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Review
. 2015 Oct;56(8):637-49.
doi: 10.1002/em.21946. Epub 2015 Mar 28.

Models of germ cell development and their application for toxicity studies

Daniel W Ferreira  1 , Patrick Allard  1
Affiliations
Review

Models of germ cell development and their application for toxicity studies

Daniel W Ferreira et al. Environ Mol Mutagen. 2015 Oct.

Abstract

Germ cells are unique in their ability to transfer genetic information and traits from generation to generation. As such, the proper development of germ cells and the integrity of their genome are paramount to the health of organisms and the survival of species. Germ cells are also exquisitely sensitive to environmental influences although the testing of germ cell toxicity, especially in females, has proven particularly challenging. In this review, we first describe the remarkable odyssey of germ cells in mammals, with an emphasis on the female germline, from their initial specification early during embryogenesis to the generation of mature gametes in adults. We also describe the current methods used in germ cell toxicity testing and their limitations in examining the complex features of mammalian germ cell development. To bypass these challenges, we propose the use of alternative model systems such as Saccharomyces cerevisiae, Drosophila melanogaster, Caenorhabditis elegans, and in vitro germ cell methods that have distinct advantages over traditional toxicity models. We discuss the benefits and limitations of each approach, their application to germ cell toxicity studies, and the need for computational approaches to maximize the usefulness of these models. Together, the inclusion of these alternative germ cell toxicity models will be invaluable for the examination of stages not easily accessible in mammals as well as the large scale, high-throughput investigation of germ cell toxicity.

Keywords: C. elegans; Drosophila; germ cells; germline; meiosis; stem cell; toxicity; yeast.

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Conflict of interest statement

Conflict of Interests

There is no conflict of interest to declare.

Figures

Figure 1
Figure 1. Germ cell development and meiotic differentiation in several model systems
a. Yeast (S. cerevisiae) meiotic differentiation. Within the span of 6 hours, induced diploid cells undergo a last round of pre-meiotic S before initiating meiosis. During Prophase I, synapsis and recombination events occur before homologous chromosome segregation at Anaphase I. b. The C. elegans germline. In the nematode, germline nuclear differentiation is continuous. As the nuclei move along the gonad they concomitantly progress through the various stages of Prophase I starting with Leptotene (Lept) and Zygotene in the most distal region to diakinesis in the most proximal region. Oocytes (orange shading) are fertilized by going through the spermathecal (Sp) to generate embryos. c. Drosophila oogenesis. Germline stem-cells residing in the germarium undergo a division to give rise to another stem cell or a cell that undergoes meiosis. The egg chambers, each containing one oocyte (orange shading) and nurse cells then progress through meiosis as they move forward through the ovariole. By stage 9 of oogenesis, the oocytes have completed Prophase I. d. In vitro generation of mouse PGCs. ES cells in culture are first induced into an epiblast like state by application in the culture media of several factors including FGF, Activin and Knock-out Serum Replacement (KSR). From that stage, PGC-like cells (PGCLC) are induced by application of a combination of BMP4/8b, FGF and KSR.
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