AGENCY FOR INTERNATIONAL DEVELOPMENT PPC/CDIE/01 REPORT PROCESSING FORM DiTER 1:-iFORMATIO:>i 0:-il Y IF :-iOT 1:-iCllJDED 0:-i COVER OR TITLE PAGE Of DOCDIE:-iT 3. Publka.tion Dalr I ::>oo3 4. Documt'nt Titleffranslated Title Sertoli Cell Ttght Junction Dynamics: Their RegulatiOn During Spermatogentsts 5. Author (s) I. Wing-Yee Liu 2. Dolores Mruk 3. Will Lee 4. C. Yan Cheng rContributing 0.-gani.ation (s) 7. Pagination 8. Report ~umber 9. Sponsoring A.I.D. Office I I I Office of Population and Reproducti,·e Health 10. Abstract (optional- 250 word limit) Biology of Reproduction (68) pp. 1087-1097. J 1. Subject Ke~~-ords (optional) 6 12. Supplementan· :'iotes SO I To expand the range and optimize the use and availability of safe. effecti,·e and acceptable technologies for the prevention of pregnancy and STis HI\". 13. Submitting Official 14. Telephont ~um~l'" 15. Toda~··s Dare Ruth Cooeland !4131 586-7977 Seotember 30. ::>001 DO :'\OT wnte hciO\~ th1s lmc 16. DOCID 17. Document Disposition DOCRD I I e<\ II Dl"PUC\ TE I I AID 590-7 (10188) I BIOLOCiY OF REPRODlTTIO'\ 68. 10X~-1nq- 1 ~~~~~-~~ PubJi,hcJ nnlinc hcf11rt: print_-:; l O..:!l1her ~!HI,:: DO\ 10.1 OY5;btlllr<.?pwJ.l !12.!11 !l_~-1 Mini review Sertoli Cell Tight Junction Dynamics: Their Regulation During Spermatogenesis' Wing-Yee lui,' Dolores Mruk,' Will M lee,' and C. Yan Cheng'·' Population Council. Center (or Riomedical Re_q\Jrch. \C\\ )orJ... \c\t )nr~ f(l0_1 l Departrncnt of ZoologL _, Thf' L ·ni\ cr~it\ o( Hong l<onL;. HnnL; f..un~. Chin,1 ABSTRACT carl~ ... rage 1.\ 1.~1. It I'- ,,:(ln,:-.·1\.tflk that th1" '-'\Cnt tlf ~~.:rm L·e!l flH)\emcnt ;t~..·r~"'" tht.' '-l'lllllllfi..'fi'L~'- C~'ithchum llunn:-: During spermatogenesis, developing preleptotene and lep­ totene spermatocytes must translocate from the basal to the ad­ "rcrmatn~crk'"i" in the te"t'' 1" .1""'"--'-ttcJ \\ith c\tcrl'-1\;..· luminal compartment of the seminiferous epithelium so that ful­ rc,!m~o.·!llrint:' tlf t!t:'ht iun,:lttlll~ •TJ,,. ,:ell-,:-.·11 .t..:t;n-fl.t,-.·..__1 ly developed spermatids (spermatozoal can be released to thP adhereJb ,iuTk·tiPn" 1.-\J" '· .Hlll ,:cll-,:cll :ntcrnl<..·di,ttt· n!,t­ tubular lumen at spermiation. It is conceivable that the opening mcnt-h;t,L·d Lk.,lllt"-t'llle-I!J....c _iun,:tl<'rl" Y;.·t :tl\..· '"'j,l]~~;~ .IIlli and closing of the inter-Sertoli tight junctions (T)sl that consti­ r'--·gu!atitHl 111 ...·,·]! Jlllh..'tltll1 re,trth:tunn_; rcm.t!n l.tr:=cl~ .1 tute the blood-testis barrier are regulatPd by an array of intrigu­ 111~ -..!LT} IP rcrn}JLJL'ti\ l' rh: '-lll]t•fl'-t" ingly coordinated signaling pathways and molecules. Several H~t..,ed 1111 the re,u]t, ,,( "!ullH.> ,_-~ln,Ju,:l;..'d \\lll: 11th,.'r -...'t'­ molecules have been shown to regulate Sertoli cell TJ dvnamics; ithc!i;t P\er the pa"t de,_-.~dc. '--Lk·h ,('- \Lliln-D.irh_:. C.ult!l;..' they include, for example, transforming grmo, th factor 133 1\.idne~ 1\IDCI\.t •.:ell" dfld J....cr.ttm,..,:;.t._·,_ rl I'- Jn,:r-.'.t'-In_;l~ (TGFJBl, occludin, protein kinase A, protPin kinase (, and sig­ ~.:lc~tr th,tt ,iun ..:ti,,n d: n.1111i,_·, .tr ..· r ...·~uLt ...·li l .. tr_::cl_:. b_:. TJ­ naling pathwa\o·s such as the TGFj33/p38 mitogen-activated pro­ intcgral memhr,lfk' rr• 1tl'ill'-. d!lll ~: tlk'lf .1'-"t\o,:l.:tl'd '-l~n.d­ tein kinase pathway. Yet the mechanisms that regulate these in~ moleL·uk'" ~~~ th._· .Jllfl...'l!llfl \l~t prt•k'tll ;~th"'f,t:~.~r~L~:~~·n events are essentiallv not known. This minirPview summarizes deph~."-phnr:Ltti\lll 1f~.,r fl'\1;..'\~'- ,;_:._· "·'I'! \lth•'u:;:h TJ some of the recent .ldvances in the stud"· of TJ dvnamics in the '-lflll'ture" in the "emilllfl'rllu" LTHhc!Jum 1"-"'"e"" '-1 1 1lll' fc.t· testis and reviews several models that can be used to stud"· TJ turc" uniqut· tn thL· IL'"ti". the_:. .tre "irmLtr l1' th''"'" f,'lllllltn dynamics. It also highlights specific areas for future research nther '--·pith'--·lia t for i"L'\ it'\\"· "'--''-' I. ' - · -\, ,u,·h. It h.t" toward understanding the precise phvsiological relationship be­ hcen po.,tubted th;ll _iunl'litlfl ll~ n.tmi,_-, 1n the '-l'tninifcr~'L~'­ tween junction dynamics and spermatogenesis. cpithclium <trl' l'L'~ubteJ h~ me,·h.t!ll'-!11'- '-lmd.tr !1' rh~"''-' 1r1 Sertoli cells. si~naf transrluctrnn. SfJerrna!n!;t'!H'.~h re~~~-~ other L'pithclia l-L :'i. It'" Jr(lllh.: th.~t th._, '-Lil..l~ 1'! IUrh:t!l'rl d!nami~,.·.., in tilL· tc"t~'- j, a f,,nmd.tbh: r.~'k. l.ir_::- ..·1~ h~x.w ... '-· INTRODUCTION nf the ~,.·pmple\it_:. ,,f "pcrm.ttl'~'''ll''-l". \~hr ..:h l'- Irl!n_::-uin_;!~ ret:'ulated h! different Jlhllc,_:u!,·, .tn,._! p.ttll\~.~~" .tt th'--' ,._·"·1- .-\single ... permatogonium (diploid. ~nl \\ill gi\c ri"e to !ular. hiochcmi~..·al. .tlld m,,]c,_·uLtr k\ ._,], -\],_,,_ the,-.· r~·:;:u­ eight ..:,pcrmatid:-. ! haploid. In l Juring ... pamatngeJlL'"i" ~ fnr latnr~ e\l'llb lll,.,c\~ ~,"--,.:ur "-,lJldJIT;_'!'lt1;- 1n !h;..' "'-'!1ltntL.. ·r~'Lh re\·ie\\ "· -.ce I I. =:I l. At the ... ame time. Jc\·c[nping prekp­ epithelnun at L'a,_·h '-Ltfl' 11f rhe ...:~ "-]...> totcne and leptotene .,pcrmatoc! tc ... that diff'--·rcntiateJ fnHll -\l!hnu~h the "tnh:IUre .11hl fu;:,::!•'l: ,q [he S;._·n~'lt "·ell typc B "pamatngonia hchinJ thc hlo()J-tc,ti., harri'--'r t BTB 1 TJ that l'Prl'-titutL'" the BTB :n the tc<:~ h.t\;__' tx·t"c rC\k'\\,_.,_J at tht' ha .... al L·ompartment of the "cminif'--·rnu., epithelium ! "'--'t' I~- -]1. the 1111 •kdik ....Hld p.tlt1\\ .. 1: .... th.tl rc:_:u l.ttc TJ mu ... r tra\('f-.,e the BTB and 1110\'--' into the aJiumuul cnm­ J\narni •.> in the ll''-tl" h,t\l' rcm,tu1c ... l !,tr:;;._·[~ ,_,r.,,_·ur.__· .ult!l partment for further de\ elopment t fl)f rc\ ie\\ "· "cc 11. 3- reL'\.."illl_:.. Thi" milllfl'\ It'\~ rr-.·,enh the r ...· ... uit' ,,( f;._',.:,·nt rin,_I­ 7]1 !fig. l ). \\hich take ... pi;Ke at late ... tagt' \'Ill thwugh Jng" Ill thi" :tft':t. ~llld in r.tnJ..:UI.tL !he ,:UfT;_'nl '-[,:[U' • 1 :· th,_· rc,cardl. Funhcrnhlrt·. \\;__' .tttL'fll!'l'-~Ll !1' h1:::hll_;ht "i"'-'"·ItJ ...· Th•, ·.•,rJr, '.'.,b •c,pour~t>d :n 1ur: h-, ':1!' (-(J'\,R_-\[) f',,·.;r.l''' ( :Z ( f\ .;'.H1'-. I-IC-'•h-t11-\.J:'c:{IC-t'1--...'t••{ 'I( .w--:lil.-'·---1-·,,[)\\ , __ .,,, re"e~trdl ,tfL'.t'- th,tt Lfc,Cf\ e ;~!lcnth'r: ;n fuwre '-HILltc-" Th'--· minirc\il'\\ j, nnt Jntcndc~I 111 lx- ::\h.:Lbli\C. r.:tha. H 1... me~tn! [11 "'--'f\C ;1" .1 t:'liide f,,r futurL' '-lllllic" Rc.td~.·r, .tft' '1<1:11 >!"1.1! ~)e\ e!npn'f'n~ '"~')' f jR"-.- -\-1 ,, ;_.,,._, 111, ·r,,, ;,;rJ''' :>· . • ,,,_ ...._,," ,_ "tnm~l~ cncnur.t~cd il' ft'.tli C.1rlicr J't'\ J;_'\\" • ... ._• ._. ~-t- -I 1 [,, :1"!•<- F•>U''(~,1tH>" ~1-, •ht• HtlPC: h.••r'·.; Rt·~t·.-t'< "{.r_:n· ( .,.__,.,, fl"-l_ -1·•~ gain a mnrc L-nmprchen'-1\ c \ il'\\ \'f thi' ri ..·i-.1 1.ll\\ :(J\\.\\.1. ,J'1C: C.~.( \\_1 L '-'-.1~ ,,;p(l<>''•·•: ;'' py· :•·. ,1 :·,,,_•.;•,Jc .Jatr· 't''l',H' h '\ h, l;d·,n;:l .~'.\drd rr• •!1' :"•· l "·, ,-·~-". · t !. ,r•.: f.-,···~ lti"(''IV•'ld,•ntt"· c· 1.1n c·''P~',.; f',,n_JI,l',,n ( .. __ .. , !..'i;l), ., -\·.•-"~ FUNCTIONS OF THE TJ A'D THE CLJRRE' T THEOR' - 'v-,·. l1•r-,_ '\.l ;,1," F-\\ ..:' ...' ;; ··-"'J, .• , .. :"'f'·' OF TJ REGULATIO' "THE TESTIS 'Ill~··,-(· !1 ''.l'dcj Functinn~ nr ihe TtL;h: /;__;:'t .''r)" Rt•( t·;\ r·cf· 1~ -\u;__;u-.t ...'llll...' Ti~ht _iunL'lll'll'- afL' the ~~nl;. J....rh'\" n '':"·luJul~ _JU!ldl\lll F":r•: di•(, •1:1. ~,1 -\uQLH _'tl(l_' h~thc!u. !~.,. \c c'i·p:t•c! )11 Oc :()ber ..'lll\2 t! pe ... in mammalian epithcl!.t .111Ll en ... The_:. .trc L''-ltl'J at thl' 111\h[ .tpicil f('~\tlf1 tlf crnh:l!.t .tnd erh.Jil!hcli,t. the! .,cal intL~rL·elluLtr ,r,t..:'-'"· ;Hll! "-,,mnt~ut:: :,, the ~~·r- 1088 Tight junction Seminiferous tubular lumen Sertoli cell Adluminal compartment sc sc • ' ' Tight junctions Adherens junctions Sertoli cell Basal Desmosome-like junctions ·•• ~ compartment Ectoplasmic specializations, api~:~-.~-~ ••• J 0 0 0 Ectoplasmic specializations, basal ·•••·· •.. •···· Basement membrane J ·············· - --o- -<r--{l--- .--fY.-- . Collagen fibril network Basal lamina Hemidesmosomes ........................... -----· .• _. .. · 'Myoid cells/fibroblasts FIG. 1. A diagramm.Jtic drawing that illustr.Jte'> thl• cu1W11l tight junction c,t1·w lure 111 the S('lllil-lif,•r('ll" f'pithelium and the relative location o( tight junctions to adhcrens junctions .1nd rlcsmosomes. Tigilt jumtions tT)sl .1rc iornwd lwtvl"l't--'11 .Hit,rtr·nt Scrtoli cell:, dt the b<1sa.l compartment of the seminiferou:. epithelium near the ba~all._unrn,J_ Three drtrerent I) integral mcmhr,1ne pmteim ,md .rr' .I lTd\' of pcriphPr.ll membrane protcrns have been identified at the site of Tjs in the testis.