The effects of environmental pollutants on meiotic recombination

master's thesis

• Title (croatian): Utjecaj okolišnih zagađivača na mejotičku rekombinaciju
• Author: Lucija Šimunović
• Mentor: Igor Stuparević (mentor)
• Granter: University of Zagreb; Faculty of Food Technology and Biotechnology; (Department of Chemistry and Biochemistry); (Laboratory for Biochemistry); Zagreb
• Defense date and country: 2024-07-03, Croatia
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Biotechnology

Abstract

A great amount of research is focused on understanding the direct effects of toxicants in vivo, but there is not enough knowledge about their impact on fertility and future generations. The oocytes or sperm are the only cells transferred to the offspring, and it is important to know if environmental pollutants induce any inheritable changes. In most eukaryotes, the pairing and recombination between homologous chromosomes is a crucial part of meiosis progression, therefore the events of meiosis are tightly coordinated to ensure the proper execution of these events. Because this process is so complex and strictly regulated, there are a great number of events that could influence the appropriate continuity of meiosis. The ultimate goal is to produce haploid cells necessary for the process of fertilization and restoration of euploidy. The introduction of DNA double-strand brakes (DSBs) is a crucial step of meiotic recombination because a subset of meiotic DSBs are resolved as crossovers which are essential for the formation of chiasmata; a connection between homologs that will ensure proper segregation by the end of anaphase I. Crossover positioning depends on various factors, especially epigenetic modifications such as DNA methylation, histone modifications, and non-coding RNAs. If there is a disturbance in the meiosis, the homologs will not segregate properly, and the outcome can be random segregation and aneuploidy and finally, it could lead to the reduction in the gamete production. In this research, we focused on intergenerational effects in the mice exposed to environmental pollutants. We analyzed gene expression by performing reverse transcription quantitative polymerase chain reaction (RT-qPCR), the epigenetic landscape by chromatin immunoprecipitation (ChIP) and methylated DNA immunoprecipitation (MeDIP), and meiosis progression by immunostaining. These methods were done using the samples of the treated mice (F0) as well as their untreated progeny (F1). The collected data suggests that the exposure of male mice to common environmental pollutants including Cadmium, Ochratoxin A, and Perfluorooctanoic acid changes the expression level of DNA repair genes, perturbs the proper course of meiosis and induces many significant epigenetic changes in the testis which are preserved in sperm. The observed changes in DNA methylation and histone modifications at recombination hotspots as well as changes in the expression of DNA repair genes suggest that these pollutants have intergenerational effects and potentially impair the reproductive health of male progeny.

• Keywords: meiosis; epigenetics; testis; environmental pollutants; intergenerational inheritance
• Language: english
• URN:NBN: urn:nbn:hr:159:887291
• Study programme: Title: Molecular Biotechnology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka molekularne biotehnologije (magistar/magistra inženjer/inženjerka molekularne biotehnologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2024-11-19 13:56:40