Participating Faculty

Michael Griswold

Michael D. Griswold

Department:School of Molecular Biosciences, WSU
Credentials:1969 - Ph.D., University of Wyoming
Office:Biotech Lsf 247
Phone:509-335-6281
Fax:509-335-4159
Mailing Address:Washington State University
PO Box 647520
Pullman, WA 99164-7520
E-mail:mgriswold@wsu.edu
Website:Click here


Research Interests

Spermatogenesis

Research Summary

Normal fertility in the male requires the constant production of large numbers of gametes over a long time period. Spermatogenesis is a very complex, highly organized and regulated process that involves mitosis, meiosis and unique pathways of differentiation. In general, spermatogenesis involves three major biological fundamentals: (a) the renewal of stem cells and the production and expansion of progenitor cells (mitosis) (b) the reduction, by one-half, of the chromosome numbers in progenitor cells (meiosis) and (c) the unique differentiation of haploid cells (spermiogenesis). Early progenitor cells or spermatogonia are defined as “undifferentiated” or A spermatogonia in the mouse. Once the spermatogonia enter the “differentiation” pathway they begin the series of differentiation steps leading to meiosis and spermiogenesis. The endocrine regulation of spermatogenesis occurs by the interplay of gonadotropins and steroids with the somatic cells of the seminiferous tubules (Sertoli cell and Leydig cells) and of vitamin A directly with the germinal cells.

The research in my laboratory has been directed towards the understanding of mammalian spermatogenesis at the molecular level. Our current studies are focused on the role of vitamin A in this process. In particular we are interested in the mechanisms by which retinoic acid (vitamin A) influences the commitment of germ cells to enter meiosis. These mechanisms are central to the timing of sperm production and the organization of gametogenesis.

In our initial approach we developed extensive mRNA and microRNA expression data bases for both germ cells and somatic cells in the testis using array technology and we are currently enhancing that information using next generation sequencing. Our databases cover nearly all aspects of spermatogenesis including cell specific expression and hormone responsive transcription and are used by investigators worldwide. Our latest emphasis has been on discovering the genes expressed in germ cells that enable the entry of these cells into meiosis. We then examine the role of these genes using a variety of genetic approaches with transgenic mice. The projects span the disciplines from biochemistry to genetics to cell biology.

Research Publications

Griswold, M and Hogarth, C (2018) Beyond Stem Cells: The Commitment of Progenitor Cells to Meiosis. Stem Cell Research (2018) (in press)

Griswold, M. (2018) The Spermatogenic Cycle in The Encyclopedia of Reproduction, Second edition (Flaws, J., Jegou, B.,McCarrey, J.,Niederberger, C., Simon, C., Skinner, M., Spencer, T., Swanson, P., and Yan, W., eds.) vol. 3 Gametogenesis, Fertilization and Early Development (in press)

Griswold, M. (2018) Energetic of germ cells in The Encyclopedia of Reproduction, Second edition (Flaws, J., Jegou, B.,McCarrey, J.,Niederberger, C., Simon, C., Skinner, M., Spencer, T., Swanson, P., and Yan, W., eds.) vol. 3 Gametogenesis, Fertilization and Early Development (in press)

Griswold, M. (2018) Molecular biology of Sertoli cells in The Encyclopedia of Reproduction, Second edition (Flaws, J., Jegou, B.,McCarrey, J.,Niederberger, C., Simon, C., Skinner, M., Spencer, T., Swanson, P., and Yan, W., eds.) vol. 3 Gametogenesis, Fertilization and Early Development (in press)

Griswold M. Male Germ Cell Differentiation. In: Encyclopedia of Endocrine Diseases, 2e (Hutaniemi, I. Ed) Elsevier Inc. in Press
Jauregui, E., Mitchell, D., Garza, S., Topping, T., Hogarth, C. and Griswold, M. (2018) Leydig cell genes change their expression and association with polysomes in a stage-specific manner in the adult mouse testis Biology of Reproduction in press

Jauregui, E., Mitchell, D., Garza, S., Topping, T., Hogarth, C. and Griswold, M. (2018) Retinoic acid receptor signaling is necessary in Leydig Cells for normal spermatogenesis. Differentiation in press

Griswold, M. (2018) 50 years of Spermatogenesis: Sertoli cells and their Interactions with Germ Cells.  Biol Reprod 50th anniversary issue  in press.

NewkirkS.J., Leea S., Grandib FC, Gaysinskayac V, Rosserb JM, Vanden Berg N,Hogarth CA, Marchetto MCN, Muotri AR, Griswold MD, Yee P, Bortvin A, Gage, FH, Boeke JD, An W,  The intact piRNA pathway prevents L1 mobilization in male meiosis (2017) Proc Nat Acad Sci 11:114(28): E5635-E5644.   PMCID: PMC5514719

Agrimson KS, Oatley MJ, Mitchell D, Oatley JM, Griswold MD and Hogarth CA (2017)  Retinoic acid deficiency leads to an increase in spermatogonial stem number in the neonatal mouse testis. Dev Biol. 2017 Dec 15;432(2):229-236. doi: 10.1016/j.ydbio.2017.10.002. Epub 2017 Oct 14. PMID:29037932  PMCID: PMC5736010

Beedle M, Hogarth CA, and Griswold MD (2017) Role of Retinoic Acid Signaling in the Differentiation of Spermatogonia. In: The Biology of mammalian Spermatogonia, Oatley, J and Griswold M Eds, 133-146 Springer Nature, New York. 

Griswold, M. D. (2016). "Spermatogenesis: The Commitment to Meiosis." Physiol Rev 96(1): 1-17. PMID: 26537427

França LR, Hess RA, Dufour JM, Hofmann MC, Griswold MD. (2016) The Sertoli cell: one hundred fifty years of beauty and plasticity. Andrology. 2016 Mar;4(2):189-212. doi: 10.1111/andr.12165. Review. PMID: 26846984  PMCID: in process

Chen Y, Ma L, Hogarth C, Wei G, Griswold MD, Tong MH. (2016) Retinoid signaling controls spermatogonial differentiation by regulating expression of replication-dependent core histone genes. Development. 2016 May 1;143(9):1502-11. 

Agrimson KS, Onken J, Mitchell D, Topping TB, Chiarini-Garcia H, Hogarth CA, Griswold MD. (2016) Characterizing the Spermatogonial Response to Retinoic Acid During the Onset of Spermatogenesis and Following Synchronization in the Neonatal Mouse Testis.  Biol Reprod. 2016 Oct;95(4):81. PMID: 27488029 PMCID: PMC5176362

Kent, T., et al. (2016). "ALDH Enzyme Expression Is Independent of the Spermatogenic Cycle, and Their Inhibition Causes Misregulation of Murine Spermatogenic Processes." Biol Reprod 94(1): 12.Arnold, S. L., et al. (2015). "Pharmacological inhibition of ALDH1A in mice decreases all-trans retinoic acid concentrations in a tissue specific manner." Biochem Pharmacol 95(3): 177-192.

Arnold, S. L., et al. (2015). "Importance of ALDH1A enzymes in determining human testicular retinoic acid concentrations." J Lipid Res 56(2): 342-357.

Hogarth, C. A., et al. (2015). "Processive pulses of retinoic acid propel asynchronous and continuous murine sperm production." Biol Reprod 92(2): 37.

Hogarth, C. A., et al. (2015). "CYP26 Enzymes Are Necessary Within the Postnatal Seminiferous Epithelium for Normal Murine Spermatogenesis." Biol Reprod 93(1): 19.

Koubova, J., et al. (2014). "Retinoic acid activates two pathways required for meiosis in mice." PLoS Genet 10(8): e1004541.

Arnold, S. L., et al. (2015). "Importance of ALDH1A enzymes in determining human testicular retinoic acid concentrations." J Lipid Res 56(2): 342-357.

Hogarth, C. A., et al. (2015). "Processive pulses of retinoic acid propel asynchronous and continuous murine sperm production." Biol Reprod 92(2): 37.




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