Epigenetic information contained in male germ cell chromatin-associated proteins and its potential impact on the reproductive function
[eng] Contrasting the traditional idea of the male gamete being a simple carrier of the paternal DNA, evidence in the last decades revealed that the sperm cell provides the embryo with different layers of epigenetic information, which is not limited to DNA methylation and non-coding RNAs but also in...
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| Formato: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Recursos: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/208863 |
| Acesso em linha: | https://hdl.handle.net/2445/208863 http://hdl.handle.net/10803/690344 |
| Access Level: | acceso abierto |
| Palavra-chave: | Epigenètica Cromatina Espermatozoides Epigenetics Chromatin Spermatozoa |
| Resumo: | [eng] Contrasting the traditional idea of the male gamete being a simple carrier of the paternal DNA, evidence in the last decades revealed that the sperm cell provides the embryo with different layers of epigenetic information, which is not limited to DNA methylation and non-coding RNAs but also involves the protein fraction of the sperm chromatin. Posttranslational modifications (PTMs) of chromatin-associated proteins, together with a complex population of proteins with gene regulatory roles, would also have an impact in fertilization and pre-implantation embryo development. Furthermore, the sperm chromatin, understood as the association between DNA and two different types of proteins, histones and protamines, both bearing PTMs, and resulting in two distinct genome compaction states, arises as a new concept of epigenetic mark that is exclusive for the male gamete. The relevance and peculiarities of sperm chromatin have attracted interest over the years, and many efforts have been made to disentangle it, not only in mature sperm but also during spermatid differentiation. However, male germ cells’ chromatin is as attractive as challenging, and its study requires the adaptation of conventional techniques or application of new ones. Despite that, many important factors have been related with the regulation and formation of the sperm chromatin, as well as with the correct transmission of parental epigenetic information to the zygote. Thus, protamines, histones, and their PTMs, both during male gamete development and once matured, as well as the peculiarly compacted chromatin structure of mature sperm, emerge as interesting features to be further studied to increase the current knowledge on the epigenetic content of the protein fraction of sperm chromatin and its potential involvement in cases of unexplained male infertility. The objectives of this doctoral thesis are: 1) To explore histone PTMs involved in the process of nucleo-histone to nucleo-protamine transition and their epigenetic potential, 2) To increase the knowledge on protamine proteoforms, with a special focus on protamine phosphorylation, and 3) To apply innovative approaches to the study of the sperm chromatin and chromatin compaction defects through the use of small X-ray scattering (SAXS) with synchrotron light for the nanoscale characterization of the sperm nucleus. Besides, objective 1 is subdivided into 1a) to describe alterations of a global histone H4 acetylation pattern during the spermatogenesis in different testicular affections, and 1b) to characterize specific novel acylations during spermatogenesis and in mature sperm (H4K5 acetylation and butyrylation) and their relationship with sperm quality. In turn, objective 2 comprises 2a) to define the normal profile of protamine PTMs through top-down proteomics and to identify alterations in the protamine proteoforms related with unexplained infertility and 2b) to explore the protein interactive networks of proteins modulating protamine phosphorylation. |
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