Skinner, Mike
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Center for Reproductive Biology

MBioS 401/501

Research Interests

Research is focused on the molecular and cellular aspects of reproduction, with emphasis in the area of testis and ovary cell biology. The cells of interest and specific interactions investigated have an integral role in controlling the development of the spermatozoa and oocyte. Our observations indicate that the mesenchymal cells of both the testis and ovary produce inducer substances that alter the differentiation and function of adjacent epithelial cells. The role that reproductive hormones (e.g. steroids) and growth factors (e.g. transforming growth factors, neurotropins) have in regulating these mesenchymal-epithelial cell interactions is under investigation. The characterization and molecular cloning of mesenchymally-derived inducer substances is in progress, as well as an investigation of the molecular and cellular pharmacology of these factors. How these factors promote the transcriptional regulation of cellular differentiation is being investigated through an analysis of the role of a unique class of transcription factors, basic-helix-loop-helix (bHLH) factors.  Information obtained from these studies is necessary before novel therapeutic agents can be designed and targeted at reproductive cells for the prevention of infertility or to act as contraceptives. The research is designed to understand the cell biology of the testis and ovary on a molecular level, as well as provide insight into the mechanisms regulating the cellular functions and cell-cell interactions in other organs. Abnormal expression of these mesenchymal factors is postulated to be associated with the carcinogenesis of these tissues (e.g. ovarian cancer). A hypothesis being examined is that a family of mesenchymal inducer factors exist that are essential for epithelial cell differentiation during development and maintenance of cellular differentiation in the adult.

Publications

Nilsson, E, Westfall, S., Sadler-Riggleman, I, Larsen, T, McDonald, C, and MK Skinner (2002) An In Vivo Mouse Reproter Gene (Human seccreted Alkaline Phosphatase) Model to Monitor Ovarian Tumor Growth and Response to Therapeutics. Cancer Chemo & Pharmacology 49:93-100.

Chaudhary J. and Skinner, M.K. (2002) Identification of a Novel Gene Product SERZ that is Important for Follicle Stimulating Hormone Activation of Testicular Sertoli Cells. Endocrinology 143:426-435.

Nilsson, E., Kezele, P. and Skinner, M.K. (2002) Leukemia Inhibitory Factor (LIF) Induces the Primordial to Primary Follicle Transition in Rat Ovaries. Molecular and Cellular Endocrinology 188:65-73.

Uzumcu M, Dirks K. and Skinner, M.K. (2002) Inhibition of platelet-derived growth factor (PDGF) actions in the embryonic testis influences normal cord development and morphology. Biology of Reproduction 66:7445-753.

Cupp A, Tessarrolo L. and Skinner, M.K. (2002) Testis development phenotypes in neurotropin receptor trkA and trkC null mutations: role in seminiferous cord formation and germ cell survival. Biology of Reproduction 66:1838-1845.

Kezele P.R., Nilsson, E.E., and MK Skinner (2002) Insulin But Not Insulin-like Growth Factor – 1 Promotes the Primordial to Primary Follicle Transition. Molecular and Cellular Endocrinology 192:37-43.

Nilsson E and MK Skinner (2002) GDF-9 Stimulates progression of primary but not primordial ovarian follicle development. Biology of Reproduction 67:1018-1024.

Uzumcu M, Westfall S, Dirks K and MK Skinner (2002) Embryonic Testis Cord formation and mesonephric cell migration requires the phosphotidylinositol 3-kinase (PI3K) Signaling Pathway. Biology of Reproduction 67:1927-1935.

Devine PJ, Sipes EG, Skinner, MK and P. Hoyer (2002) Characterization of a Rat In Vitro Ovarian Culture System to Study the Ovarian Toxicant 4-Vinylcyclohexene Diepoxide. Toxicology and Applied Pharmacology 184:107-115.

Kezele P, Nilsson EE and MK Skinner (2002) Cell-Cell Interactions in Primordial Follicle Assembly and Development. Frontiers in Bioscience 7:1990-1996.

Nilsson EE and MK Skinner (2002) Role of Transforming Growth Factor Beta in Ovarian Surface Epithelium Biology and Ovarian Cancer. Reproductive Bio-Medicine Online 5(3):254-258.

Skinner MK (2003) Cell-Cell Signaling in the Testis and Ovary. In: Handbook of Cell Signaling (Ralph A Bradshaw and Edward Dennis, eds.) Academic Press/Elsevier Science Publishing. Vol 3, chapter 342, pp 531-534.

Nilsson EE, Doraiswamy V, and MK Skinner (2003) Transforming Growth Factor-Beta (TGFb1, TGFb2 and TGFb3) expression during bovine ovarian antral follicle development. Molecular Reproduction and Development 66:237-246.

Kezele P and MK Skinner (2003) Regulation of ovarian primordial follicle assembly and development by estrogen and progesterone: endocrine model of follicle assembly. Endocrinology 144:3329-3337.

Cupp, A.S., Uzumcu, M, Phillips, B, Dirks, K, and MK Skinner (2003) Effect of Transient Embryonic In Vivo Exposure of the Endocrine Disruptor Methoxychlor on Embryonic and Postnatal Testis Development and Function. Journal of Andrology 24(5): 736-745.

Cupp AS, Uzumcu, M, and MK Skinner (2003) Chemotactic Role of Neurotropin 3 in the embryonic testis that facilitates morphological male sex determination. Biology of Reproduction 68:2033-2037.

Nilsson EE and MK Skinner (2003)  Bone Morphogenetic Protein –4 acts as an ovarian follicle survival factor and promote primordial follicle development.   Biology of Reproduction 69:1265-1272.

Chaudhary, J., Sadler-Riggleman, I and Skinner, M.K. (2004) Identification of a novel Sertoli cell gene product SERT that influences follicle stimulating hormone actions.  Gene 324:79-88.

Nilsson EE and MK Skinner (2004)  Kit ligand and basic fibroblast growth factor interactions in the induction of ovarian primordial to primary follicle transition.   Molecular and Cellular Endocrinology 214:19-25.

Saxlund MA, Sadler-Riggleman I, and MK Skinner (2004) Role of Basic Helix-Loop-Helix (bHLH) and CREB Transcription Factors in the Regulation of Sertoli Cell Androgen Binding Protein Expression.  Molecular Reproduction and Development 68:269-278.

Uzumcu M, Suzuki H, and MK Skinner (2004) Effect of the Anti-Androgenic Endocrine Disruptor Vinclozolin on Embryonic Testis Cord Formation and Postnatal Testis Development and Function.  Reproductive Toxicology 18:765-774.

Chaudhary J, Sadler-Riggleman I and MK Skinner (2005) The Helix-Loop-Helix Inhibitor of Differentiation (Id) Proteins Induce Post-Mitotic Terminally Differentiated Sertoli Cells to Re-Enter the Cell Cycle and Proliferate. Biology of Reproduction 72:1205-1217.

Kezele PR, Ague J, Nilsson EE and MK Skinner (2005)  Alterations in the ovarian transcriptome during primordial follicle assembly and development.  Biology of Reproduction 72:241-255.

Cupp, A.S. and Skinner, M.K.   (2005) Embryonic Sertoli Cell Differentiation.  In:  Sertoli Cell Biology eds. M.D. Griswold and M.K. Skinner, Elsevier -Academic Press, San Diego, CA, pp. 43-70.

Skinner, M.K.  (2005) Sertoli Cell Secreted Regulatory Factors.  In:  Sertoli Cell Biology eds. M.D. Griswold and M.K. Skinner, Elsevier -Academic Press, San Diego, CA, pp. 107-120.

Chaudhary, J. and Skinner, M.K.   (2005) Transcription Factors in Sertoli Cells.  In:  Sertoli Cell Biology eds. M.D. Griswold and M.K. Skinner, Elsevier -Academic Press, San Diego, CA, pp. 251-280.

Skinner, M.K.   (2005) Sertoli Cell-Somatic Cell Interactions.  In:  Sertoli Cell Biology eds. M.D. Griswold and M.K. Skinner, Elsevier -Academic Press, San Diego, CA, pp. 317-328.

Small CL, Shima JE, Uzumcu M,Skinner MK and MD Griswold (2005) Profiling gene expression during the differentiation and development of the murine embryonic gonad.  Biology of Reproduction 72:492-501.

Ojeda S and MK Skinner (2005) Puberty in the rat.  In Encyclopedia of Reproduction, eds. Knobil & Neil, Elsevier – Academic Press, San Diego, CA.

Ye X, Hama K, Contos J, Anliker B, Inoue A, Skinner MK, Suzuki H Amano T, Kennedy G, Arai H, Aoki J and Chun J.  (2005) LPA3-mediated lysophosphatidic acid signaling in implantation and embryo spacing. Nature 435:104-108.

Anway M, Cupp AS, Uzumcu M and MK Skinner  (2005)  Epigenetic transgenerational actions of endocrine disruptors and male fertility.  Science  308:1466-1469.  

Meachem SJ, Ruwanpura SM, Ziolkowski J, Ague J, Skinner MK and KL Loveland.  (2005) Developmentally distinct in vivo effects of FSH on proliferation and apoptosis during testis maturation.  Journal of Endocrinology 186:429-446.

Muir T, Sadler-Riggleman I, Stevens JD, and MK Skinner (2005) Role of the basic helix-loop-helix protein ITF2 in the hormonal regulation of Sertoli Cell Differentiation.  Molecular Reproduction and Development 73:491-500.

Muir T, Sadler-Riggleman I, Stevens JD, and MK Skinner (2005) Role of the basic helix-loop-helix transcription factor, scleraxis, in the regulation of Sertoli cell function and differentiation.  Molecular Endocrinology.19:2164-2174.

Westfall S, and MK Skinner (2005) Inhibition Of Phosphatidylinositol 3-Kinase (PI3K) Sensitizes Ovarian Cancer Cells To Carboplatin And Allows Adjunct Chemotherapy Treatment.  Molecular Cancer Therapeutics 4:1764-1771.

Kezele P, Nilsson EE and MK Skinner (2005) Keratinocyte growth factor acts as a mesenchymal factor to promote ovarian primordial to primary follicle transition.  Biology of Reproduction 73:967-973.

Skinner MK. (2005) Regulation of primordial follicle assembly and development.  Hum Reprod Update. 11:461-71.

Anway MD, Memon M, Uzumcu M, and MK Skinner (2006) Transgenerational effect of the endocrine disruptor vinclozolin on male spermatogenesis.  Journal of Andrology 27:868-879.

Skinner MK and Anway MD (2006) Seminiferous cord formation and germ cell programming: epigenetic transgenerational actions of endocrine disruptors.  Annals New York Academy of Science 1061:18-32.

Anway MD, Leathers C and MK Skinner (2006) Endocrine Disruptor Vinclozolin Induced Epigenetic Transgenerataional Adult Onset Disease.  Endocrinology 147:5515-5523.

Chang HS, Anway MD, Rekow SS, and Skinner MK (2006) Transgenerational Epigenetic Imprinting of the Male Germ-Line by Endocrine Disruptor Exposure During Gonadal Sex Determination. Endocrinology 147:5524-5541

Nilsson EE, Stanfield J, and MK Skinner (2006) Interactions between progesterone and tumor necrosis factor-alpha in the regulation of primordial follicle assembly.  Reproduction 132:877-886.

Nilsson EE, Detzel C, and MK Skinner (2006) Platelet-derived growth factor modulates the primordial to primary follicle transition in rat ovaries.  Reproduction 131:1007-1015.

Skinner MK (2006) Epigenetic transgenerational actions of endocrine disruptors through the male germ-line. In: Male-Mediated Development Toxicology.  Ed. D. Anderson and MH Brinkworth, Royal Society of Chemistry, Cambridge, UK, CH001, pp. 1-4.

Anway, MD and MK Skinner (2006) Epigenetic Transgenerational Actions of Endocrine Disruptors.  Endocrinology 147:S43-S49.

Muir T, Wilson-Rawls J, Stevens JD, Rawls A, Kang C and MK Skinner (2007) Integration of CREB and bHLH transcriptional Pathways through heterodimerization of the proteins.  Journal of Biological Chemistry (Submitted)

Westfall S, Nilsson EE and MK Skinner (2007) Role of triptolide as an adjunct chemotherapy for ovarian cancer.  Chemotherapy (Submitted).

Hahn KL, Beres BJ, Howard S, Rowton MJ, Greenbank A, Skinner MK, Chang Y, Rawls A, and J Wilson-Rawls (2007) A deficiency of Lunatic fringe is associated with cystic dilation of the rete testis.  Development (Submitted).

Skinner MK, Schmidt M, Savenkova M, Sadler-Riggleman I, and EE Nilsson. (2007) Regulation of granulosa and theca cell transcriptomes during ovarian antral follicle development.  Biology of Reproduction  (Submitted)

Nilsson EE, Rogers N and MK Skinner (2007) Actions of the anti-müllerian hormone (AMH) on the ovarian transcriptome to inhibit primordial to primary follicle transition.  Reproduction (In Press). 

Jirtle RL and MK Skinner (2007) Environmental Epigenomics and Disease Susceptibility.  Nature Genetics Rev. 8:253-262

Crews D, Gore AC, Hsu TS, Dangleben NL< Spinetta M, Schallert T, Anway MD and Skinner MK (2007) Treansgenerational epigenetic imprints on mate preference.  Proc Natl Acad Sci 104:5942-5946.

Clement TM, Anway MD, Uzumcu M and MK Skinner.  (2007) Regulation of the gonadal transcriptome during sex determination and testis morphogenesis: candidate regulatory genes. Reproduction (Submitted).

Stevens JD, Roalson EH and MK Skinner (2007) Phylogenetic and Microarray Analysis of the basic helix-loop-helix transcription factor family: genomic approach to cellular differentiation. PNAS (Submitted). 

Anway MD and Skinner MK (2007) Epigenetic transgenerational effects of the endocrine disruptor vinclozolin on the prostate transcriptome and adult onset prostate disease.  Endocrinology.  (Submitted)

Skinner MK (2007) What is an epigenetic transgenerational phenotype? F3. Reproductive Toxicology. (Submitted).

Anway MD, Rekow SS, and MK Skinner (2007) Transgenerational epigenetic programming of the testis transcriptome by endocrine disruptor exposure at sex determination.  Endocrinology (Submitted).

Skinner MK (2007) Epigenetic Transgenerational Toxicology and Germ Cell Disease.  International Journal of Andrology.  (Submitted).

Skinner MK (2007) Epigenetic Transgenerational Disease Etiology.  Pediatric Research  (Submitted).