Research profile

Introduction

Sperm are produced in the testis, in the epithelium that lines the seminiferous tubules. This process is called spermatogenesis and can be subdivided into distinct phases. First, there is active proliferation of so-called spermatogonia. A series of divisions is carried out through which millions of cells are formed on a daily basis. The last division of the spermatogonia renders spermatocytes. Spermatocytes carry out the second phase of the spermatogenic process "meiosis". During meiosis homologous chromosomes pair and recombine parental and maternal genes. Subsequently, spermatocytes carry out two divisions leading to the formation of haploid spermatids. During the third phase the spermatids develop from round cells into sperm, a process called spermiogenesis. The spermatogenic process is supported by somatic cells, called Sertoli cells that produce a number of growth factors essential for normal germ cell development. In between the seminiferous tubules there are Leydig cells that produce testosterone which is essential for proper development of spermatocytes and spermatids.

Research lines

- The emphasis of our research has always been on spermatogonial multiplication, especially on the spermatogonial stem cells (SSCs) that are at the basis of the multiplication process ensuring a life-long production of sperm. The SSCs are localized in a stem cell niche in which their maintenance is kept secure. Presently, we are developing a computer model for the behaviour of SSCs in- and outside of their stem cell niche. This niche is important as depletion of SSCs will lead to sterility while too much self-renewal will lead to tumor formation. A better understanding of regulatory processes in the niche may give tools to help particular cases of infertility.

- In collaboration with a group in Rome, attempts are made to improve our understanding of spermatogenesis in humans. In particular, spermatogonial multiplication in primates is different from that in other mammals. In addition, there are some important differences between human and other primates. Using organ donor material, attempts are made to understand spermatogonial multiplication and stem cell renewal in the human. This line of research involves confocal microscopy on human testis samples after staining for various marker proteins and studying BrdU incorporation patterns.

- In collaboration with many groups, the testicular phenotype of a great variety of mutations is studied. The question to be solved here is which cell types are affected and at which step is spermatogenesis arrested. Together these studies provide an inventory of genes that are essential at various developmental steps in the spermatogenic process. Knowledge of the genes that are crucial for a complete spermatogenesis, will be helpful in understanding failure of spermatogenesis in particular cases of male infertility. To that end, testis biopsies of infertile patients are studied as well.

Results

About 300 articles in peer reviewed scientific journals (see Pubmed de Rooij ) and about 50 chapters in Proceedings and Books.

H-index in Google Scholar - 100

Recent Book Chapters / Reviews:  

D.G. de Rooij. 2015. The spermatogonial stem cell niche in mammals. In: Sertoli cell biology. Ed. M.D. Griswold. Elsevier Inc., Amsterdam. Chapter IV. pp. 99-121.

D.G. de Rooij. 2017. Organization of the Seminiferous Epithelium and the Cycle, and Morphometric Description of Spermatogonial Subtypes (Rodents and Primates). In: The Biology of Mammalian Spermatogonia. Eds. J.M. Oatley and M.D. Griswold. Springer, New York, NY. pp. 3-20.

D.G. de Rooij. 2017. The nature and dynamics of spermatogonial stem cells. Development 144, 3022-3030.

G. Hamer, D.G. de Rooij. 2018. Mutations causing specific arrests in the development of mouse primordial germ cells and gonocytes. Biology of Reproduction 99, 75–86.

T. Endo, M.M. Mikedis, P.K. Nicholls, D.C. Page, D.G. de Rooij. 2019. Retinoic acid and germ cell development in the ovary and testis. Biomolecules 9, 775.