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:
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.
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.
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.
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.
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.
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.
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.
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.
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. 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, 2007.
Seeber, B., Sammel, M.D., Fan, X., Gerton, G.L.,
Shaunik, A., Chittams, J., and Barnhart, K.T. (2007). Panel
of markers can accurately predict endometriosis in a subset
of patients. Fertil Steril. Epub Aug 11.