previously: X 2021 – V 2025 Research Team of Sperm Genetics
Head: dr hab. n. med. i n. o zdr. Marta Olszewska
marta.olszewska@igcz.poznan.pl
tel.: +48 668 08 3132
pokój B9
www.nieplodnosc-meska.pl
Group Members
Now:
mgr Zuzanna Graczyk – PhD Student
mgr Aleksandra Leśniewska – Biologist
our Students and Trainees:
Amelia Danielewska
Agata Makarska-Guzikowska
Klaudia Kasprzak
Patrycja Mazurek
Aleksander Jurkiewicz
Past Members or Graduated Students:
Jagoda Kostyk, MSc Eng
Zuzanna Myślicka, MSc Eng.
Julia Pospieszna, MSc Eng.
Martyna Żurek, MSc Eng.
Aleksandra Zasina, MSc Eng.
The infertility is a social disease concerning about 10-18% of couples. It is estimated that male factor determines 30-40% of all couples’ infertility cases. It became clear that numerous factors, that can be reciprocally related between each other and which disturbances are being observed in males with reproductive failures, pays attention to the complexity of the problem. Beside of a variety of known molecular and environmental factors, also the light should be shed on so-called epigenetic factors, which are non-genetic modifications of the genome. Among them the methylation of sperm DNA and methylation/acetylation of the sperm histones seems to play crucial role in proper spermatogenesis and embryo development. Another non-genetic factor is the positioning of chromosomes within sperm nucleus, what means the defined localization of particular chromosomes. Spermatozoa characterizes unique nuclear packaging of the chromatin, thus the chromosomes’ positions are also specific. It is known that in men with various disturbances of fertility the nuclear organization is changed. There are also evidences that epigenetic changes are prone both to: genetics, as well as for environmental factors. What is interesting, relative interaction between them may work as a cause or a reason of disturbances in male fertility.
The research tasks of the Group are based on a comprehensive experimental approach to spermatozoa of males with oligozoospermia, as well as of chromosomal aberrations carriers, taking into account the characteristics of both: the genetic and epigenetic content of the sperm cell important for the course of spermatogenesis. Simultaneous evaluation of all the above-mentioned parameters may be a stimulus to develop new tests assessing both the structural and regulatory layer of the sperm genetic material.
Currently, the Group implements the research tasks following epigenetic and cytogenetic aspects of human spermatozoa from males with reproductive failures following, as well well aims within the Department of Reproductive Biology and Stem Cells, where we also focus on searching for genetic and genomic variants in men with reduced semen parameters in genome and methylome screening studies and in mouse models of infertility.
OUR PROJECTS:
- ‘Cytogenetic and molecular analyses of positioning of human sperm chromosomes, including: sperm chromatin integrity, epigenetic marks, karyotyping and sperm fractioning’ SONATA BIS National Science Centre, no. 2020/38/E/NZ2/00134 (2021-2026)
The main purpose of the Project is to determine how the positions of the chromosomes within human sperm nucleus may be altered depending on: the state of fertility, karyotype, chromatin integrity status, epigenetic variations within DNA or histones, and between members of the same family, incl. various fractions of sperm cells. The novelty of the Project is that all analyses will be done sequentially on the same individual sperm cells, what means that the positioning of the chromosomes will be prepared in particular single spermatozoa, cell by cell, with known and documented: genotype, chromatin integrity state, and epigenetic marks level/change. Tests will be performed in males with normal karyotype (control, fertile vs. infertile from the same family, i.e. brothers), and with chromosomal abnormalities but phenotypically normal (i.e. carriers of chromosomal translocations). All tests will be performed on various sperm fractions: sperm with good motility, mature chromatin, and defined fertilization potential.
Carriership of balanced chromosomal rearrangements (CR) can be called: a ‘hidden biological bomb’, because aberrations frequently do not affect carriers’ phenotype, contrary to its negative influence on spermatogenesis. CR carriers may be at risk for abnormal pregnancy and/or offspring with developmental disabilities, because of the production of genetically unbalanced gametes during improper meiotic segregation. It is important, especially in the context of IVF techniques, where only visual evaluation of sperm motility and morphology is performed when selecting sperm cell for IVF procedure.
- Analysis of DNA methylation pattern in spermatozoa of infertile men with oligozoospermia’ SONATA National Science Centre, no. 2015/17/D/NZ5/03442 (2016-2020)
The purpose of the Project is to delineate methylation pattern for selected genes in DNA from spermatozoa of infertile men with diagnosed oligozoospermia (low sperm count in ejaculate). It is assumed that spermatozoa of oligozoospermic males may have changed methylation patterns of genes that are crucial for spermatogenesis, what may influence their fertility status. Moreover, in spermatozoa of oligozoospermic males also other genomic elements may be disrupted, including: sperm chromatin integrity (deprotamination and DNA fragmentation) and higher sperm aneuploidy level. The purpose of the Project is carrying out via complex characterization of spermatozoa from infertile males with oligozoospermia, including: (i) methylation pattern analysis of sperm DNA in promotor sequences for selected genes (gene panel and/or whole methylome sequencing), (ii) global methylation analysis of sperm DNA, followed by analysis of methylation and acetylation of selected histones’ residues, followed by their immunolocalization within human sperm nuclei, (iii) sperm chromatin integrity analysis, (iv) analysis of aneuploidy level for selected chromosomes in spermatozoa.
- „Searching for the causes of male infertility – high-throughput genomic study of the Polish population” Ministry of Science and Higher Education, program: Science for society II, nr NdS-II/SP/0288/2024/01 (2024-2027)
The aim of the project is to create a database of genomic variants important for infertile men from the Polish population. It will be achieved by compiling molecular biology methods, including the latest methods of high-throughput genome research: whole genome sequencing (WGS), whole genome methylome sequencing (WGMS), as well as verification of results at the protein level. The research will be conducted on a group of 100 infertile men with reduced semen parameters and normal karyotype. The proposed research postulates a prospective method of diagnosing patients with reproductive failures, which in terms of “for the patient” will allow for receiving a personalized diagnosis with an estimate of the risk of reproductive failures, and from the “scientific” side will contribute to the identification of new genes responsible for the so-called male factor.
Funding agency: Ministry of Science and Higher Education
Programm: Science for Society II
No.: NdS-II/SP/0288/2024/01
Schedule: 13.06.2024 – 13.06.2027
Financial support: 1 000 000 PLN
Principal Investigator: dr hab. Marta Olszewska
Main Investigator: dr Agnieszka Malcher
Website: http://www.nieplodnosc-meska.pl
- „Spatial visual transcriptomics approach of male and female gonad – validation of the role of candidate infertility genes in ‘knockout’ mice models” OPUS National Science Centre, 2024/53/B/NZ5/02183 (2025-2029)
In vivo studies using a “knockout” mouse models will allow us to learn about the effect of disorders resulting from reduced expression of the studied genes or its complete lack on the course of the gametogenesis process. The results obtained on the basis of studies of the structure and expression of selected genes will allow us to answer the question of the occurrence of differences in fertility depending on sex, as well as the universal effect of some genes on the production of reproductive cells in both sexes. Studies conducted on females will allow us to check the role of the studied genes in oogenesis and the functioning of the ovary, which will complement studies of spermatogenesis disorders conducted complementarily on males. The entire study will be conducted using the spatial transcriptomics technique (visium spatial transcriptomics 10X Genomics) at the level of single cells, which will allow us to learn about the detailed effect of the studied mutation on a number of other genes in the gonad.