Editing Sertoli cell (section)

==Function==
Because its main function is to nourish developing sperm cells through the stages of [[spermatogenesis]], the Sertoli cell has also been called the "mother" or "nurse" cell.<ref>{{cite journal | vauthors = Rato L, Alves MG, Socorro S, Duarte AI, Cavaco JE, Oliveira PF | title = Metabolic regulation is important for spermatogenesis | journal = Nature Reviews. Urology | volume = 9 | issue = 6 | pages = 330–8 | date = May 2012 | pmid = 22549313 | doi = 10.1038/nrurol.2012.77 | s2cid = 7385545 }}</ref> Sertoli cells also act as [[phagocyte]]s, consuming the residual cytoplasm during spermatogenesis. Translocation of cells from the basal lamina to the lumen of the seminiferous tubules occurs by conformational changes in the lateral margins of the Sertoli cells.

===Secretory===
Sertoli cells secrete the following substances:
* [[anti-Müllerian hormone]] (AMH), secreted during the early stages of [[fetus|fetal]] life
* [[inhibin]] and [[activin]]s, secreted after puberty, work together to regulate [[Follicle-stimulating hormone|FSH]] secretion
* [[androgen-binding protein]] (also called testosterone-binding globulin) increases testosterone concentration in the seminiferous tubules to lightly stimulate spermatogenesis
* [[estradiol]] - an [[aromatase]] converts [[testosterone]] to 1,7-beta-estradiol to direct [[spermatogenesis]]
* [[ERM transcription factor|ETS Related Molecule or ERM transcription factor]] is needed for maintenance of the [[spermatogonial stem cell]]s in the adult testis
* [[transferrin]], a blood plasma protein for iron ion delivery<ref>{{cite journal | vauthors = Xiong X, Wang A, Liu G, Liu H, Wang C, Xia T, Chen X, Yang K | title = Effects of p,p'-dichlorodiphenyldichloroethylene on the expressions of transferrin and androgen-binding protein in rat Sertoli cells | journal = Environmental Research | volume = 101 | issue = 3 | pages = 334–9 | date = July 2006 | pmid = 16380112 | doi = 10.1016/j.envres.2005.11.003 | bibcode = 2006ER....101..334X }}</ref>
* testicular ceruloplasmin, a [[ceruloplasmin]]-like protein which is immunologically similar to serum ceruloplasmin.<ref>{{cite journal | vauthors = Skinner MK, Griswold MD | title = Sertoli cells synthesize and secrete a ceruloplasmin-like protein | journal = Biology of Reproduction | volume = 28 | issue = 5 | pages = 1225–1229 | date = June 1983 | pmid = 6871315 | doi = 10.1095/biolreprod28.5.1225 | doi-access = free }}</ref>

===Structural===
The [[occluding junction]]s of Sertoli cells form the [[blood–testis barrier]], a structure that partitions the interstitial [[blood]] compartment of the testis from the adluminal compartment of the seminiferous tubules. Because of the [[apical (anatomy)|apical]] progression of the [[spermatogonia]], the occluding junctions must be dynamically reformed and broken to allow the immunoidentical spermatogonia to cross through the blood-testis barrier so that they can become immunologically unique. Sertoli cells control the entry and exit of [[nutrient]]s, [[hormone]]s, and other chemicals into the tubules of the testis as well as make the adluminal compartment an immune-privileged site.

Sertoli cells are also responsible for establishing and maintaining the [[spermatogonial stem cell]] niche, which ensures the renewal of stem cells and the differentiation of [[Spermatogonium|spermatogonia]] into mature germ cells that progress stepwise through the long process of spermatogenesis, ending in the release of [[Spermatozoon|spermatozoa]] in a process known as [[Spermiogenesis|spermiation]].<ref>{{cite journal | vauthors = O'Donnell L, Nicholls PK, O'Bryan MK, McLachlan RI, Stanton PG | title = Spermiation: The process of sperm release | journal = Spermatogenesis | volume = 1 | issue = 1 | pages = 14–35 | date = January 2011 | pmid = 21866274 | pmc = 3158646 | doi = 10.4161/spmg.1.1.14525 }}</ref> Sertoli cells bind to spermatogonial cells via [[N-cadherin]]s and [[galactosyltransferase]] (via carbohydrate residues).

===Other functions===
During spermatogenesis, Sertoli cells provide nutrition to the spermatogonia.

Sertoli cells are capable of repairing [[DNA damage (naturally occurring)|DNA damage]].<ref name="pmid19164176">{{cite journal | vauthors = Ahmed EA, Barten-van Rijbroek AD, Kal HB, Sadri-Ardekani H, Mizrak SC, van Pelt AM, de Rooij DG | title = Proliferative activity in vitro and DNA repair indicate that adult mouse and human Sertoli cells are not terminally differentiated, quiescent cells | journal = Biology of Reproduction | volume = 80 | issue = 6 | pages = 1084–91 | date = June 2009 | pmid = 19164176 | doi = 10.1095/biolreprod.108.071662 | doi-access = free }}</ref> This repair likely employs the process of [[non-homologous end joining]] involving [[XRCC1]] and [[PARP1]] proteins that are expressed in Sertoli cells.<ref name="pmid19164176"/>

Sertoli cells have a higher mutation frequency than [[Spermatogenesis|spermatogenic cells]].<ref name="pmid9707592">{{cite journal | vauthors = Walter CA, Intano GW, McCarrey JR, McMahan CA, Walter RB | title = Mutation frequency declines during spermatogenesis in young mice but increases in old mice | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 17 | pages = 10015–9 | date = August 1998 | pmid = 9707592 | pmc = 21453 | doi = 10.1073/pnas.95.17.10015 | bibcode = 1998PNAS...9510015W | doi-access = free }}</ref> Compared to [[spermatocyte]]s, the mutation frequency is about 5 to 10-fold higher in Sertoli cells. This may reflect the need for greater efficiency of DNA repair and mutation avoidance in the germ line than in somatic cells.

=== Immunomodulatory properties of Sertoli cells ===
Besides expressing factors that are crucial for sperm cell maturation, Sertoli cells also produce a wide range of molecules (either on their surface or soluble) that are able to modify the immune system. The ability of Sertoli cells to change the immune response in the tubule is needed for successful sperm cell maturation. Sperm cells express neo-epitopes on their surface as they progress through different stages of maturation, which can trigger a strong immune response if placed in a different part of the body.

==== Molecules produced by Sertoli cells associated with immunosuppression or immunoregulation ====
[[FAS/FAS-L]] system – expression of Fas ligand (Fas-L) on the surface of SCs activates apoptotic death of Fas receptor-bearing cells, e.g. cytotoxic [[T cell]]s.<ref>{{cite journal | vauthors = Dal Secco V, Riccioli A, Padula F, Ziparo E, Filippini A | title = Mouse Sertoli cells display phenotypical and functional traits of antigen-presenting cells in response to interferon gamma | journal = Biology of Reproduction | volume = 78 | issue = 2 | pages = 234–42 | date = February 2008 | pmid = 17989360 | doi = 10.1095/biolreprod.107.063578 | doi-access = free }}</ref>

- soluble FasL: increasing the effectivity of the system

- soluble Fas: FasL blockage on the surface of other cells (no apoptotic induction in Sertoli cells by immune cells)

B7/H1 – decreasing proliferation of effector T-cells<ref>{{cite journal | vauthors = Kaur G, Thompson LA, Dufour JM | title = Sertoli cells--immunological sentinels of spermatogenesis | journal = Seminars in Cell & Developmental Biology | volume = 30 | pages = 36–44 | date = June 2014 | pmid = 24603046 | pmc = 4043859 | doi = 10.1016/j.semcdb.2014.02.011 }}</ref>

Jagged1 (JAG1) – induction of Foxp3 transcription factor expression in naive [[T cell|T lymphocytes]] (increasing relative numbers of [[Regulatory T cell|T regulatory cells]])<ref>{{cite journal | vauthors = Campese AF, Grazioli P, de Cesaris P, Riccioli A, Bellavia D, Pelullo M, Padula F, Noce C, Verkhovskaia S, Filippini A, Latella G, Screpanti I, Ziparo E, Starace D | title = Mouse Sertoli cells sustain de novo generation of regulatory T cells by triggering the notch pathway through soluble JAGGED1 | journal = Biology of Reproduction | volume = 90 | issue = 3 | pages = 53 | date = March 2014 | pmid = 24478388 | doi = 10.1095/biolreprod.113.113803 | doi-access = free }}</ref>

[[Protease inhibitor (biology)|Protease inhibitor-9]] (PI-9) – member of serpin family (serine protease inhibitors),<ref>{{cite journal | vauthors = Potempa J, Korzus E, Travis J | title = The serpin superfamily of proteinase inhibitors: structure, function, and regulation | journal = The Journal of Biological Chemistry | volume = 269 | issue = 23 | pages = 15957–60 | date = June 1994 | doi = 10.1016/S0021-9258(17)33954-6 | pmid = 8206889 | doi-access = free }}</ref> which induces secretion of protease [[Granzyme B]], cytotoxic T-cells and NK cells are able to induce apoptosis in target cell. SCs produce PI-9 that irreversibly bonds Granzyme B and inhibits its activity.

[[CD59 antigen|CD59]], a surface molecule on SCs and a member of the [[complement regulatory protein]]s (CRP), inhibits the last step of the [[Complement system|complement cascade]], the formation of the [[Complement membrane attack complex|membrane attack complex]].<ref name=":1">{{cite journal | vauthors = Lee HM, Oh BC, Lim DP, Lee DS, Lim HG, Park CS, Lee JR | title = Mechanism of humoral and cellular immune modulation provided by porcine sertoli cells | journal = Journal of Korean Medical Science | volume = 23 | issue = 3 | pages = 514–20 | date = June 2008 | pmid = 18583891 | pmc = 2526533 | doi = 10.3346/jkms.2008.23.3.514 }}</ref>

Clusterin, a soluble molecule with functions similar to CD59, forms a complex with Granzyme B and inhibits activation of apoptosis by T-lymphocytes or NK cells.<ref name=":1" />

[[TGF beta signaling pathway|TGF]]-beta, a transforming growth factor beta (its direct production by SCs is controversial), contributes to the induction of regulatory T-cells on the periphery.<ref>{{cite journal | vauthors = Iliadou PK, Tsametis C, Kaprara A, Papadimas I, Goulis DG | title = The Sertoli cell: Novel clinical potentiality | journal = Hormones | volume = 14 | issue = 4 | pages = 504–14 | date = October 2015 | pmid = 26859601 | doi = 10.14310/horm.2002.1648 | doi-access = free }}</ref>

==== Other molecules ====
[[CD40 (protein)|CD40]], a molecule associated with [[dendritic cell]]s (DCs). SCs are able to down regulate the expression of CD40 on the surface of DCs, by an unknown mechanism. Downregulation of CD40 results in the decreased ability of DCs to stimulate the T-cell response.<ref name=":1" />

Sertoli cells are also able to inhibit the migration of immune cells by lowering immune cell infiltration to the site of inflammation.