Developmental Biology

Reproductive Biology Lab

Welcome to the reproductive biology lab

Dr. Rüdiger Schulz and Dr. Jan Bogerd

Reproduction is one of the major biological processes characteristic of all living species. In animals, sexual reproduction is the by far dominating mode of reproduction, although only half of the individuals (i.e. mothers) can produce offspring. The balance of this costly strategy is provided by the evolutionary advantage of the genetic recombination shuffle during meiosis in combination with sexual selection that exerts its pressure predominantly on males, the gender often providing little to the next generation beyond genes. The power of sexual selection is exemplified by extravagant traits for male-male competition in some species. Seemingly wasteful, these traits reflect the male’s competence to recruit resources from the environment and thus involve several genes spread over the genome. Females make use of these indicators of genome quality during mate choice.

Research details

Introduction

Sexual reproduction requires the sexual interaction of two specialized reproductive cells, called gametes. Gametes are produced in a process named gametogenesis through meiosis from immature germ cells in organs called gonads (testis in males and ovaries in females). In this way, the testes produce spermatozoa in a developmental process named spermatogenesis from the male's immature germ cells or spermatogonia. Similarly, ovaries produce ova in a developmental process named oogenesis from the female’s immature germ cells or oogonia. Irrespective of the stage of development, germ cells cannot survive in the gonads unless they receive support from and are in physical contact with a somatic cell type, known as Sertoli cells in males and granulosa cells in females. The latter two cell types are important targets of hormones regulating gametogenesis: Fsh produced in the pituitary as well as sex steroid hormones produced by the gonads (e.g. Leydig cells in the testis and theca cells in the ovaries).

Basic research question

Our research has focused on the question, “How do hormones and growth factors regulate the proliferation and differentiation behavior of germ cells, in particular of spermatogonial stem cells?” Moreover, we studied the production and release of hormones and growth factors regulating spermatogenesis, in particular Fsh. We have concentrated on four aspects:

  1. Identify candidate growth factors relevant for spermatogenesis via gene expression profiling (e.g., microarray; RNAseq [mRNA, miRNA, lncRNA]).
  2. Characterize the biological activity of identified candidate factors by expression profiling (RNAseq), loss-of-function as well as gain-of-function approaches. The functional approaches often use a primary testis tissue culture system for pharmacological approaches, or for testing recombinant hormones/growth factors; we also use genetic models, such as CRISPR/Cas-mediated gene knock out as well as transgenesis models.
  3. Study the endocrine regulation of expression and/or release of identified candidate factors.
  4. Examine the endocrine regulation of pituitary Fsh production and release.

Our experimental models are the zebrafish (Danio rerio), and in collaboration with other research groups (e.g., at the Institute of Marine Research in Bergen, Norway), also economically relevant species, such as the Atlantic salmon (Salmo salar). Points 1 to 3 are mainly approached with the zebrafish model, points 2 (in part) and 4 (mainly) with the Atlantic salmon model.

Current Applied Project

Although the domestication and directional selection for more than 10 generations improved traits such as growth, utilization of feed, and fillet quality of farmed Atlantic salmon, all contributing to the success of commercial salmon farming, the further development of the salmon aquaculture industry is hampered by two reproduction-related problems:

  1. genetic introgression: the mixing of more uniform gene pools of escapees from aquaculture facilities with the diverse gene pools of wild salmon populations;
  2. precocious male puberty: puberty-associated hormonal changes in male salmon generate animal welfare problems and inflict economic damage. Female salmon rarely enter puberty before reaching harvest size due to the much higher metabolic demand of egg compared to sperm production.

To solve the issues associated with genetic introgression and precocious male puberty, we aim to generate infertile salmon for aquaculture.

Our first strategy aims to specifically remove those somatic cells that are required for germ cell survival and development from the gonads, the germ cell-supporting Sertoli and granulosa cells as well as the sex steroid hormone-producing Leydig and theca cells in male and female salmon, respectively. This strategy does not involve genetic modification (GM).

In our second strategy, we will use GM to generate infertile salmon. For each of the possibilities to generate GM salmon, we will generate two different transgenic lines. Salmon from each line can produce offspring when crossed with fish from the same line. However, crossing salmon between the two different lines brings together overlapping cell type-specific promoter activities that allow the expression of protein-based products that eliminate the germ cell-supporting cells and/or germ cells from the gonads.

Because of both the non-GM and GM strategies, germ cells will not survive, leading to infertility in both sexes. In addition, other detrimental effects of precocious male puberty related to sex steroid production, no longer occur in germ cell-free salmon, improving animal welfare conditions and preventing economic damage for fish farmers.