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      The Unique Mechanisms of Cellular Proliferation, Migration and Apoptosis are Regulated through Oocyte Maturational Development—A Complete Transcriptomic and Histochemical Study

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          Abstract

          The growth and development of oocyte affect the functional activities of the surrounding somatic cells. These cells are regulated by various types of hormones, proteins, metabolites, and regulatory molecules through gap communication, ultimately leading to the development and maturation of oocytes. The close association between somatic cells and oocytes, which together form the cumulus-oocyte complexes (COCs), and their bi-directional communication are crucial for the acquisition of developmental competences by the oocyte. In this study, oocytes were extracted from the ovaries obtained from crossbred landrace gilts and subjected to in vitro maturation. RNA isolated from those oocytes was used for the subsequent microarray analysis. The data obtained shows, for the first time, variable levels of gene expression (fold changes higher than |2| and adjusted p-value < 0.05) belonging to four ontological groups: regulation of cell proliferation (GO:0042127), regulation of cell migration (GO:0030334), and regulation of programmed cell death (GO:0043067) that can be used together as proliferation, migration or apoptosis markers. We have identified several genes of porcine oocytes ( ID2, VEGFA, BTG2, ESR1, CCND2, EDNRA, ANGPTL4, TGFBR3, GJA1, LAMA2, KIT, TPM1, VCP, GRID2, MEF2C, RPS3A, PLD1, BTG3, CD47, MITF), whose expression after in vitro maturation (IVM) is downregulated with different degrees. Our results may be helpful in further elucidating the molecular basis and functional significance of a number of gene markers associated with the processes of migration, proliferation and angiogenesis occurring in COCs.

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          Most cited references50

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          Helix-Loop-Helix Proteins: Regulators of Transcription in Eucaryotic Organisms

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            Oocyte-somatic cell interactions during follicle development in mammals.

            Our current perspectives on the relationship between the oocyte and its surrounding somatic cells are changing as we gain a greater understanding of factors regulating folliculogenesis. It is now widely accepted that the oocyte plays a very active role in promoting follicle growth and directing granulosa cell differentiation. The oocyte achieves this, in part, by secreting soluble paracrine growth factors that act on its neighboring granulosa cells, which in turn regulate oocyte development. In preantral follicles, the oocyte directs granulosa cells to regulate oocyte growth, and oocytes may also directly drive follicle growth. In antral follicles, the oocyte governs the behaviour of cells in its immediate vicinity, thereby actively regulating its own microenvironment. As such, the oocyte establishes and maintains the distinct cumulus lineage of granulosa cells. This oocyte-cumulus cell interaction, in general, prevents luteinization of cumulus cells by promoting growth, regulating steroidogenesis and inhibin synthesis, and suppressing luteinizing hormone receptor expression. Conversely, mural granulosa cells in antral follicles, which have no direct physical contact with the oocyte and, presumably, experience a more diffuse concentration of oocyte-secreted factors, proceed to a different phenotype. In the ovulating follicle, oocyte-secreted factors also play vital roles in enabling cumulus cell expansion and regulating extracellular matrix stability, thus facilitating ovulation. The identities of these oocyte-secreted growth factors regulating such key ovarian functions remain unknown, although growth differentiation factor-9 (GDF-9), GDF-9B and/or bone morphogenetic protein-6 (BMP-6) are likely candidate molecules, probably forming complex local interactions with other related members of the transforming growth factor-beta (TGF-beta) superfamily. Elucidating the nature of oocyte-somatic cell interactions at the various stages of follicle development will have important implications for our understanding of factors regulating folliculogenesis, ovulation rate and fecundity.
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              Human female meiosis: what makes a good egg go bad?

              Critical events of oogenesis occur during three distinct developmental stages: meiotic initiation in the fetal ovary, follicle formation in the perinatal period, and oocyte growth and maturation in the adult. Evidence from studies in humans and mice suggests that the genetic quality of the egg may be influenced by events at each of these stages. Recent experimental studies add additional complexity, suggesting that environmental influences might adversely affect all three stages. Thus, understanding the molecular control of oogenesis during these critical developmental windows will not only contribute to an understanding of human aneuploidy, but also provide a means of assessing potential effects of environmental exposures on human reproductive health.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                26 December 2018
                January 2019
                : 20
                : 1
                : 84
                Affiliations
                [1 ]Division of Infertility and Reproductive Endocrinology, Department of Gynecology, Obstetrics and Gynecological Oncology, Poznan University of Medical Sciences, 60-535 Poznań, Poland; blazej.chermula@ 123456wp.pl (B.C.); maciejbrazert@ 123456ump.edu.pl (M.B.); katarzyna.ozegowska@ 123456ump.edu.pl (K.O.); pawelczyk.leszek@ 123456ump.edu.pl (L.P.)
                [2 ]Department of Obstetrics and Gynecology, University Hospital and Masaryk University, 601 77 Brno, Czech Republic; jeseta@ 123456gmail.com
                [3 ]Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznań, Poland; psujka@ 123456ump.edu.pl (P.S.-K.); akonwer@ 123456ump.edu.pl (A.K.); pcelichowski@ 123456ump.edu.pl (P.C.); jbudna@ 123456ump.edu.pl (J.B.-T.); mnowicki@ 123456ump.edu.pl (M.N.)
                [4 ]Department of Anatomy, Poznan University of Medical Sciences, 60-781 Poznań, Poland; abryja@ 123456ump.edu.pl (A.B.); wkranc@ 123456ump.edu.pl (W.K.); m.jankowski.14@ 123456aberdeen.ac.uk (M.J.); mjnawrocki@ 123456ump.edu.pl (M.J.N.); ikocherova@ 123456ump.edu.pl (I.K.); blanka.maria.b@ 123456gmail.com (B.B.); malgorzatapopis111@ 123456gmail.com (M.P.); mbruska@ 123456ump.edu.pl (M.B.)
                [5 ]Veterinary Center, Nicolaus Copernicus University in Torun, 87-100 Toruń, Poland; pantosik@ 123456umk.pl (P.A.); dbukowska@ 123456umk.pl (D.B.); prof.bruessow@ 123456gmail.com (K.P.B.)
                [6 ]Department of Histology and Embryology, Wroclaw University of Medical Sciences, 50-368 Wrocław, Poland; mazab@ 123456ump.edu.pl
                [7 ]Division of Anatomy and Histology, University of Zielona Gora, 65-046 Zielona Góra, Poland
                Author notes
                [* ]Correspondence: bkempisty@ 123456ump.edu.pl ; Tel./Fax: +48-61-8546418 or +48-61-8546440
                Author information
                https://orcid.org/0000-0001-9476-0235
                https://orcid.org/0000-0003-3753-755X
                Article
                ijms-20-00084
                10.3390/ijms20010084
                6337548
                30587792
                22849ad8-9804-4eef-8e97-ce0a5d42ce39
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 05 November 2018
                : 21 December 2018
                Categories
                Article

                Molecular biology
                pig,oocytes,microarray,cellular competence
                Molecular biology
                pig, oocytes, microarray, cellular competence

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