Reproductive Disorders Genetics Laboratory
The Reproductive Disorders Genetics Laboratory (RDGL) was founded at Moscow Genetic Research Centre in 1992. Prof. Lyubov Fedorovna Kurilo, Doctor of biological science, was its founder and the first leader.
is the study of causes and mechanisms of hereditary and genetically determined diseases development in female and male reproductive system, reproductive and human fertility disorders. To provide a successful differential diagnosis of these diseases, the Laboratory uses various methods to identify the abnormality at all following levels: molecular (DNA-diagnostics, biochemical screening), subcellular (using electron microscopy, cytogenetic tests), cellular and organ (optical cellular and histological specimen), organismic (methods of clinical examination).
The Laboratory Activity and Research
The Laboratory team carries out the research, scientific and diagnostic, scientific counseling and educational work in the following priority areas:
- Study of the structure, etiology and pathogenesis of genetic diseases of the reproductive system.
- Cytogenetics, molecular genetics and cytopathology of spermatogenesis and oogenesis.
- Comprehensive medical and genetic examination of patients with sex-linked and reproductive function disorders (infertility, miscarriage).
- Elaboration of protocols for the comprehensive examination of patients with various forms of reproductive system disorders.
- Patterns of gametogenesis and gonadogenesis of mammals and humans, genetic regulation of the formation and development of human organs in male and female reproductive system.
- Analysis of the damaging effects of gametotoxic factors. Development of methods for testing the gameto-and gonadotoxic effect of the damaging factor.
- Genetic and biomedical issues of mammals and humans reproduction.
- Moral ethical and legal issues in genetics, human reproduction and other biomedical technologies.
Main Research Areas and Achievements of the Laboratory
I. Patterns of gametogenesis and gonadogenesis of mammals and humans
- Fundamental issues of chronology, dynamics and patterns of development of male and female gonads and germ cells of humans and several species of mammals (cows, green monkeys, pigs, rats, mice) have been studied.
- Original schemes of oogenesis and spermatogenesis have been created (Kurilo L.F., 1983, 1989–85, 1989, 1996, which are included in relevant textbooks and monographs)
- They were first to prove with the use of quantitative method, that the formation of primordial follicles (for example, in humans, cows, mice, and rats) occurred after the completion of conjugation (in zygotene) and crossing-over (in pachytene): around oocytes at the stage of diplonema meiosis prophase 1 (Kurilo, 1980 1985; Kurilo, 1981; Teplyakova, Kurilo et al., 1984).
- First in the world a quantitative method traced the development of stages: the preleptotene condensation and de-condensation of chromosomes in oocytes in humans, cows, mice and rats, and in male germ cells of the embryo and the human fetus; condensation of chromosomes and their localization around the nucleolus (karyosphere stage) in oocytes before diakinesis from maturing follicles in humans, cows, green monkeys (Kurilo, 1981; 1982, 1984, 1985; Kurilo et al. 1983; 1986).
- Bragina E.E., Doctor of biological science, developed a method of sperm electron microscopic analysis (SEMA). The introduction of SEMA into the practice of andrological and medical-genetic examination of patients with reproduction disorders made it possible to obtain significantly new data on the nature of male fertility disorder and idiopathic infertility. SEMA made it possible to detect abnormalities in spermatozoa that were not previously available with light-optical microscopy: it was possible to establish the nature of microstructural anomalies of gametes, in particular, such forms of teratozoospermia as anomalies of the centrioles and chromatin structure, to detect intracellular viral infection.
II. Development of a testing system for gametotoxic effect, schemes and quantitative criteria for its evaluation (for oogenesis and spermatogenesis)
Kurilo L.F. developed a new direction in gameology, namely, the quantitative testing of gametes state according to the stages of their development (gametogenesis). The author's methods, systems and criteria for quantifying gamete-and gonadotoxic effects (physical, chemical and biological factors) on male and female sex cells and sex glands of humans and animals have been developed for this area of research. These methods are used in diagnosing the causes of infertility and gametopathies, in testing the damaging gonad and gamete factor, in analyzing the effectiveness of gametogenesis disorders treatment, as well as in preventing these conditions. They showed the damage of oogenesis and spermatogenesis in the offspring of the first generation (F1) of mice and rats after administration of a number of toxic compounds to pregnant females (ThioTEPA, alcohol, nicotine, oxytetracycline), and discovered the prolonged effect of the examined compounds on the oogenesis and spermatogenesis F1. Patents were obtained for three of the developed methods: 1) Kurilo L.F. "Method of cytological diagnosis of spermatogenesis disorders", patent for invention No. 2328736 of 1/2-2007; 2) Kurilo L.F. "Method for ovarian generative potency diagnosis ", patent for invention No. 2367949 of 03/4-2008; 3) Korolev Yu.N., Kurilo L.F., Nikulina L.A., Panova L.N., Geniatulina M.S., Shileiko L.V. "Method of secondary prevention of spermatogenesis disorders when exposed to radiation" patent for invention No. 2169571.
III. Analysis of the structure, causes and developmental mechanisms of the human reproductive system hereditary pathology
- Determination of frequency and types of chromosomal aberrations (CA) of sex chromosomes and autosomes (in peripheral blood lymphocytes and germ cells) for infertility in men and women, for disorders of sexual development in children of both genders.
- Identification of frequency and types of the long arm of Y-chromosome microdeletions (at Yq11.2 locus (AZF, Azoospermia factor) - azoospermia factor) in Russian men with infertility associated with various forms of impaired spermatogenesis and pathozoospermia (in particular, with developmental non-obstructive forms of azoospermia and severe oligozoospermia).
- Analysis of mutations and polymorphisms of some genes that control the development and function of the reproductive system (AR/HUMARA, CFTR) in patients with various forms of reproductive system disorders, and in fertile men.
- Analysis of genetic causes for impaired differentiation of the reproductive system in humans (at different levels of gender formation). Research on the relationship between genetic changes (chromosomal abnormalities, microstructural chromosome rearrangements, gene mutations and polymorphisms) associated with reproductive disorders and the phenotype in syndromic and non-syndromic abnormality of the reproductive system (cystic fibrosis, CBAVD syndrome, Klinefelter syndrome, Shereshevsky-Turner syndrome, de la Chapelle syndrome/46-XX-male, ovotestichulyarnaya form of sex development disorder, various forms of gonadal dysgenesis, gonosomic mosaicism and other genetically determined reproductive system disorders).
- Examination of nature and patterns of sex chromosomes (gonosome) various mutations and gonosomic mosaicism in various cell lines, genotyphenotypic relationship of sex development anomalies and reproductive system development, gametogenesis and fertility disorders in patients with some numerical, structural and microstructural aberrations of their sex chromosomes, their impacts on reproduction and human fertility.
- Development of new methods of molecular genetic diagnostics (chromosomal abnormalities and gene mutations) of disorders of reproductive system development and function in humans (jointly with DNA-diagnostics Lab., FSBI RCMG, Laboratory head is Prof. Polyakov A.V., Doctor of biological science).
- Study of meiosis process and formation of a synaptonemal complex in patients with impaired spermatogenesis and male infertility, including those associated with genetic causes (chromosomal abnormalities, microdeletions of the Y chromosome). Elaboration of approaches to identification of human meiotic mutations (jointly with the Cytogenetics Laboratory of the Research Institute of General Genetics named after N.I. Vavilov of RAS, Laboratory head is Prof. Kolomiets O.L., Dr. of biological science)
- Analysis of the impact of chromosomal aberrations (CA) in ejaculate germ cells on gametogenesis and fertility. Estimation of chromosomes nondisjunction frequency in gametes of karyotype constitutive anomalies carriers (balanced translocations, inversions and supernumerary marker chromosomes) with different fertility status (jointly with the Cytogenetics Laboratory of the FSBI RCMG, Laboratory head is Shilova N.V. Dr. of medical science).
- Identification of specific anomalies of various gamete ultrastructures (chromatin and DNA of sperm cells, acrosomes, flagellum, fibrous layer, mitochondria, etc.) and somatic cells of male and female reproductive systems in certain forms of male and female infertility. Among them are the absence of dynein arms or central duplet of microtubules axonemes of spermatozoa in primary ciliary dyskinesia and Kartagener syndrome; chromatin condensation disorder in "immature" chromatin syndrome, globuzoospermia (sperm cell acrosome) and sperm fibrosis dysplasia syndrome, Sertoli cells abnormalities in severe forms of pathozoospermia, and endometrial transformation abnormalities in embryonic implantation disorders.
- Analysis of genital infections (viral, bacterial, protozoal) impact on gametogenesis and reproductive function (including male and female infertility and miscarriage). We were the first in the world to identify intra-gamete viral infection in male germ cells.
- Establishing of a database (electronic resources) on genetically determined diseases of the reproductive system.
IV. Study of moral, ethical, and legal issues in genetics and human reproduction, and the use of biomedical technologies.
- The degree of awareness of the population, specialists in medical fertility science and patients (with childbearing problems) in the ethical and legal issues of human reproduction (by means of a survey).
- Ethical and legal issues in the use of reproductive and other biomedical technologies.
- “Human embryo status” – international and domestic (Russian) legislation.
- In 1997-2003, Kurilo L.F. has been an expert of the working group on protection of human embryos and fetuses (CDBI-co-GT3) under the Council of Europe's Steering Committee on Bioethics. A Report has been published (the title is given in the References).
- Kurilo L.F. is one of co-authors of the Federal Law on Temporary Prohibition of Human Cloning (2002). Since 2011, this law has been extended indefinitely.
- Kurilo L.F. Oogenesis in antenatal development in man. Hum Genet. 1981;57(1):86-92.
- Kurilo L.F. Female and male gametes. Chapter 4 of the Book: Intrauterine human development. Ed. Milovanov A.P., Saveliev S.V. Handbook for doctors. Moscow, MDV, 2006, p. 45-52.
- Chernykh V.B., Chukhrova A.L., Beskorovainaya T.S., Grishina E.M., Sorokina T.M., Shileyko L.V., Gogolevsky P.A., Kalugina A.S., Morina G.V., Togobetsky A.S., Tanevsky V.E., Zdanovsky V.M., Gogolevskaya I.K., Kramerov D.A., Polyakov A.V., Kurilo L.F. Types of Y chromosome deletions and their frequency in males with infertility. Genetics. - 2006 - V.42. №8. - p. 1130-1136. [Chernykh V.B., Stepanova A.A., Beskorovainaya T.S., Sorokina T.M., Shileiko L.V., Kurilo L.F., Polyakov A.V. The frequency and spectrum of mutations and the IVS8-T polymorphism of CFTR gene in Russian infertile men. Russian Journal of Genetics. 2010; 46(6):844-852.]
- Kurilo L. F., Adamyan L.V. Urogenital system. Chapter 20. Book: Intrauterine human development. Ed. Milovanov A.P., Saveliev S.V. Handbook for doctors. Moscow, MDV, 2006, p. 324-334.
- Chernykh V.B. Macro and microstructural rearrangements of Y chromosome. Medical Genetics. - 2007 - V. 6, №10 (64). - p. 45-52.
- Gribencha S.V., Bragina E.E., Abdumalikov R.A., Bocharova E.N., Kurilo L.F. Detection of type 2 herpes simplex virus in cells of spermatogenic epithelium in infected testes of guinea pigs. Bull Exp Biol Med. 2007;144(1):73-76.
- Chernykh V.B., Chukhrova A.L., Wasserman N.N., IlIna E.V., Karmanov M.E., Fedotov V.P. Kurilo L.F., Polyakov A.V. Molecular analysis of Y chromosome in XX sex-reversed patients. Russian Journal of Genetics. 2008; 44 (2): 197-201.]
- Chernykh V.B., Vyatkina S.V., Antonenko V.G., Shilova N.V., Zolotukhina T.V., Kurilo L.F., Chukhrova A.L., Polyakov A.V. Unique mosaic X/Y translocation/insertion in infant 45, X male. Am J Med Genet A. 2008 15;146A(24):3195-3197.
- Chernykh V.B., Kurilo L.F., Shilova N.V., Zolotukhina T.V., Ryzhkova O.P., Bliznetz E.A., Polyakov A.V. Hidden X chromosomal mosaicism in a 46,XX male. Sex Dev. 2009;3(4):183-187.
- Chernykh V.B. AZF deletions are a common genetic cause of male infertility: current state of research. Reproduction issues. - 2009 - V. 15; №1. - p. 10-15.
- Chernykh V.B., Stepanova A.A., Beskorovainaya T.S., Sorokina T.M., Shileiko L.V., Kurilo L.F., Polyakov A.V. The frequency and spectrum of mutations and the IVS8-T polymorphism of the CFTR gene in Russian infertile men. Russian Journal of Genetics. 2010; 46(6):844-852.
- Kurilo L.F., Sorokina T.M., Chernykh V.B., Bragina E.E., Gordeeva E.G., Shileyko L.V., Myasnikov D.A. Goncharova N.N., Marchenko L.A., Zhakhur N.A., Sonova M.M., Kolomiets O.L. The structure of genetically determined diseases of the reproductive organs in humans. Andrology and Genital Surgery. - 2011 - № 3 - p. 17-26
- Raygorodskaya N.Y., Chernykh V.B., Morozov D.A., Olutoye O.O., Bolotova N.V., Averyanov A.P., Maslyakova G.N., Shilova N.V., Zolotukhina T.V. A 3-year-old boy with ovotestes: gender reassignment and surgical management. Journal of Pediatric Endocrinology and Metabolism. – 2011 –V. 24 (7-8). – P. 587–589.
- Naumenko V.A., Tyulenev Y.A., Yakovenko S.A., Kurilo L.F., Shileyko L.V., Segal A.S., Zavalishina L.E., Klimova R.R., Tsibizov A.S., Alkhovskii S.V., Kushch A.A. Detection of human cytomegalovirus in motile spermatozoa and spermatogenic cells in testis organotypic culture. Herpesviridae. 2011 28;2(1):7.
- Gordeeva E.G., Shileiko L.V., Pankratova O.S., Kurilo L.F. Aneuploidy frequency in sperm of fertile men. Russian Journal of Genetics. 2011; 47(6):828-835.
- Kurilo L.F., Zhuchenko L.A., Kozlova C.I. Periconceptional prevention of congenital and hereditary pathology. Pp. 833-853. Chapter 31 in the book: National Guide "Hereditary Diseases", Ch. Ed .: Bochkov N.P., Ginter E.K., Puzyrev V.P., M .: "GEOTAR-Media", 2012, p. 936
- Kurilo L. Regularities of ovariogenesis and oogenesis of mammals. Lambert Acad. Publ., 2012, p.280
- Kurilo L.F., Andreeva, M.V., Kolomiets O.V., Sorokina T.M., Chernykh V.B., Shileiko L.V., Khayat S.Sh. Demikova N.S., Kozlova S.I. Genetic syndromes with developmental disorders of the reproductive system organs. Andrology and genital surgery. 2013; 14 (4): 17-27.
- Volkova O.V., Balashov V.P., Bogolepova I.N., Ermolin I.L., Erofeeva L.M., Kapitonova M.Yu., Kruglyakov P.P., Kurilo L.F., Pavlov A.V., Rudinskaya L.S., Saveliev S.V., Soloviev G.S., Stepanova I.P., Shvalev V.N., Shevlyuk N.N., Yamshchikov N.V., Yanin V. .L. International terms on human embryology with the Russian equivalents official list. Russian embryological nomenclature commission. Ed .: Kolesnikov A.L., Shevlyuk N.N., Erofeev L.M.. M .: Publishing Group "GEOTAR-Media", 2014, p. 422.
- Kurilo L.F. Reproductive system abnormalities due to gene mutations. Clinical and experimental morphology, 2014, № 2, p. 58-65.
- Chernykh V.B., Rudneva S.A., Sorokina T.M., Shileiko L.V., Kurilo L.F., Ryzhkova O.P., Chukhrova A.L., Polyakov A.V. Characteristics of spermatogenesis condition in men with infertility, having different types of deletions in the AZFc-region. Andrology and genital surgery. 2014; 15 (2): 48-57.
- Kurilo L.F. Chromosomal diseases of the reproductive system. Clinical and experimental morphology, 2015, No. 3, P. 48-59.
- Chernykh V.B., Rudneva S.A., Sorokina T.M., Shileiko L.V., Ostroumova T.V., Ermolaeva S.A., Kurilo L.F., Ryzhkova O.P., Bliznets E.A., Chukhrova A.L., Polyakov A.V. Impact of CAG-polymorphism of androgen receptor (AR) gene on spermatogenesis in men with infertility. Andrology and genital surgery. 2015; 16 (4): 55-61.
- Kurilo L.F., Khayat S.Sh. Testing possibilities of mitosis and meiosis processes in female and male germ cells. Andrology and genital surgery, 2016, №4, p. 28-37.
- Nemtsova M.V., Ivkin E.V., Simonova O.A., Rudenko V.V., Chernykh V.B., Mikhaylenko D.S., Loran O.B. Polymorphisms of KITLG, SPRY4, and BAK1 genes in patients with testicular germ cell tumors and patients with infertility associated with AZFc deletion of Y chromosome. Mol Biol (Mosk). 2016 Nov-Dec;50(6):960-967.
- Elkina Y.L., Kuravsky M.L., Bragina E.E., Kurilo L.F., Khayat S.S., Sukhomlinova M.Y., Schmalhausen E.V. Detection of a mutation in the intron of Sperm-specific glyceraldehyde-3-phosphate dehydrogenase gene in patients with fibrous sheath dysplasia of the sperm flagellum. Andrologia. 2017; 49(2).
- Olszewska M., Barciszewska M.Z., Fraczek M., Huleyuk N., Chernykh V.B., Zastavna D., Barciszewski J., Kurpisz M. Global methylation status of sperm DNA in carriers of chromosome structural aberrations. Asian J Androl. 2017;19(1):117-124.
- Arifulin E.A., Bragina E.E., Kurilo L.F., Sheval E.V. High-throughput analysis of TUNEL-stained sperm using image cytometry. Cytometry A. 2017;91(9):854-858.
- Kurilo L.F. Quantitative methods assessing the meiosis of female and male germ cells. Clinical and experimental morphology, 2018, No. 2, P.4-12.
- Kolomiets O.L., Lelekova A.A., Kashintsova A.A., Kurilo L.F., Bragina E.E., Chernykh V.B., Gablia M.Yu., Vinogradov I.V., Vityazeva I.I., Bogolyubov S.V., Spangenberg V.E. Detection of meiosis and spermatogenesis disorders using light, electron and fluorescence microscopy. Andrology and Genital Surgery 2018, No. 1, p. 12-23.
- Chernykh V.B. Genomic technologies in the diagnosis of sex development disorders, reproductive system and human reproduction development. Medical Genetics 2018, V.17, No. 2 (188). - p. 3-11.
- Oparina N.V., Markova T.V., Svetlichnaya D.V., Avdeychik S.A., Kalinenkova S.G., Chernykh V.B. Intertissue variability of cell lines in X-chromosome mosaicism. In the collection “Molecular Biological Technologies in Medical Practice”. Novosibirsk, 2018. p. 141-149.
- Repina S.A., Krasovsky S.A., Rozhivanov R.V., Sorokina T.M., Shileiko L.V., Shtaut M.I., Kurilo L.F., Shmarina G.V., Adyan T.A., Kashirskaya N.Yu., Polyakov A.V., Chernykh V.B. Andrological examination of patients with pulmonary and mixed forms of cystic fibrosis. Andrology and Genital Surgery. 2018, No. 2, p. 31-39.
- Safina N.Yu., Yamandi T.A., Chernykh V.B., Akulenko L.V., Bogolyubov S.V., Vityazeva I.I., Ryzhkova O.P., Stepanova A.A., Adyan T.A., Bliznets E.A., Polyakov A.V. Genetic factors of male infertility, their combination and spermological characteristics of men with impaired fertility. Andrology and Genital Surgery. 2018; 19 (2): 40-51.
- Dantsev I.S., Ivkin E.V, Tryakin A.A., Godlevski D.N., Latyshev O.Y., Rudenko V.V., Mikhaylenko D.S., Chernykh V.B., Volodko E.A., Okulov A.B., Loran O.B., Nemtsova M.V. Genes associated with testicular germ cell tumors and testicular dysgenesis in patients with testicular microlithiasis. Asian J Androl. 2018; 20(6): 593-599.
List of Research Theses
Performed in 1986-2018 and supervised by Professor Kurilo L.F., Doctor of biological science
- Terekhova M.N. Clinical and morphofunctional characteristics of the offspring ovarian development during various course of pregnancy. 1994
- Bragina E.E. Patterns of human spermatogenesis disorders in certain genetic and infectious diseases. 2001
- Chernykh V.B. Abnormalities of sex chromosomes in sex development and human reproduction disorders. 2015
- Makarova N.P. Morphological and molecular-biological features of postovulatory oocytes and their role in the preimplantation development of human embryos. 2018
- Ignatieva E.L., Assessment criteria for the development of mammals’ female gametes. 1986.
- Dzhangeldina Z.N. Morphofunctional characteristic of gonads development of Semirechenskaya hybrid breed pigs as compared to wild and domestic pigs of other breeds. 1987
- Teplyakova N.P. Morphological characteristics and chronology of oogenesis and folliculogenesis in the cattle ovaries. 1987
- Khilkevich L.V. Assessment criteria for the damaging effect of exogenous factors on spermatogenesis of humans and mammals. 1991
- Dzhgarkava N.A. Study of chromosomal abnormalities in mitosis and meiosis in men with infertility associated with impaired spermatogenesis. 1991
- Shileiko L.V. Some features of spermatogenesis and comparative spermatology of pulmonary terrestrial mollusks Trichia hispida and Succinea putris. 1995
- Gaeva T.N. Development of a quantitative analysis method for the ejaculate immature germ cells and determining its information value. 1997
- Sharonin V.O. The role of molecular cytogenetic studies of chromosomal abnormalities in somatic and germ cells in the male patients’ reproductive system. 1998
- Savelieva A.P. The structure of chromosomal abnormality among patients with male infertility and pathozoospermia. 2002
- Chernykh V.B. Microdeletion analysis of the AZF locus as a part of comprehensive clinical genetic examination of men with azoospermia and oligozoospermia. 2002
- Glinkina Zh.I. Medical and genetic aspects of infertile couples examination included in IVF & ET, ICSI program. 2003.
- Grishina E.M. Characteristics of spermatogenesis in some genetically determined and acquired reproductive disorders in men. 2004
- Borkina P.A. Social hygienic study of the use of biomedical technologies to optimize the reproductive health of the population. 2004
- Sorokina T.M. The structure of hereditary pathology in individuals with impaired formation and/or functioning of the reproductive system. 2006.
- Makarova N.P. Morphological analysis of spermatogenesis under the new anti-tumor drugs and low-intensity laser radiation as a radioprotector. 2006
- Jambor V.V. Improvement to the human in vitro fertilization program using the vitrification method. 2006
- Shuliak I.Yu. Folliculogenesis in various forms of endometriosis. 2009
- Zhakhur N.A. Differentiated approaches to the management of patients with premature ovarian failure. 2011
- Khayat S.Sh. Ultrastructural and molecular genetic characterization of spermatozoa in patients with asthenozoospermia. 2012.
- Gordeeva E.G. The frequency of chromosomes meiotic nondisjunction in men with impaired reproductive function. 2013
- Goncharova N.N. Comprehensive clinical, genetic diagnosis and therapy of infertility in the married couple. 2013
- Denisenko M.V. Diagnostic and prognostic value of the oocyte follicular system state in assessing the ovarian reserve. 2018.
Educational work is carried out in the above fields. Lectures are being given to the postgraduate students and residents of the postgraduate study and residency department of FSBI RCMG, physicians-students of the Medical Genetics Department of Russian Medical Academy of Continuous Professional Education, medical students (N.I. Pirogov Moscow State Medical University, I.M. Sechenov First Moscow State Medical University, A.I. Evdokimov Moscow State Medical Dental University, RUDN), medical schools in Moscow. Scientific and methodological advising and training of specialists in Moscow and other cities countrywide (geneticists, andrologists, urologists, gynecologists, endocrinologists, specialists in the field of medical reproductive medicine) are being carried out.