Molecular mechanisms of germ cell development

Molecular mechanisms of germ cell development

Ing. Zdeněk Trachtulec, Ph.D.

Ing. Zdeněk Trachtulec, Ph.D. — Project head

The Institute of Molecular Genetics of the Czech Academy of Sciences

About us

The current fertility studies in model mammals move from the effects of single gene to genetic interactions important for human reproductive medicine that occur during spermatogenesis and oogenesis.

The Prdm9 gene (also called Meisetz) is necessary for both male and female meiosis and fertility in the laboratory mouse. The biochemical function of the PRDM9 protein is to methylate histones. The mouse, bovine, and human PRDM9 proteins specify the sites of meiotic recombination. However, PRDM9 is dispensable for fertility in the dog. PRDM9 polymorphisms were revealed in sterile human patients and PRDM9 variation contributes to instability of the human genome. We have identified Prdm9 as the first vertebrate hybrid sterility gene. Different Prdm9 mutations display different stages and degrees of spermatogenetic arrest on various backgrounds, indicating that the resulting phenotype is dependent on genetic interactions of Prdm9.

The aims of the project are: analyses of genes regulating germ cell development in mouse and rat testes and ovaries, interspecific differences important for translation studies; analyses of interactions and  incompatibilities of genes expressed in testes and ovaries; analyses of models of germ cell development defects that are affected by Prdm9, including complete meiotic arrest (azoospermia), limited fertility (reduced sperm count – oligospermia), sperm head malformations (teratozoospermia), and reproductive age defects (time-dependent arrest of germ cell development).

Videoabstract of a current paper (Flachs et al 2014, in Czech with optional English subtitles)




Mihola O, Landa V, Pratto F, Brick K, Kobets T, Kusari F, Gasic S, Smagulova F, Grey C, Flachs P, Gergelits V, Tresnak K, Silhavy J, Mlejnek P, Camerini-Otero RD, Pravenec M, Petukhova GV, Trachtulec Z: Rat PRDM9 shapes recombination landscapes, duration of meiosis, gametogenesis, and age of fertility. BMC Biol 2021 19(1): 86.

Tsyklauri O, Niederlova V, Forsythe E, Prasai A, Drobek A, Kasparek P, Sparks K, Trachtulec Z, Prochazka J, Sedlacek R, Beales P, Huranova M, Stepanek O: Bardet-Biedl Syndrome ciliopathy is linked to altered hematopoiesis and dysregulated self-tolerance. EMBO Rep 2021, e50785.


Kusari F, Mihola O, Schimenti JC, Trachtulec Z: Meiotic epigenetic factor PRDM9 impacts sperm quality of hybrid mice. Reproduction 2020 160(1): 53-64.

Mihola O, Kobets T, Krivankova K, Linhartova E, Gasic S, Schimenti JC, Trachtulec Z: Copy-number variation introduced by long transgenes compromises mouse male fertility independently of pachytene checkpoints. Chromosoma 2020 129(1): 69-82


Mihola O, Pratto F, Brick K, Linhartova E, Kobets T, Flachs P, Baker CL,
Sedlacek R, Paigen K, Petkov PM, Camerini-Otero RD, Trachtulec Z:
Histone methyltransferase PRDM9 is not essential for meiosis in male
mice. Genome Research 2019 29:1078-1086


Mihola O, Trachtulec Z: A Mutation of the Prdm9 Mouse Hybrid Sterility Gene Carried by a Transgene. Folia Biol (Praha) 2017 63(1): 27-30.


Balcova M, Faltusova B, Gergelits V, Bhattacharyya T, Mihola O, Trachtulec Z, Knopf C, Fotopulosova V, Chvatalova I, Gregorova S, Forejt J: Hybrid Sterility Locus on Chromosome X Controls Meiotic Recombination Rate in Mouse. PLoS Genet 2016 12(4): e1005906.


Baker CL, Petkova P, Walker M, Flachs P, Mihola O, Trachtulec Z, Petkov PM, Paigen K: Multimer Formation Explains Allelic Suppression of PRDM9 Recombination Hotspots. PLoS Genet 2015 11(9): e1005512.


Flachs P, Bhattacharyya T, Mihola O, Piálek J, Forejt J, Trachtulec Z: Prdm9 incompatibility controls oligospermia and delayed fertility but no selfish transmission in mouse intersubspecific hybrids. PLoS One 2014 9(4): e95806.


Bhattacharyya T, Gregorova S, Mihola O, Anger M, Sebestova J, Denny P, Simecek P, Forejt J.: Mechanistic basis of infertility of mouse intersubspecific hybrids. Proc Natl Acad Sci U S A. 2013 110(6):E468-77.


Flachs P, Mihola O, Simecek P, Gregorova S, Schimenti JC, Matsui Y, Baudat F, de Massy B, Pialek J, Forejt J, Trachtulec Z: Interallelic and Intergenic Incompatibilities of the Prdm9 (Hst1) Gene in Mouse Hybrid Sterility. PLoS Genetics 2012 8(11): e1003044.

Forejt J, Pialek J, Trachtulec Z: Hybrid male sterility genes in the mouse subspecific crosses. Evolution of the House Mouse. In: Macholan M, Ed. Macholan M, at all, Cambridge University Press 2012, 482-503.


Mihola O, Trachtulec Z, Vlcek C, Schimenti JC, Forejt J: A mouse speciation gene encodes a meiotic histone H3 methyltransferase. Science 2009 323(5912): 373-5.


Gregorová S, Divina P, Storchova R, Trachtulec Z, Fotopulosova V, Svenson KL, Donahue LR, Paigen B, Forejt J: Mouse consomic strains: exploiting genetic divergence between Mus m. musculus and Mus m. domesticus subspecies. Genome Res 2008 18(3): 509-15.

Trachtulec Z, Vlcek C, Mihola O, Gregorova S, Fotopulosova V, Forejt J: Fine haplotype structure of a chromosome 17 region in the laboratory and wild mouse. Genetics 2008 178(3): 1777-84.


Mihola O, Forejt J, Trachtulec Z: Conserved alternative and antisense transcripts at the programmed cell death 2 locus. BMC Genomics 2007 8: 20.


Trachtulec T, Mihola O, Vlček Č, Himmelbauer H, Pačes V, Forejt J: Positional cloning of the Hybrid sterility 1 gene: fine genetic mapping and evaluation of two candidate genes. Biological Journal of the Linnean Society 2005 84(3): 637-641.

Vyskocilova M, Trachtulec Z, Forejt J, Pialek J: Does geography matter in hybrid sterility in house mice? Biological Journal of the Lennean Society 2005 84(3): 663-674.