Reproductive Biology

Reproductive Biology

RNDr. Kateřina Komrsková, Ph.D.

RNDr. Kateřina Komrsková, Ph.D. — Project head

About us

The Group of Reproductive biology focuses on characterization of processes and molecular factors involved in sperm maturation prior to fertilization (capacitation, acrosome reaction and seminal fluid composition), sperm-egg interaction, specification of anti-sperm antibodies, as well as developing tools for detection of male infertility. 

The group is involved in monitoring of sperm quality in patients with testicular cancer and characterization of reproductive parameters modified by environmental factors with a negative effect on reproduction. This research area includes identification of epigenetic mechanisms participating in gametogenesis connected to gene expression. The goal of the group is to understand in detail localization and behaviour of selected protein prior and during the gamete fusion. The complex approach helps with a detection of pathologies and consequentially lead to prevention, diagnostics and selection of the most appropriate infertility treatment.

Our laboratory has extensive knowledge of assessing male reproductive parameters as markers of fertility disorders. We have been focusing on studying the molecular mechanisms of reproduction and the nature of specific sperm proteins that play a role in sperm maturation, sperm-egg interaction and early embryo development. The area of interest covers monitoring of sperm quality in patients with testicular cancer and diabetes mellitus and sperm antibodies characterization in infertile couples. Many of them are used in Centres of Assisted Reproduction and have been commercialized. Transgenerational epigenetic deregulation of microRNA expression induced by pollutants that influence the key role in germ cell differentiation without changing the DNA has been proven.

Recently, we have been studying in detail characterization of dynamic rearrangement of cytoskeletal proteins and their partner proteins (IZUMO1, CD46, CD9, CD81, CD151 and integrins) involved in sperm-egg fusion. In addition, the acrosin inhibitor expression and crucial ubiquitin proteasomal complex during sperm maturation has been addressed. Epigenetic aberrations (selected histone modifications and DNA methylation) in spermatozoa, testicular tissues and early embryos after exposure to environmental pollutants have been studied and new related project are in progress. All the ongoing research is supported by several prestigious grants. The outcome of this research is being translated into new diagnostic tools for identification of sperm parameters and selection of good and bad sperm to be used in Centres of Assisted Reproduction. This translational research is supported by grants of the Technological Agency of the Czech Republic and the Agency of Ministry of Health. Two European and two Czech patents were submitted.

We have productive collaboration based on the knowledge of the detailed assessment of reproductive parameters, monitoring of transgenerational epigenetic inheritance, characterization of epigenetic aberration and microRNA deregulations, all tailored for specific areas of interest (medical conditions, lifestyle, environmental factors). In addition, we utilize, in collaboration with commercial subjects, our knowledge of hybridoma technology for the production of specific monoclonal antibodies with high affinity, and twelve prototypes for the detection of relevant molecules have been developed. Moreover, we have valuable collaboration based on transgenic mouse lines, property of our laboratory, serving as indispensable tool for in vivo experiments, specifically transgenic C57BL/6Acr3-EGFP mice expressing green protein (EGFP) in sperm acrosome, transgenic C57BL/6Su9DsRed2 mice expressing red fluorescent protein (RFP) in somatic cell mitochondria.

 

MEDIA PRESENTATION

 

ANNOTANTION OF MAJOR RESULTS:

 

1. Characterization of CD46 and β1 integrin dynamics during sperm acrosome reaction.

Proteins CD46 and β1 integrin undergo synchronic dynamic relocation towards the sites of sperm-egg fusion during the acrosome reaction as shown by Super-resolution microscopy. Their interaction was confirmed by proximity ligation assay and their association with actin cytoskeleton was suggested. This protein relocation is suggested to be of importance for successful sperm-egg interaction, adhesion and subsequent gamete fusion and is being targeted as a tool for infertility diagnostics.

 2. CD9 and CD81 Interaction and their Structure Modelling in Sperm Prior to Fertilization.  

The species-specific traits in CD9 and CD81 distribution during sperm maturation were compared between mice and humans. Confocal microscopy and colocalization assay was used to determine a mutual CD9/CD81 localization visualised in detail by super-resolution microscopy, and their interaction was address by co-immunoprecipitation. A mutual position of CD9/CD81 is shown in human spermatozoa in the acrosomal cap, however in mice, CD9 and CD81 occupy a distinct area. During the acrosome reaction in human sperm, only CD9 is relocated, compared to the relocation of both proteins in mice. The structural modelling of CD9 and CD81 homologous and possibly heterologous network formation was used to propose their lateral Cis as well as Trans interactions within the sperm membrane and during sperm-egg membrane fusion.

  • Collaborating institutions: Department of Veterinary Sciences, Faculty of Agrobiology, Food and Natural Resources, University of Life Sciences Prague, Prague 6, 165 00, Czech Republic. Laboratory of Structural Bioinformatics of Proteins, Institute of Biotechnology CAS, v.v.i., BIOCEV, 252 50, Vestec, Czech Republic. Laboratory of Reproductive Physiology, Institute of Animal Biochemistry and Genetics Centre of Biosciences Slovak Academy of Sciences, 845 05 Bratislava, Slovakia. Department of Biochemistry and Department of Zoology, Faculty of Science, Charles University, Prague 2, 128 44, Czech Republic.
  • Contact person: Dr. Katerina Hortova, 604855871, katerina.hortova@ibt.cas.cz
  • Publication: Frolikova M, Manaskova-Postlerova P, Cerny J, Jankovicova J, Simonik O, Pohlova A, Secova P, Antalikova J, Dvorakova-Hortova K. CD9 and CD81 Interaction and their Structure Modelling in Sperm Prior to Fertilization. Int J Mol Sci. 2018 Apr 19;19(4). Pii: E1236. Doi: 10.3390/Ijms19041236.

 

3. Methylation analysis of histone H4K12ac-associated promoters in sperm of healthy donors and subfertile patients.

In men, histone-protamine exchange is incomplete, remaining histones are acetylated which represents an epigenetic mark transmitted from sperm and regulating early embryo gene expression. During mouse fertilization, paternal pronucleus exhibits a strong acetylation on H4K12, while maternal one shows its permanent increase until pronuclei fusion. Aberrant histone acetylation within developmentally important gene promoters in subfertile men but not DNA methylation, may reflect insufficient sperm chromatin compaction affecting the transfer of epigenetic marks to the egg.

  • Collaborating institutions: Section Molecular Andrology, Biomedical Research Center Seltersberg, Justus Liebig University of Giessen, 35392 Giessen, Germany. Department of Zoology, Faculty of Science, Charles University in Prague, 12844 Prague, Czech Republic. Department of Urology, Pediatric Urology and Andrology, Justus Liebieg University of Giessen, 35392 Giessen, Germany. Fertility Center, 35578 Wetzlar, Germany. Fertility Center, 65189 Wiesbaden, Germany.
  • Contact person: Mrs. Kateřina Hortová, 604855871, katerina.hortova@ibt.cas.cz
  • Publication: Vieweg M, Dvorakova-Hortova K, Dudkova B, Waliszewski P, Otte M, Oels B, Hajimohammad A, Turley H, Schorsch M, Schuppe HC, Weidner W, Steger K, Paradowska-Dogan A.: Methylation analysis of histone H4K12ac-associated promoters in sperm of healthy donors and subfertile patients. Clin Epigenetics. 19;7(1):31. 2015 doi: 10.1186/s13148-015-0058-4.

News

Publications

2020

Zigo, M., P. Manaskova-Postlerova, D. Zuidema, K. Kerns, V. Jonakova, L. Tumova, F. Bubenickova and P. Sutovsky (2020). "Porcine model for the study of sperm capacitation, fertilization and male fertility." Cell Tissue Res 380(2): 237-262.

Sreerangaraja Urs, D. B., W. H. Wu, K. Komrskova, P. Postlerova, Y. F. Lin, C. R. Tzeng and S. H. Kao (2020). "Mitochondrial Function in Modulating Human Granulosa Cell Steroidogenesis and Female Fertility." Int J Mol Sci 21(10).

Jankovicova, J., M. Frolikova, V. Palenikova, E. Valaskova, J. Cerny, P. Secova, M. Bartokova, L. Horovska, P. Manaskova-Postlerova, J. Antalikova and K. Komrskova (2020). "Expression and distribution of CD151 as a partner of alpha6 integrin in male germ cells." Scientific Reports 10(1).

Jankovicova, J., Z. Neuerova, P. Secova, M. Bartokova, F. Bubenickova, K. Komrskova, P. Postlerova and J. Antalikova (2020). "Tetraspanins in mammalian reproduction: spermatozoa, oocytes and embryos." Med Microbiol Immunol.

Frolikova, M., T. Otcenaskova, E. Valaskova, P. Postlerova, R. Stopkova, P. Stopka and K. Komrskova (2020). "The Role of Taste Receptor mTAS1R3 in Chemical Communication of Gametes." Int J Mol Sci 21(7).

Bosakova, T., A. Tockstein, N. Sebkova, R. Cabala and K. Komrskova (2020). "Kinetic Model of the Action of 17α-Ethynylestradiol on the Capacitation of Mouse Sperm, Monitored by HPLC-MS/MS." Catalysts 10(1).

2019

Zigo, M., V. Jonakova, P. Manaskova-Postlerova, K. Kerns and P. Sutovsky (2019). "Ubiquitin-proteasome system participates in the de-aggregation of spermadhesin and DQH protein during boar sperm capacitation." Reproduction.

Zigo, M., P. Manaskova-Postlerova, V. Jonakova, K. Kerns and P. Sutovsky (2019). "Compartmentalization of the proteasome-interacting proteins during sperm capacitation." Scientific Reports 9

Simonik, O., J. Sichtar, J. Beran, P. Manaskova-Postlerova, L. Tumova, M. Dolezalova, P. Folkova, L. Stadnik and R. Rajmon (2019). "Low Density Lipoprotein - important player in increasing cryoprotective efficiency of soybean lecithin-based bull semen extenders." Animal Reproduction 16(2): 267-276.

Páleníková, V. and E. Tibenská (2019). "Význam a diagnostika antifosfolipidových protilátok u žien s poruchami reprodukcie." Newslab 10(1): 5.

Jankovicova, J., P. Secova, P. Manaskova-Postlerova, O. Simonik, M. Frolikova, E. Chmelikova, L. Horovska, K. Michalkova, K. Dvorakova-Hortova and J. Antalikova (2019). "Detection of CD9 and CD81 tetraspanins in bovine and porcine oocytes and embryos." Int J Biol Macromol 123: 931-938.

Frolikova, M., E. Valaskova, J. Cerny, A. Lumeau, N. Sebkova, V. Palenikova, N. Sanches-Hernandez, A. Pohlova, P. Manaskova-Postlerova and K. Dvorakova-Hortova (2019). "Addressing the Compartmentalization of Specific Integrin Heterodimers in Mouse Sperm." Int J Mol Sci 20(5).

Ded, L., P. Dostalova, E. Zatecka, A. Dorosh, K. Komrskova and J. Peknicova (2019). "Fluorescent analysis of boar sperm capacitation process in vitro." Reprod Biol Endocrinol 17(1): 109.

Bajzikova, M., J. Kovarova, A. R. Coelho, S. Boukalova, S. Oh, K. Rohlenova, D. Svec, S. Hubackova, B. Endaya, K. Judasova, A. Bezawork-Geleta, K. Kluckova, L. Chatre, R. Zobalova, A. Novakova, K. Vanova, Z. Ezrova, G. J. Maghzal, S. M. Novais, M. Olsinova, L. Krobova, Y. J. An, E. Davidova, Z. Nahacka, M. Sobol, T. Cunha-Oliveira, C. Sandoval-Acuna, H. Strnad, T. C. Zhang, T. Huynh, T. L. Serafim, P. Hozak, V. A. Sardao, W. J. H. Koopman, M. Ricchetti, P. J. Oliveira, F. Kolar, M. Kubista, J. Truksa, K. Dvorakova-Hortova, K. Pacak, R. Gurlich, R. Stocker, Y. Q. Zhou, M. V. Berridge, S. Park, L. F. Dong, J. Rohlena and J. Neuzil (2019). "Reactivation of Dihydroorotate Dehydrogenase-Driven Pyrimidine Biosynthesis Restores Tumor Growth of Respiration-Deficient Cancer Cells." Cell Metabolism 29(2): 399-+.

Baert, Y., K. Dvorakova-Hortova, H. Margaryan and E. Goossens (2019). "Mouse in vitro spermatogenesis on alginate-based 3D bioprinted scaffolds." Biofabrication 11(3).

2018

Zigo, M., K. Kerns, M. Sutovsky and P. Sutovsky (2018). "Modifications of the 26S proteasome during boar sperm capacitation." Cell Tissue Res 372(3): 591-601.

Krejcirova, R., M. Manasova, V. Sommerova, E. Langhamerova, R. Rajmon and P. Manaskova-Postlerova (2018). "G protein-coupled estrogen receptor (GPER) in adult boar testes, epididymis and spermatozoa during epididymal maturation." Int J Biol Macromol 116: 113-119.

Kerns, K., M. Zigo, E. Z. Drobnis, M. Sutovsky and P. Sutovsky (2018). "Zinc ion flux during mammalian sperm capacitation." Nature Communications 9(1): 2061.

Jankovicova, J., K. Michalkova, P. Secova, L. Horovska, P. Manaskova-Postlerova and J. Antalikova (2018). "Evaluation of protein phosphorylation in bull sperm during their maturation in the epididymis." Cell Tissue Res 371(2): 365-373.

Frolikova, M., P. Manaskova-Postlerova, J. Cerny, J. Jankovicova, O. Simonik, A. Pohlova, P. Secova, J. Antalikova and K. Dvorakova-Hortova (2018). "CD9 and CD81 Interactions and Their Structural Modelling in Sperm Prior to Fertilization." Int J Mol Sci 19(4).

Bosakova, T., A. Tockstein, N. Sebkova, O. Simonik, H. Adamusova, J. Albrechtova, T. Albrecht, Z. Bosakova and K. Dvorakova-Hortova (2018). "New Insight into Sperm Capacitation: A Novel Mechanism of 17beta-Estradiol Signalling." Int J Mol Sci 19(12).

2017

Pavlinkova, G., Margaryan, H., Zatecka, E., Valaskova, E., Elzeinova, F., Kubatova, A., Bohuslavova, R., Peknicova, J. Transgenerational inheritance of susceptibility to diabetes-induced male subfertility. Scientific Reports, 7: 4940, 2017. doi: 10.1038/s41598-017-05286-0. ISSN: 2045-2322.

Drab, T., Ren, S., Manaskova-Postlerova, P., Ticha, M., Jonakova, V., Liberda, J. Glycosidases in porcine follicular fluid and their effect in zona pellucida-AWN 1 spermadhesin interaction. Theriogenology, 100: 80-87, 2017. doi: 10.1016/j.theriogenology.2017.06.011. ISSN: 0093-691X.

Dostalova, P., Zatecka, E., Dvorakova-Hortova, K. Of Oestrogens and Sperm: A Review of the Roles of Oestrogens and Oestrogen Receptors in Male Reproduction. International Journal of Molecular Sciences, 15(5): 904, 2017. doi: 10.3390/ijms18050904. ISSN 1661-6596.

Dong, L. F., Kovarova, J., Bajzikova, M., Bezawork-Geleta, A., Svec, D., Endaya, B., Sachaphibulkij, K., Coelho, A. R., Sebkova, N., Ruzickova, A., Tan, A. S., Kluckova, K., Judasova, K., Zamecnikova, K., Rychtarcikova, Z., Gopalan, V., Sobol, M., Yan, B., Pattnaik, B., Bhatraju, N., Truksa, J., Stopka, P., Hozak, P., Lam, A., Sedlacek, R., Oliveira, P. J., Kubista, M., Agrawal, A., Dvorakova-Hortova, K., Rohlena, J., Berridge, M. V., Neuzil, J. Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells. eLife, 6:e22187, 2017. doi: 10.7554/eLife.22187. ISSN 2050-084X.

2016

Bosakova Z, Tockstein A, Adamusova H, Coufal P, Sebkova N, Dvorakova-Hortova K. (2016) Kinetic analysis of decreased sperm fertilizing ability by fluorides and fluoroaluminates: a tool for analyzing the effect of environmental substances on biological events. Eur Biophys J., 45(1):71-9. doi: 10.1007/s00249-015-1078-x.

Maňásková-Postlerová P, Cozlová N, Dorosh A, Šulc M, Guyonnet B, Jonáková V. (2016) Acrosin inhibitor detection along the boar epididymis. Int J Biol Macromol., 82:733-9. doi: 10.1016/j.ijbiomac.2015.10.034.

Capkova J, Kubatova A, Ded L, Tepla O, Peknicova J. (2016) Evaluation of the expression of sperm proteins in normozoospermic and asthenozoospermic men using monoclonal antibodies. Asian J Androl., 18(1):108-13.

Frolikova, M., Sebkova, N., Ded, L., Dvorakova-Hortova, K. Characterization of CD46 and β1 integrin dynamics during sperm acrosome reaction. Scientific Reports, 6: 33714, 2016. doi: 10.1038/srep33714. eISSN 2045-2322.

Jankovicova, J., Frolikova, M., Sebkova, N., Simon, M., Cupperova, P., Lipcseyova, D., Michalkova, K., Horovska, L., Sedlacek, R., Stopka, P., Antalikova, J., Dvorakova-Hortova, K. Characterization of tetraspanin protein CD81 in mouse spermatozoa and bovine gametes. Reproduction, 152: 785-793, 2016. doi: 10.1530/REP-16-0304. ISSN 1470-1626.

2015

Capkova J, Margaryan H, Kubatova A, Novak P, Peknicova J. (2015) Target antigens for Hs-14 monoclonal antibody and their various expression in normozoospermic and asthenozoospermic men. Basic Clin Androl., 25:11. doi: 10.1186/s12610-015-0025-0.

Brieño-Enríquez MA, García-López J, Cárdenas DB, Guibert S, Cleroux E, Děd L, Hourcade Jde D, Pěknicová J, Weber M, Del Mazo J. (2015) Exposure to endocrine disruptor induces transgenerational epigenetic deregulation of microRNAs in primordial germ cells. PLoS One., 10(4):e0124296. doi: 10.1371/journal.pone.0124296.

Zigo M, Dorosh A, Pohlová A, Jonáková V, Šulc M, Maňásková-Postlerová P. (2015) Panel of monoclonal antibodies to sperm surface proteins as a tool for monitoring localization and identification of sperm-zona pellucida receptors. Cell Tissue Res., 359(3):895-908. doi: 10.1007/s00441-014-2072-9

Vieweg M, Dvorakova-Hortova K, Dudkova B, Waliszewski P, Otte M, Oels B, Hajimohammad A, Turley H, Schorsch M, Schuppe HC, Weidner W, Steger K, Paradowska-Dogan A. (2015): Methylation analysis of histone H4K12ac-associated promoters in sperm of healthy donors and subfertile patients. Clin Epigenetics., 19;7(1):31. doi: 10.1186/s13148-015-0058-4

Margaryan H, Dorosh A, Capkova J, Manaskova-Postlerova P, Philimonenko A, Hozak P, Peknicova J.: (2015) Characterization and possible function of glyceraldehyde-3-phosphate dehydrogenase-spermatogenic protein GAPDHS in mammalian sperm. Reprod Biol Endocrinol., 13:15. doi: 10.1186/s12958-015-0008-1.
 

2014

Alavi, S. H. M., Postlerova-Manaskova, P., Hatef, A., Psenicka, M., Peknicova, J., Inaba, K., Ciereszko, A., Linhart, O. Protease in sturgeon sperm and the effects of protease inhibitors on sperm motility and velocity. Fish Physiology and Biochemistry, 40(58): 1393-1398, 2014. doi: 10.1007/s10695-014-9933-8. ISSN 0920-1742.

Dvorakova-Hortova, K., Sidlova, A., Ded, L., Hladovcova, D., Vieweg, M., Weidner, W., Steger, K., Stopka, P., Paradowska-Dogan, A. Toxoplasma gondii decreases the reproductive fitness in mice. PLoS ONE, 9(6): e96770, 2014. doi: 10.1371/journal.pone.0096770. ISSN 1932-6203.

Sebkova, N., Ded, L., Vesela, K., Dvorakova-Hortova, K. Progress of sperm Izumo1 relocation during spontaneous acrosome reaction. Reproduction, 147(2): 231-240, 2014. doi: 10.1530/REP-13-0193. ISSN 1470-1626.

Zatecka, E., Castillo, J., Elzeinova, F., Kubatova, A., Ded, L., Peknicova, J., Oliva, R. The effect of tetrabromobisphenol A on protamine content and DNA integrity in mouse spermatozoa. Andrology, 2(6): 910-917, 2014. doi: 10.1111/j.2047-2927.2014.00257.x. ISSN 2047-2919.

Zatecka, E., Ded, L., Elzeinova, F., Kubatova, A., Dorosh, A., Margaryan, H., Dostalova, P., Korenkova, V., Hoskova, K., Peknicova, J. Effect of zearalenone on reproductive parameters and expression of selected testicular genes in mice. Reproductive toxicology, 45: 20-30, 2014. doi:10.1016/j.reprotox.2014.01.003. ISSN 1873-1708.

2013

Zatecka, E., Ded, L., Elzeinova, F., Kubatova, A., Dorosh, A., Margaryan, H., Dostalova, P., Peknicova, J. Effect of tetrabrombisphenol A on induction of apoptosis in the testes and changes in expression of selected testicular genes in CD1 mice. Reproductive Toxicology, 35: 32-39, 2013. ISSN 0890-6238.

Ded, L., Sebkova, N., Cerna, M., Elzeinova, E., Dostalova, P., Peknicova, J., Dvorakova-Hortova, K. In vivo exposure to 17β-estradiol triggers premature sperm capacitation in cauda epididymis. Reproduction, 145(3): 255-263, 2013. ISSN 1470-1626.

Elzeinova, F., Peknicova, J., Ded, L., Dorosh, A., Kubatova, A., Margaryan, H., Makovicky, P., Rajmon, R. Adverse effect of tetracycline and doxycycline on testicular tissue and sperm parameters in CD1 outbred mice. Experimental and Toxicologic Pathology,65(6): 911-917, 2013. ISSN 0940-2993.

Dorosh, A., Tepla, O., Zatecka, E., Ded, L., Koci, K., Peknicova, J. Expression analysis of MND1/GAJ, SPATA22, GAPDHS and ACR genes in testicular biopsies from non-obstructive azoospermia (NOA) patients. Reproductive Biology and Endocrinology, 11:42, 2013. ISSN 1477-7827.

Zigo, M., Jonakova, V., Sulc, M., Manaskova-Postlerova, P. Characterization of sperm surface protein patterns of ejaculated and capacitated boar sperm, with the detection of ZP binding candidates. International Journal of Biological Macromolecules, 61: 322-328, 2013. ISSN 0141-8130.

2012

Babcova, K., Ulcova-Gallova, Z., Bibkova, K., Micanova, Z., Peknicova J. Semen and serum inhibin B, and sperm quality in infertile men. Andrologia, 21: 3-12, 2012. ISSN 1310-3806.

Capkova, J., Hrncir, T., Kubatova, A., Tlaskalova-Hogenova, H. Lipopolysaccharide treatment suppresses spontaneously developing ankylosing enthesopathy in B10.BR male mice: The potential role of interleukin-10. BMC Musculoskeletal Disorders, 13: 110-118, 2012. ISSN 1471-2474.

Sebkova, N., Cerna, M., Ded, L., Peknicova, J., Dvorakova-Hortova, K. The slower the better: how sperm capacitation and acrosome reaction is modified in the presence of estrogen. Reproduction, 143: 297-307, 2012. ISSN 1470-1626.

Yi, Y. J., Zimmermann, S. W., Manandhar, G., Odhiambo, J. F., Kennedy, C., Jonakova, V., Manaskova-Postlerova, P., Sutovsky, M., Park, Ch. S., Sutovsky, P. Ubiquitin-activating enzyme (UBA1) is required for sperm capacitation, acrosomal exocytosis and sperm-egg coat penetration during porcine fertilization. International Journal of Andrology, 35: 196-210, 2012. ISSN 0105-6263.