Keynote Conference - Interevent

Symp#4 Cell Biology & Reproduction
Chair Luiz Renato França
Spermatogonial Stem Cell Niche in Vertebrates
Luiz R França
Luiz Renato França,Paulo HA Campos Júnior, Guilherme MJ Costa, Samyra SMSN Lacerda, Gleide F Avelar, Alana L Sousa,
*Marie-Claude Hofmann
Laboratory of Cellular Biology, Dept. of Morphology, ICB/UFMG, Belo Horizonte, MG, Brazil. *MD Anderson Cancer Center,
Dept. of Endocrine Neoplasia and Hormonal Disorders, Houston, TX, USA (email: lrfranca@icb.ufmg.br)
Spermatogonial stem cells (SSCs) are located in a particular environment called the “niche” that is controlled by the
basement membrane, key testis somatic cells, and factors originating from the vascular network. Although crucial for SSC
physiology, the niche is still poorly understood, particularly in non-model vertebrates where the testis cytoarchitecture
could provide important cues for niche components and regulation. Recently, we demonstrated that A und GFRA1 + cells
present preferential location (nearby blood vessels) in vertebrate species other than mouse and rat, such as zebrafish,
bullfrog, turtle and horse. Additionally, we observed that peccaries present a peculiar Leydig cell (LC) distribution,
whereby these cells situate around lobes of seminiferous tubules. Since the role of LCs as a niche component is not yet
clearly elucidated, this feature makes the peccary an interesting model for investigating the SSC niche. Subsequently, we
observed that in peccaries, ~93% of A undspermatogonia are GFRA1 + and that these cells are preferentially located adjacent
to the interstitium without LCs. Moreover, the expression of CSF-1 was observed in LCs and peritubular myoid cells (PMCs)
while its receptor was present in LCs and in GFRA1 + A und. In summary, besides reinforcing the fundamental role of Sertoli
cells in GDNF-GFRA1 signaling for SSC self-renewal in vertebrates, our data suggest that the mechanisms involved in SSC
physiology may be conserved in vertebrates. However, our peccary findings indicate that, contrary to PMCs, LCs might
play a minor role in the SSC niche/physiology and that LCs are probably involved in the differentiation of A und toward type
A1 spermatogonia.
Fetal Testis Differentiation and Function, its Regulation and its Disorders
Richard M Sharpe, Rod Mitchell, Afshan Dean, Karen Kilcoyne, Sophie Platts, Ashley Boyle, Sheila Macpherson, Chris
McKinnell, Richard Anderson, Sander van den Driesche
MRC Centre for Reproductive Health, The Queen’s Medical Research Institute, University of Edinburgh, UK (contact:
r.sharpe@ed.ac.uk)
Differentiation of the testis represents the first step along the pathway to becoming a male. Understanding of the
processes that regulate testis differentiation have added importance because there is increasing evidence that the
commonest disorders of human male reproductive health may largely stem form this period in life. Thus the testicular
dysgenesis syndrome (TDS) hypothesis proposes that subnormal ‘set-up’ of the fetal testis/cell types leads to subnormal
function (especially of the fetal Leydig cells) which, in turn, leads to male reproductive disorders that manifest at birth
(cryptorchidism, hypospadias, micropenis) or in adulthood (low sperm count, low-normal testosterone, testis germ cell
cancer). Direct evaluation of this hypothesis in humans is difficult, so we have used a rat model of TDS (fetal exposure to
dibutyl phthalate; DBP) to help elucidate key mechanisms and cell-cell relationships in the fetal testis, disruption of which
leads to TDS disorders. These have helped identify the masculinisation programming window (MPW) within which
testosterone production by fetal Leydig cells is critical for determining normality and ultimate adult size of all male
reproductive organs; deficiency in testosterone production in the MPW determines risk of later TDS disorders and can be
‘measured’ retrospectively by anogenital distance (AGD). Our studies show that DBP-induced focal dysgenesis
(malformation of seminiferous cords, intratubular Leydig cells, mis-specification of somatic cells) is closely interlinked with
deficiency in testosterone production in the MPW, even though the dysgenesis manifests after the MPW. The mechanisms
and factors involved, insofar as they are understood, will be discussed.
Antimicrobial Proteins Secreted by the Epididymis
Maria Christina W. Avellar
Section of Experimental Endocrinology, Department of Pharmacology, Universidade Federal de São Paulo – Escola Paulista
de Medicina (UNIFESP-EPM), São Paulo, SP, 04044-020, Brazil.
This presentation will focus on the expression and regulation of naturally occurring antimicrobial proteins secreted by the
epididymis. Aspects of the pattern of expression of mRNA and protein for selected genes, highlighting isoforms expressed
by the beta-defensin SPAG11B gene, in the adult tissue and during development of the rat epididymis will be discussed.
The effects of androgens, luminal fluid, glucocorticoids and exposure to in vivo bacterial products on their expression and
immunolocalization will be also presented. Financial Support: FAPESP, CNPq, CAPES and Fogarty International Center
(subcontract UNIFESP-EPM/University of North Carolina at Chapel Hill, USA). Email: avellar@unifesp.br.
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