to improve the efficiency of animal and human in vitro fertilisation (IVF).

The gain and loss of pluripotency that occurs in early embryos and during differentiation of tissues is caused by epigenetics: complex changes including DNA methylation and histone modification that affect how cells can read the genes. Although the concept of epigenetics has been around for some time, we are just beginning to understand the components and mechanisms involved. Particularly in germ cells and early embryos the epigenetic landscape is very dynamic. We study how epigenetics helps to protect the integrity of the genome of gametes, but also for instance how the environment can affect the epigenetic topography of early embryos. This helps us to understand (sub)fertility in humans and animals and how the environment can affect disease prevalence already during pregnancy.

Stem cells
The cells that compose the early embryo can be used to derive embryonic pluripotent cells. In addition pluripotent cells can be generated via nuclear reprogramming of adult cells such as skin fibroblasts. At the Faculty of Veterinary Medicine and close to the University Medical Centre Utrecht, we are at the unique position to generate and study stem cells from different animal species including human and cattle to try to understand the mechanisms of cellular potency and cell renewal.