1. The Sertoli Cell Junction
Dynamics
Falana, Benedict Abiola
Department of Anatomy,
CMUL.
Matriculation Number: 109091016
ANA 902
25th February 2014
1

2. OUTLINE
• INTRODUCTION
• LITERATURE REVIEW
• DISCUSSION
–Sertoli cell structure
–Sertoli cell function
–Sertoli cell JUNCTIONS
• CONCLUSION
• REFERENCES
2

3. INTRODUCTION: List of Abbreviations
 BM= Basement Membrane
 ECM= Extracellular Matrix
 BTB= Blood-Testis Barrier
 TJs= Tight Junctions
 ES= Ectoplasmic
Specializations
 NAMPC= Nectin-Afadin
Multi Protein Complex
 ILMPC=Integrin-Laminin
Multi Protein Complex
 TT= Testosterone
 FSH= Follicle Stimulating
Hormone
 GDNF= Glial cell line
Derived Neutrotrophic
Factor
 CCMPC= Cadherin-Catenin
Multiprotein Complex
 IPEC-J2= Intestinal
Epithelial cells
 CAM= Cell dhesion
Molecule
 AC= Adenylate Cyclase
 MDCK= Mardin Darby Canine
Kidney
 CLASP= Cytoplasmic Linker
Associated Protein
 PI-3= Phosphatydyl Inosotol
 PLA2=Phospholipase A2,
 cAMP=Cyclic Adenosine
Monophosphate
 RHOB= Ras Homolgue B
 PKA= Protein Kinase A
 MAP Kinase= Mitogen Activated
Protein Kinase
 FGF- Fibroblast Growth Factor
 ICAM= Intercellular Adhesion
Molecule
 ST- Seminiferous Tubule
 FAK- Focal Adhesion kinase

4.  NOS= Nitic Oxide Synthase
 CATNB= Beta Catenin B
 GJ= Gap Junction
 AJ= Adherens Junction
 AnJ= Anchoring Junctions
 CAM I = Calmodulin I
 NR5A1= Nuclear receptor
steroidogenic factor
 RAI 14- Retinoic acid
inducible protein 14
 ZO- Zona Occludens
 CX43- Connexin 43
 SRY- Sperm Region Y
 TRAF4=TNF receptor associated factor
 TM3= Transmembrane Segment 3
 ILK= Integrin Linked Kinase
 ERM= Ezrin Radixin & Moesin
 GDNF=Glial Cell Line Derived
Neurotrophic Factor
 MIS=Mullerian inhibitory Substance
 JAM= Junction Adhesion Molecule
 TGFβ= Transforming Growth Factor
Beta
 ERK= Extracellular signal Regulated
Kinases
 ECL2= Extracellular loop 2
 TNF= Tumor zNecrotic Factor
 SOX= SRY-related HMG Box
 GATA=Globin Transcription Factor

5. Introduction: SPERMATOGENESIS
• 1. Spermatogonia
– Proliferate by mitotic divisions
to provide stem cells & cells
which will proceed through
spermatogenesis (1º
spermatocytes)
• 2. Spermatocyte
– diploid cells (2n) give rise to haploid
cells (1n)
– 1º spermatocytes enter Meiosis
I to form 2º spermatocytes
which then enter Meiosis II and
result in spermatids
• 3. Spermatids
– spermatid differentiation into
spermatazoa
5

6. INTRODUCTION
 Enrico Sertoli
(University of Pavia Italy 1865)
 1862; discovered Sertoli cell
Published in 1865
6

7. Enrico Sertoli (1842 – 1910)

8. Questions
• What is the mechanism of by which
developing germ cell traverse the
epithelium?
• What signalling event determine the time of
for germ cell to translocate from one site to
the other?
• What interactions between Sertoli and germ
cells take place during translocation?
• What are the events leading to formation
and disruption of Sertoli-germ cell
junctions?

9. Ultrastructure of the Sertoli Cell: Irregular nuceli, Mitochondria, lipid and RER are prominent.
Courtesy : www.naturescience.com
• Ultrastructure of the Sertoli Cell: Irregular
nuceli, Mitochondria, lipid and RER are
prominent

10. LITERATURE REVIEW
On going Controversies.
• A Single Spermatogoonium (2n)
gives rise to Eight Spermatids (1n)
(de Krester & Kerr 1988).
• Preleptotene and Leptotene
spermatocytes. (Zipper Theory)
• BTB.
(Byers 1993; Pelletier 2001).

11. • Sertoli-Germ cell bi-directional
secretion of Androgen-binding
protein. (Gunsalus & Bardin 1980).
11

12. Table 2: Proteins Secreted by Sertoli Cells
• a Table modified from Griswold, 1988.
Hormones or Growth Factors
TGF- precursor
Anti-Muillerian hormone (MIS)
Inhibin
TGF-
EGF-like growth factor
Basic FGF-like growth factor
Seminiferous growth factor
IGF-1
Interleukin-l-like factor
Leydig cell stimulatory factor
Basement Membrane Components
Type IV collagen
Laminin
Enzymes
Procathepsin L (cyclic protein 2)
Plasminogen activator
Transport proteins
Androgen-binding protein
Transferrin
Ceruloplasmin
Other
Sulfated glycoprotein 1 (prosaposin)
Sulfated glycoprotein 2 (clusterin)
Testibumin
Testins

13. TABLE 1: Germ Cell-Sertoli Cell
Effects on Germ Cells Effects on Sertoli Cells
 Limited differentiation in co-cultures
  DNA and RNA synthesis
  Protein synthesis
  Viability and ATP levels
  Adenylate cyclase activity
  Protein phosphorylation
 Alterations in glycoprotein composition
 Alterations in membrane proteins
  Transferrin secretion
  ABP secretion
  Estradiol secretion
 Cyclic variations in secretory products

14. Reglation of Spermatogenesis
FSH.
LH.
TT.
ABP.
(McLachlan et al., 2002 ; Kerr et al. 2006; ).
SRY
SOX
HMG
FGF
GATA
FOG
GADD 45g
NRSA1
(Hiramatsu 2010; Pask 2010; Bormann 2011;
Johnen 2013)
14

15. • CX43 alters Occludin expression in the rat ST.
(Gerber 2014)
• Spectrin and Plectin sorrounds the actin cuffs
of apical tubulolobular complexes in the rat.
(Aristaeuss de Asis 2013)

16. • Clathrin/actin-base endocytic
machinery is associated with
junction turnover in ST.
(Vogl 2014).
• Dicer is required for sertoli cell
function and survival.
(Papaioannou 2009; Kim 2010;Hensley et al., 2014).
16

17. • RIA 14 regulates F-actin dynamics
at the ES.
(Qian 2013).
• CAM-I enhances Germ-Sertoli cell
interaction in spermatogenesis.
(Lewis 2005; Wakayama & Iseki 2009)
17

18. • FAK is a regulator of F-actin
dynamics (Li 2013)
• Disruption of Sertoli-germ cell
adhesion function limited to
adherens junctions.
(Xia et al., 2005)
18

19. • Taurine disrupts the morphology and
Ultrastructure in the testis of mice.
(Abdel-Moneim 2013)
• TGF-beta3 regulates anchoring junction
dynamics via the Ras/ERK signaling
pathway.
(Xia 2005)
19

20. • Ultrastructural changes of the
Sertoli and Leydig Cells following
STZ induced diabetes.
~ Body Weight ↓ (P˂0.05)
~ Testicular Weight↓(P˂0.05) in
diabetic rats compared with
controls.
(Kianifard 2012)

21. • Β- Conglycinin reduces the tight
junction occludin and ZO-I
expression in IPEC-J2.
(Brosnan 2012 ; Zhao et al., 2014)
21

22. • Palmitoy-protein thioesterase I
(PPTI) an obesity induced testicular
marker of reduced fertility. (Liu 2014)

23. • Claudin-3 and Claudin-5 folding
and assembly into tight junctions
are controlled by non- conserved
residues in TM3 and ECL2
segments.
(Rossa et al., 2014; Shabazi 2014).
23

24. • Immunohistochemical analysis of
Histone H3 modifications in germ
cells during mouse
spermatogenesis.
(Song et al., 2011).
24

25. • TRAF4 impedes the formation of
tight junction integrin-linked
kinase (ILK) Talin-1.
(Rosseau et al., 2014).
25

26. DISCUSSION
STRUCTURE
Blood-testis barrier
Controls the entry and exit of
nutrients hormones and other
chemicals into the tubules
 Makes the ad luminal part of ST, an
immune privileged site.
(Wakayama 2009; Kopera 2010)
26

27. SECRETION:
MIS
 Inhibin
 Activin
 ABP
 Estradiol aromatase. 27

28. GDNF
ERM
Transferrin
(Xiong et al., 2006)
28

29. Hormones,
Growth factors,
Proteases
(Catepsins,Metzincin,Plasminogens)
Protease inhibitors
Components of the extracellular
matrix
29

30. Junctions
The BTB
Tight junctions(TJs)
 Ectoplasmic specializations (BES)
Tubulolobular complex (BTC)
 Desmosome-like junctions
Hemidesmosomes
30

31. Blood Testis Barrier- endocrine reviews
31

32. BTB
FUNCTIONS
Allow sertoli cells to control the
ad- luminal compartment.
Regulates the chemical
composition of luminal fluid.
Sensitive to trauma and
Autoimmune response 32

33. TJs
COMPOSITION:
Fused membranes
Bead-like Components
Span adjacent membrane
Formed by strands of
transmembrane proteins .
33

34. TJs
FUNCTIONS
Barrier Function
Impermeable
Regulates absorption
Creates a seal
34

35. AJs
• Zona adherens
• Located at site of cell-cell interaction
• Actin-linked
• Attaches ECM
• Posses specific transmembrane
receptors of the integrin family
• Adhesive function

36. Cadherin
 Ca ion dependent CAM
adhesion at adherens junction

37. Role:
Teetheres cells to the ECM.
Tranduce signals.
Proliferation.
Migration .
Differentiation .

38. AnJ
• Desmosome-like junctions
• Ectoplasmic specializations

39. Key
• 1.Peritubular cells
2. Basal membrane
3.Spermatogonia
4. Tight junction
5. Spermatocyte1
6. Spermatocyte2
7a. spermatid
7b. Spermatid
8. Acrosome
9. residual bodies
10.Sperm cells
11. Nucleus of sertoli cell
A. Basal zone
B. Adlumunal zone
• www.instantanatomy.com.
39

40. Desmosome-like Junctions
COMPOSITION
Macula adherens
Found between Sertoli cells at the
BTB
Germ cells up to but not including
step 8 spermatids.
(Holthofer et al.,2007).
40

41. Desmosome-like junctions
• COMPOSITION
 Desmoglea.
 Dense Cytoplasmic plaques.
(Garrod et al., 2005; Holthofer et al., 2007; Scothern & Garrod 2008)
41

42. Desmosome-like junctions
COMPOSITION:
 Cadherin family
(a) Desmogleins (Dsg)
(b) Desmocolins (Dsc) © Integrins
Associated with keratin & Vinculin
Distinct at molecular level
Calcium ion dependent (CAM)
Sites of signal transduction
(Bruce et al., 2000)
42

43. Desmosome-like Junctions
• FUNCTIONS
~Mediate cell adhesion ( Delva et al.. 2007)
43

44. Desmosome-like junctions
FUNCTIONS:
 Cell adhesion
 Cell proliferation,
 Cell differentiation,
 Cell migration and
 Morphogenesis.
(Garrod & Chidley 2004)
44

45. ES
CCMPC
CATENIN ( α-β-ϒ-) :
Cytoplasmic proteins
Bind to the C-terminus of the type I/II and
desmosomal cadherins
Regulates cadherin-mediated adhesion via
the actin and intermediate filament
cytoskeletons
( Das et al., 2014)
45

46. ES
CCMPC
(Wine & Capin 1999;Johnson & Boekelheide 2002; Lee et al., 2003, 2004; Yan et
al., 2008a; Delva & Kowalczyk 2009; Yan et al., ; 2008b; Izumi et al., 2006).
• Best studied actin-based adhesion
unit.
46

47. Regulates:
Cytoskeleton
Cell polarity,
Control of cell division and
Tumor suppression
• ( 5 distinct subfamilies, type 1 and 2,
desmosomal, atypical, and cadherin-
like)
47

48. ES
NAMPC
 Nectins (1-5)
 Nectin-like molecules (
Necls, Necls1-5)
--Ca++-independent
--immunoglobulin-like moles.
48

49. ES
Role:
 Adhesion
 Proliferation
 Differentiation
 Survival
 Migration
 Cell polarity.
( Takai & Natkanishi 2003; Takai et al., 2003, 2008c; Irie et al., 2004)
49

50. ES
ILMPC
Functions
• Connects a cell to ECM
(Margadant et al., 2008; Geiger et al., 2009)
• Constituents of the BM
(Miner & Yurchenco 2004; Miner 2008)
50

52. SUMMARY
• The integrity of the BTB cannot be
compromised.
• TJ on and off switch
• Signal transduction is very essential and
crucial in tight junctional dynamics.
52

53. CONCLUSION
• Changes in secretory activity of either Sertoli
or germ cells initially take place at the level
of cell junctions.
• Biology of desmosome-like junctions and ES
needs to be thoroughly investigated.
• Basis of male contraception and infertility
treatment.
53

54. Acknowledgement
• Sincere gratitude to my able supervisors
Dr. Francis Duru and Dr. Abraham Osinubi for their
mentorship role.
• I also want to appreciate my Teachers Dr.
Ibeabuchi, Dr. Oremosu, Dr. Kusemiju, Dr.
Dosumu, Dr. Olabiyi, Dr. Gbotolorun , Dr. Yama for
their assistance during preparation for the review.
• A big thanks to fellow Postgraduate students and the
non-teaching staff of the Department.
54

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