Plenary Lecture

Novel Regulators of Female Reproduction

Professor Alexander V. Sirotkin
Faculty of Natural Sciences
Constantine the Philosopher University in Nitra

Abstract: Development in pharmacology, human and veterinary medicine, assisted reproduction and biotechnology requires search for new regulators of reproductive functions. This is the review of original data concerning the role and application some metabolic hormones (GH, leptin, ghrelin, obestatin), growth factors (IGF-I, IGFBPs, EGF, thrombopoietin), intracellular mediators of their action (cyclic nucleotides, protein kinases, transcription factors and related cDNA, siRNA and miRNA gene constructs) on basic ovarian functions (cell proliferation, apoptosis, secretion, oogenesis, ovulation, production and viability of pups) in different species (pig, rabbit, humans and chicken). Practical applications of some these molecules and their pharmacological and genomical regulators for characterisation, prediction and control of reproductive processes in these species was examined too. It was shown that these hormonal and intracellular regulators are able to control apoptosis, proliferation and secretory activity in human, porcine, rabbit and chicken ovarian cells and maturation of porcine oocytes and cumulus oophorus in vivo and in vitro, as well as to suppress or promote the response of ovarian cells to other hormones (gonadotrophins, IGF-I, ghrelin). Immuno-blockade of these hormones prevented their effects. Effects of hormones on rabbit, human and chicken ovarian cells and on porcine and bovine oocytes were associated with changes in PKA, MAPK and CDK and transcription factors CREB, STAT-1 and p53 in such cells, whilst blockers of these kinases prevented or promoted hormones action. Transfection of porcine and rabbit granulosa cells with gene constructs for these transcription factors affected ovarian cell functions and prevented or reversed hormones action. Down-regulation of approx. 1./3 known protein kinases by specific siRNA constructs resulted not only decrease in accumulation of these kinases within human ovarian granulosa cells, but also changes in expression of kinase-dependent transcription factors, markers of cell proliferation, apoptosis and release of steroid hormones and IGF-I. Transfection of human granulose cells with constructs up and down regulating expression of some miRNAs are able to increase or decrease ovarian cell proliferation, occurrence of apoptosis, as well as the release of progestagen, androgen, estrogen and IGF-I . In-vivo experiments demonstrated that leptin, IGF-I, steroid hormones and some regulators of PKA, MAPK and CDK could be used to predict reproductive efficiency, for direct in-vitro control of maturation of oocytes and for in-vivo stimulation of reproduction in pigs and rabbits. These observations suggest, that metabolic hormones, growth factors and intracellular regulators and mediators of their action (protein kinases, transcription factors, siRNAs, miRNAs) can be used for characterization of state of ovarian cells, for identification signaling pathways (hormones-growth factors-protein kinases-transcription factors-genes regulating proliferation, apoptosis and secretory activity) controlling reproductive processes, as well as for prediction and control of basic ovarian cell functions (proliferation, apoptosis, secretory activity, maturation of oocyte-cumulus complex and fertility).

Brief Biography of the Speaker: Prof. A.V. Sirotkin, PhD, DrSc is working as Professor at the Constantine the Philosopher University, as a Research Scientist at Research Institute of Animal Production in Nitra and as a Visiting Professor at the King Saud University in Ryiadh. He has about 630 publications including 130 full papers in the international journals. He is a member of editorial boards of 4 international journals and a recipient of more than 10 national and international awards.

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