Community Research and Development Information Service - CORDIS



Project ID: 293765
Funded under: FP7-PEOPLE
Country: Netherlands

Chromatin dynamics during spermatogenesis

One in six couples faces infertility problems. To understand the molecular basis of impaired spermatogenesis, European scientists investigated chromatin dynamics.
Chromatin dynamics during spermatogenesis
Half of the cases of infertility are due to impaired male spermatogenesis. In its extreme presentation, this manifests as spermatogenic arrest causing azoospermia. Despite its clinical significance, in most cases the aetiology of spermatogenic arrest remains unknown.

During spermatogenesis, chromatin undergoes rapid and profound changes in composition and function. Proper chromatin architecture and dynamics are central to sperm cell self-renewal, differentiation and meiosis, and safeguard genomic stability. Alterations in the spatiotemporal organisation of chromatin can lead to chromosomal aberrations, initiate spermatogonial apoptosis or trigger spermatogenic arrest.

The primary objective of the EU-funded CHROMATIN IN SSCS (4D analysis of chromatin dynamics during the early stages of spermatogenesis: A journey to the stem of male infertility) project was to investigate spermatogenetic arrest and in particular to delineate the role of chromatin dynamics in the physiology and survival of male reproductive cells.

In the first part of the project, researchers characterised various proteins implicated in the structural maintenance of chromosomes during spermatogenesis. Efforts focused on Smc6, a protein involved in genomic damage responses in yeast and drosophila and expressed at high levels in the testis. Scientists observed that in rodent cells Smc6 prohibited recombination of the repetitive sequences found in pericentromeric heterochromatin regions. This was expected since meiotic recombination should be suppressed in these regions to avoid chromosomal aberrations.

However, in human reproductive cells, scientists saw that Smc6 did not protect against aberrant meiotic recombination. This was attributed to the different architecture and nature of human pericentromeric regions.

Overall, the findings of the CHROMATIN IN SSCS project provided important and unprecedented insight into the molecular mechanism of spermatogenesis. Future studies into the biochemical regulation of Smc6 in genomic damage and chromosomal organisation should fully decipher the functional role of this molecule. Considering the socioeconomic impact of subfertility in western societies, this information brings us a step closer to comprehending the underlying aetiology.

Related information


Chromatin, spermatogenesis, infertility, spermatogenic arrest, CHROMATIN IN SSCS, Smc6
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