Research Interests:
Three major areas are the focus of the research in Dr. Gerton's laboratory: spermatogenesis, fertilization, and development of mammalian preimplantation embryos.

Several questions are being addressed concerning the cell biology, molecular biology, and biochemistry of spermatogenesis, sperm maturation, and sperm function, concentrating upon the sperm acrosome and flagellum as markers of these developmental processes. When do acrosomal and flagellar components first appear? Are all components of a specific structure (acrosome or flagellum) synthesized at the same time (coincident regulation)? What signals are responsible for targeting components to these developing organelles? What regulates the synthesis (transcription and translation) of these sperm-specific components? What effects do structural changes in acrosomal or flagellar components during epididymal maturation have on their functions?

Several of the major components of the acrosome and sperm tail have been purified and their corresponding cDNAs cloned for studies of protein structure and expression. The deduced amino acid sequences of these proteins have provided new clues concerning the functions of acrosomal and flagellar proteins. One major direction of the laboratory is to study acrosomal and flagellar protein targeting and function in spermatogenic cells and transfected somatic cells using tools of molecular biology and cell biology and to extend these studies to cases of infertility in humans and other species.

Other projects in the laboratory focus upon the functions of proteins identified as components of the sperm acrosome. Two of the acrosomal proteins, AM50 (also know as p50, apexin, Narp, and neuronal pentaxin II) and AM67 (the guinea pig homologue of mouse sperm protein sp56) may be involved in sperm-egg interactions. These studies are leading to a re-evaluation of acrosomal exocytosis. A revised paradigm has been developed that describes acrosomal exocytosis as a continuously variable process with functional intermediates rather a two-step, acrosome-intact/acrosome-reacted, process.

Regarding preimplantation embryo development in mammals, we are studying the function of acrogranin, the precursor of the granulin and epithelin peptides, on mouse embryos. Our results show that acrogranin is an essential growth factor for the development of embryos to the blastocyst stage. A function-blocking anti-acrogranin antibody blocks the development of 8-cell embryos to the blastocyst stage while added exogenous acrogranin stimulates their development.

Recent Representative Publications:
Buffone, M.G., Foster, J.A., Gerton, G.L. (2008) The role of the acrosomal matrix in fertilization. Int. J. Dev. Biol. 52, 511-22.

Buffone, M.G., Zhuang, T., Ord, T.S., Hui, L., Moss, S.B., Gerton, G.L. (2008) Recombinant mouse sperm ZP3-binding protein (ZP3R/sp56) forms a high order oligomer that binds eggs and inhibits mouse fertilization in vitro. J Biol Chem, 283, 12438-45.

Cao, W., Aghajanian, H.K.Seeber, B., Sammel, M.D., Fan, X., Gerton, G.L., Shaunik, A., Chittams, J., and Barnhart, K.T. (2008). Panel of markers can accurately predict endometriosis in a subset of patients. Fertil Steril. 89, 1073-81.

Rodriguez-Miranda, E., Buffone, M.G., Edwards, S.E., Ord, T.S., Lin, L., Sammel, M.D., Gerton, G.L., Moss, S.B., Williams, C.J. (2008) Extracellular adenosine 5'-triphosphate alters motility and improves the fertilizing capability of mouse sperm. Biol Reprod. 79, 164-171.

Zhang, Z., Zariwala, M.A., Mahadevan, M.M., Caballero-Campo, P., Shen, X., Escudier, E., Duriez, B., Bridoux, A.M., Leigh, M., Gerton, G.L., Kennedy, M., Amselem, S., Knowles, M.R., Strauss, J.F., III. (2007) A heterozygous mutation disrupting the SPAG16 gene results in biochemical instability of central apparatus components of the human sperm axoneme. Biol Reprod. 77(5):864-71.

Cheng, Y., Buffone, M. G., Kouadio, M., Goodheart, M., Page, D. C., Gerton, G. L., Davidson, I., and Wang, P. J. (2007). Abnormal sperm in mice lacking the Taf7l gene. Mol Cell Biol. 27, 2582-9.Cao, W., Haig-Ladewig, L., Gerton, G. L., and Moss, S. B. (2006). Adenylate kinases 1 and 2 are part of the accessory structures in the mouse sperm flagellum. Biol Reprod. 75, 492-500.

Cao, W., Gerton, G.L., and Moss S.B. (2006). Proteomic profiling of accessory structures from the mouse sperm flagellum. Mol Cell Proteomics. 5, 801-810.

Nipper, R. W., Jones, B.H., Gerton, G. L., and Moss, S. B. (2006). Protein domains govern the intracellular distribution of mouse AKAP4. (2006). Biol Reprod. 75, 189-96.

Caballero-Campo, P., Chirinos, M., Fan, X.J., Gonzalez-Gonzalez, M.E., Galicia-Chavarria, M., Larrea, F., and Gerton, G.L. (2006). Biological effects of recombinant human zona pellucida proteins on sperm function. Biol. Reprod. 74, 760-8.

Zhang, Z., Kostetskii, I., Tang, W., Haig-Ladewig, L., Sapiro, R., Wei, Z., Patel, A.M., Bennett, J., Gerton, G.L., Moss, S.B., Radice, G.L., and Strauss J.F., III. (2006). Deficiency of SPAG16L causes male infertility associated with impaired sperm motility. Biol. Reprod. 74:751-9.

Jeong, Y. J., Choi, H. W., Shin, H. S., Cui, X. S., Kim, N. H., Gerton, G. L., and Jun, J. H. (2005). Optimization of real time RT-PCR methods for the analysis of gene expression in mouse eggs and preimplantation embryos. Mol Reprod Dev 71, 284-9.

Nipper, R. W., Chennothukuzhi, V., Tutuncu, L., Williams, C. J., Gerton, G. L., and Moss, S. B. (2005). Differential RNA expression and polyribosome loading of alternative transcripts of the Akap4 gene in murine spermatids. Mol Reprod Dev 70, 397-405.

Qin, J., Diaz-Cueto, L., Schwarze, J. E., Takahashi, Y., Imai, M., Isuzugawa, K., Yamamoto, S., Chang, K. T., Gerton, G. L., and Imakawa, K. (2005). Effects of progranulin on blastocyst hatching and subsequent adhesion and outgrowth in the mouse. Biol Reprod 73, 434-42.
Gerton, G. L., Fan, X. J., Chittams, J., Sammel, M., Hummel, A., Strauss, J. F., and Barnhart, K. (2004). A serum proteomics approach to the diagnosis of ectopic pregnancy. Ann N Y Acad Sci 1022, 306-16.

Zhang, Z., Kostetskii, I., Moss, S. B., Jones, B. H., Ho, C., Wang, H., Kishida, T., Gerton, G. L., Radice, G. L., and Strauss, J. F., 3rd. (2004). Haploinsufficiency for the murine orthologue of Chlamydomonas PF20 disrupts spermatogenesis. Proc Natl Acad Sci U S A 101, 12946-51.

Kim, K. S., and Gerton, G. L. (2003). Differential release of soluble and matrix components: evidence for intermediate states of secretion during spontaneous acrosomal exocytosis in mouse sperm. Dev Biol 264, 141-52.