Department of Physiology and Cell Biiology

 

 

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Wei Yan, M.D., Ph. D.

Associate Professor

Scanning electron microscopic images of sperm from wild-type (left) and Spem1-null (right) mice. Scale bar = 10µm (Photo by Wei Yan).

Regulation of Mammalian Gametogenesis

We are interested in how gametes, sperm and oocytes, are produced in mammals. In particular, we investigate which of the germ cell-specific genes are essential for successful production of gametes and which particular molecular pathways they are involved in. We utilize gene knockout technologies and molecular biology approaches to define physiological roles of these genes and the molecular mechanisms by which they regulate germ cell development. Currently, our efforts are focused on the following three topics: (1) the regulation of protein turnover by ubiquitination during spermiogenesis; (2) the control of cytoplasm removal during sperm individualization and spermiation (sperm release); (3) physiological roles of germ cell-specific small non-coding RNAs. Our study is important not only for the identification of causative genes of human infertility, but also for the development of non-hormonal contraceptives.

 

Search For Dr Yan's Publications In PubMed

Selected Publications

  1. Yan W, Suominen J, Toppari J (2000) Stem cell factor protects germ cells from apoptosis in vitro. Journal of Cell Science 113:161-168
  2. Yan W, Kero J, Huhtaniemi I, Toppari J (2000) Stem cell factor functions as a survival factor for mature Leydig cells and a growth factor for precursor Leydig cells after ethylene dimethane sulfonate treatment: implication of the role of stem cell factor/c-kit interaction in Leydig cell development. Developmental Biology 227:169-182
  3. Yan W, Kero J, Suominen J, Toppari J (2001) Differential expression and regulation of retinoblastoma protein (pRb) family members during testicular development and spermatogenesis: a model for the control of germ cell proliferation, differentiation and apoptosis in vivo. Oncogene  20: 1343–1356
  4. Yan W, Assadi AH, Wynshaw-Boris A, Eichele G, Matzuk MM, Clark GD (2003) A novel role for platelet-activating factor acetylhydrolase 1b in mouse spermatogenesis. Proceedings of the National Academy of Sciences USA 100:7189-7194.
  5. Yan W, Huang JX, Lax AS, Pelliniemi L, Salminen E, Poutanen M, Toppari J (2003) Overexpression of Bcl-w in the testis disrupts spermatogenesis: revelation of a role of BCL-W in male germ cell cycle control. Molecular Endocrinology 17:1868-1879.
  6. Yan W, Ma L, Burns KH, Matzuk MM (2003) Identification of a novel spermatid-specific linker histone H1 involved in chromatin remodeling during mammalian spermiogenesis. Proceedings of the National Academy of Sciences USA 100:10546-10551.
  7. Yan W, Ma L, Burns, KH, Matzuk MM (2004) Haploinsufficiency of KLHL10 causes male infertility. Proceedings of the National Academy of Sciences USA 101:7793-7798.
  8. Yan W, Ma L, Stein P, Pangas SA, Burns KH, Bai, YC, Schultz, RM,, Matzuk, MM (2005) Mice deficient in oocyte-specific oligoadenylate synthetase-like protein OAS1D display reduced fertility. Molecular and Cellular Biology 25:4615-4624.
  9. Jin JL, O’Doherty AM, Wang SH, Zheng HL, Sanders KM, Yan W (2005) Catsper3 and Catsper4 encode two cation channel-like proteins exclusively expressed in the testis. Biology of Reproduction 73:1235-1242
  10. Greenbaum MP, Yan W*, Wu MH, Lin YN, Agno JE, Sharma M, Braun RE, Rajkovic A, Matzuk MM. (2006) TEX14 is essential for intercellular bridges and fertility in male mice. Proceedings of the National Academy of Sciences USA 103(13):4982-7. (*co-first authors)
  11. Wang SH, Zheng HL, Esaki Y, Kelly F, Yan W (2006) Cullin3 is a KLHL10-interacting protein preferentially expressed during late spermiogenesis. Biology of Reproduction 74:102-108
  12. Ro S, Park C, Jin J, Sanders KM, Yan W (2006) A PCR-based method for detection and quantification of small RNAs. Biochemical and Biophysical Research Communications 351:756-763.
  13. Zheng H, Stratton CJ, Morozumi K, Jin J, Yanagimachi R, Yan W (2007) Lack of Spem1 causes aberrant cytoplasm removal, sperm deformation and male infertility. Proceedings of the National Academy of Sciences USA  104:6852-6857
  14. Jin J, Jin N, Zheng H, Ro S, Tafolla D, Sanders KM, Yan W (2007) Catsper3 and Catsper4 are Essential for Sperm Hyperactivated Motility and Male Fertility. Biology of Reproduction 77:37-44
  15. Ro S, Park C, Song R, Nguyen D, Jin J, Sanders KM, McCarrey JR, Yan W (2007) Cloning and expression profiling of testis-expressed piRNA-like RNAs. RNA   Published August 13, 2007, 10.1261/rna.640307 Download Supplementary Tables Here
  16. Zheng Z, Zheng H, Yan W (2007) Fank1 is a testis-specific gene encoding a nuclear protein exclusively expressed during the transition from the meiotic to the haploid phase of spermatogenesis. Gene expression patterns 7:777-783
  17. Ro S, Park C, Young D, Sanders KM, Yan W (2007) Tissue-dependent paired expression of miRNAs. Nucleic Acids Research  Published online on August 28, 2007, Doi:10.1093/nar/gkm641
  18. Lin YN, Roy A, Yan W, Burns KH, Matzuk MM (2007) Loss of zona pellucida binding proteins in the acrosomal matrix disrupts acrosome biogenesis and sperm morphogenesis. Molecular and Cellular Biology doi:10.1128/MCB.01029-07, published online ahead of print on 30 July 2007
  19. Ro S, Park C, Young D, Sanders KM, McCarrey JR, Yan W (2007) Cloning and expression profiling of testis-expressed microRNAs Developmental Biology311: 604-614
  20. Ro S, Song R, Park C, Zheng H, Sanders KM, Yan W (2007) Cloning and expression profiling of small RNAs expressed in the mouse ovary. RNA   Published online before print October 19, 2007, DOI: 10.1261/rna.754207. Download supplementary data from Here!
  21. Yan W*, Morozumi K*, Zhang J, Ro S, Park C, Yanagimachi R (2008) Birth of Mice after Intracytoplasmic Injection of Single Purified Sperm Nuclei and Detection of Messenger RNAs and MicroRNAs in the Sperm Nuclei. Biology of Reproduction  78:896-902 (* corresponding author)
  23. Song R, Ro S, Michaels JD, Park, C, McCarrey JR, Yan W (2009) Many X-linked microRNAs escape meiotic sex chromosome inactivation. Nature Genetics41:488-493
  24. Yan W (2009) Male Infertility caused by spermiogenic defects: Lessons from gene knockouts. Molecular and Cellular Endocrinology doi:10.1016/j.mce.2009.03.003

University of Nevada
University of Nevada, Reno
Maintained by: Treg A. Gardner, M.S.
Last Modified: 04/07/09