Spermatogenesis involves two critical events: 1. The detachment of spermatogonial cell progenies from basal lamina and Sertoli cell anchoring sites upon commitment to meiosis. 2. The elimination of nonviable spermatogenic cell progenies to regulate the balanced differentiation of spermatogenic cells into sperm. These developmental events imply a continuous morphological reorganization of the seminiferous epithelium whose structural and molecular details are unknown. Our overall hypothesis is that these two events are interrelated and under control by three interactive signaling pathways: 1. The integrin beta1 subunit of the alpha3beta1/alpha6beta1 complex. 2. Members of the disintegrin protein family. 3. Caspase-3, an essential mediator in apoptosis. An analysis of the molecular events linking these pathways has never been attempted. One objective of this proposal is to understand how Sertoli cell geometry controls the anchorage and viability of spermatogonial cell progenies and the second is to determine how the oscillatory movements of spermatogonial cells gate the execution of induced cell death. Our overall hypothesis is that Sertoli cell stretching and contraction govern the differentiation of the spermatogonial cell progeny and its translocation into the adluminal compartment of the seminiferous epithelium. We plan to: 1. Test the hypothesis that Sertoli cell geometry and beta1 integrin regulate the anchorage of spermatogonial cells to Sertoli cell surfaces. 2. Test the hypothesis that selected disintegrins can either disrupt or stabilize spermatogonial-Sertoli cell adhesion. 3. Test the hypothesis that enhanced spermatogonial oscillatory cell movements following Fas ligand-induced apoptosis are a prelude to imminent cell death initiated by the fragmentation of actin and gelsolin activated by apoptosis caspase-3. The significance of the proposed studies is two-fold: 1. To our knowledge, this is the first attempt to link Sertoli cell geometrical changes to the life-and-death of the spermatogonial cell progeny. 2. In the long range, the discovery of ways to prevent and modulate spermatogonial cell death may have significant therapeutic and anticonceptive potentials in humans.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD036477-01A2
Application #
2852422
Study Section
Reproductive Biology Study Section (REB)
Program Officer
Rankin, Tracy L
Project Start
1999-04-15
Project End
2004-03-31
Budget Start
1999-04-15
Budget End
2000-03-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
City College of New York
Department
Anatomy/Cell Biology
Type
Other Domestic Higher Education
DUNS #
603503991
City
New York
State
NY
Country
United States
Zip Code
10031
Liska, Frantisek; Gosele, Claudia; Popova, Elena et al. (2013) Overexpression of full-length centrobin rescues limb malformation but not male fertility of the hypodactylous (hd) rats. PLoS One 8:e60859
Kierszenbaum, Abraham L; Rivkin, Eugene; Tres, Laura L et al. (2011) GMAP210 and IFT88 are present in the spermatid golgi apparatus and participate in the development of the acrosome-acroplaxome complex, head-tail coupling apparatus and tail. Dev Dyn 240:723-36
Kierszenbaum, Abraham L; Rivkin, Eugene; Tres, Laura L (2011) Cytoskeletal track selection during cargo transport in spermatids is relevant to male fertility. Spermatogenesis 1:221-230
Kierszenbaum, Abraham L; Rivkin, Eugene; Talmor-Cohen, Anat et al. (2009) Expression of full-length and truncated Fyn tyrosine kinase transcripts and encoded proteins during spermatogenesis and localization during acrosome biogenesis and fertilization. Mol Reprod Dev 76:832-43
Rivkin, Eugene; Kierszenbaum, Abraham L; Gil, Mara et al. (2009) Rnf19a, a ubiquitin protein ligase, and Psmc3, a component of the 26S proteasome, tether to the acrosome membranes and the head-tail coupling apparatus during rat spermatid development. Dev Dyn 238:1851-61
Kierszenbaum, Abraham L; Rivkin, Eugene; Tres, Laura L (2008) Expression of Fer testis (FerT) tyrosine kinase transcript variants and distribution sites of FerT during the development of the acrosome-acroplaxome-manchette complex in rat spermatids. Dev Dyn 237:3882-91
Kierszenbaum, Abraham L; Rosselot, Carolina; Rivkin, Eugene et al. (2006) Role of integrins, tetraspanins, and ADAM proteins during the development of apoptotic bodies by spermatogenic cells. Mol Reprod Dev 73:906-17
Tres, Laura L; Kierszenbaum, Abraham L (2005) The ADAM-integrin-tetraspanin complex in fetal and postnatal testicular cords. Birth Defects Res C Embryo Today 75:130-41
Tres, Laura L (2005) XY chromosomal bivalent: nucleolar attraction. Mol Reprod Dev 72:1-6
Kierszenbaum, Abraham L; Tres, Laura L (2004) The acrosome-acroplaxome-manchette complex and the shaping of the spermatid head. Arch Histol Cytol 67:271-84

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