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Angiogenesis, proteases and angiogenic factors during the inception of pregnancy. Crucial contributors or trivial bystanders?

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(1)Angiogenesis, proteases and angiogenic factors during the inception of pregnancy. Crucial contributors or trivial bystanders? Plaisier, G.M.. Citation Plaisier, G. M. (2008, May 7). Angiogenesis, proteases and angiogenic factors during the inception of pregnancy. Crucial contributors or trivial bystanders?. Retrieved from https://hdl.handle.net/1887/12861 Version:. Corrected Publisher’s Version. License:. Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden. Downloaded from:. https://hdl.handle.net/1887/12861. Note: To cite this publication please use the final published version (if applicable)..

(2) $PMPVS'JHVSFT.

(3)

(4) $PMPVS¹HVSFT. $)"15&3 Sprouting. Intussusception. Elongation. 'JHVSF&OEPNFUSJBMBOHJPHFOFTJTQSPDFFETCZFMPOHBUJPOBOEJOUVTTVTDFQUJPOSBUIFSUIBOCZDMBTTJDBM TQSPVUGPSNBUJPO"EBQUFEGSPN3PHFST. .

(5) $)"15&3. B. C. D 100 75.  . 50 #. 25 0.  Control uPA BB94 uPA +BB94. mean tube length (% of control). . mean tube length (% of control). $PMPVS¹HVSFT. A. E 100 75 50 25 0.   Control uPA BB94 uPA +BB94. 'JHVSF$BQJMMBSZMJLFUVCFGPSNBUJPOCZI&.7&$JOB¹CSJOPSDPMMBHFONBUSJYEFQFOETPOV1"BOE..1 BDUJWJUJFT I&.7&$XFSFDVMUVSFEPOUPQPGBUISFFEJNFOTJPOBM¹CSJONBUSJY " $ % PS¹CSJODPMMBHFOUZQF NBUSJY # & BOETUJNVMBUFEXJUI7&('" OHN- "BOE#.JDSPHSBQITUBLFOBGUFSEBZTPGDVMUVSJOH JOTFUTJO"BOE#TIPXEFUBJMTPGDBQJMMBSZMJLFTUSVDUVSFT#BSμN #BSJOTFUTμN$$SPTT TFDUJPOQFSQFOEJDVMBSUPUIFNBUSJYTVSGBDFBOETUBJOFEXJUI)FNBUPYZMJO1IMPYJOF4BGSBO CBSμN  %BOE&I&.7&$XFSFDVMUVSFEXJUIOHN-7&('" DPOUSPM JOUIFBCTFODFPSQSFTFODFPGQPMZDMPOBM BOUJV1" αV1"   μHN-  ##  μHN-  PS B DPNCJOBUJPO PG ## BOE BOUJV1" "GUFS  EBZT PGDVMUVSJOH NFBOUVCFMFOHUIXBTNFBTVSFECZJNBHFBOBMZTJT5IFEBUBJOQBOFM%BSFFYQSFTTFEBTB QFSDFOUBHF PG 7&('"JOEVDFE UVCF GPSNBUJPO ± 4&. PG  JOEFQFOEFOU FYQFSJNFOUT PG EVQMJDBUF XFMMT QFSGPSNFEXJUIEJGGFSFOUI&.7&$JTPMBUJPOT1BOFM&SFQSFTFOUTFYQFSJNFOUT∗1WTDPOUSPM  1WTαV1".

(6) $PMPVS¹HVSFT. kD. A. 92. -MMP-9. active MT1-MMP 8 (ng/mL). B. 7. 72 64. kD. 3. -pro-MMP-2 -act. MMP-2. 642. 55. -MMP-1/3. M. Con TNF PMA VEGF. D. C. 1 0. MT3MMP. 46-. Con VEGF TNF V/T Con. VEGF TNF PMA. E. 'JHVSFI&.7&$FYQSFTTWBSJPVT..1TBOE.5..1T I&.7&$XFSFDVMUVSFEGPSIJO.TVQQMFNFOUFEXJUI)4" " PS)4 # $ BOEXFSF OPU TUJNVMBUFE DPOUSPM  PS TUJNVMBUFE XJUI 5/'α  OHN-  7&('"  OHN-  PS 1."  .  BTJOEJDBUFE"(FMBUJO[ZNPHSBQIZPGIDPOEJUJPOFENFEJVN .MBEEFS #.5..1BDUJWJUZJO DFMMMZTBUFT NFBO‘SBOHFPGUXPFYQFSJNFOUTQFSGPSNFEJOEVQMJDBUFXFMMTXJUIUXPEJGGFSFOUJTPMBUJPOT EFUFDUJPOMJNJUPGUIFBTTBZOHN- $8FTUFSOCMPUPG.5..1JOIDPOEJUJPOFENFEJVN%BOE &*NNVOPIJTUPDIFNJDBMBOBMZTJTPG.5..1JOFOEPNFUSJBMUJTTVFTIPXTUIFQSFTFODFPG.5..1JO FOEPUIFMJBMDFMMT % BSSPXT BOENZPNFUSJVN & TUBST . .

(7) $)"15&3. A Total Vascular Surface (mm 2/mm 2). 0,06. . 0,05 0,04 0,03 0,02 0,01 0 EP. #. #. #. 200. Luminal surface (um /vessel). 250. LS. M. ES. LS. M. 600 500.  $. 2. 2. Number of vessels / mm. $PMPVS¹HVSFT. ES. D. C. . LP. 150 100 50 0 EP. LP. ES. LS. M. 400 300 200 100 0 EP. LP. 'JHVSF7BTDVMBSJTBUJPOQBUUFSOJODZDMJOHIVNBOFOEPNFUSJVN 5IF WBTDVMBSJTBUJPO QBUUFSO JO IVNBO FOEPNFUSJVN XBT EFUFSNJOFE CZ JNBHF BOBMZTJT PG BOUJ$% TUBJOFETFDUJPOT4JY¹FMETQFSCJPQTZXFSFTDBOOFEBUYNBHOJ¹DBUJPO"$%BOUJHFOFYQSFTTJPOJO FOEPUIFMJBMDFMMTJOMBUFQSPMJGFSBUJWFFOEPNFUSJVN CBSμN #5IFUPUBMWBTDVMBSTVSGBDF NNNN  $UIFOVNCFSPGWFTTFMTQFSNNBOE%UIFMVNJOBMTVSGBDF μNWFTTFM XFSFDBMDVMBUFEGPSFBDITBNQMF BOEFYQSFTTFEBTNFBO‘4&.&1&BSMZQSPMJGFSBUJWFQIBTF O -1-BUFQSPMJGFSBUJWFQIBTF O &4 &BSMZTFDSFUPSZQIBTF O -4-BUFTFDSFUPSZQIBTF O .NFOTUSVBMQIBTF O •QWFSTVT &1 &4BOE-4#QWFSTVT&1 &4∗QWFSTVT&4 -4BOE.BOEQWFSTVT&4 -4BOE..

(8) $PMPVS¹HVSFT. A. MT1-MMP. B. MT1-MMP + actin. G. MT4-MMP. C. MT2-MMP. D. MT2-MMP + actin. H. v WF. E. MT3-MMP. F. MT3-MMP + actin. I. Lysotracker. 'JHVSF.5..1BOUJHFOFYQSFTTJPOTJOI&.7&$ &OEPUIFMJBM .5..1 FYQSFTTJPO XBT EFUFSNJOFE CZ ºVPSFTDFODF NJDSPTDPQZ NBHOJ¹DBUJPO Y  5IF FYQSFTTJPOPG.5..1 ‘BDUJO" # .5..1 ‘BDUJO$ % .5..1 ‘BDUJO& ' .5..1 (  WPO8JMMFCSBOE'BDUPSJO8FJCFM1BMBEFCPEJFT ) BOE-ZTPUSBDLFSJOMZTPTPNFT * JODVMUVSFEFOEPNFUSJBM FOEPUIFMJBMDFMMT I&.7&$ 5IFOFHBUJWFDPOUSPMPOMZTIPXFECMVFTUBJOJOHPGUIFOVDMFJ OPUTIPXO #MVF %"1*JOOVDMFJ HSFFOUBSHFUQSPUFJO SFEBDUJOPSMZTPUSBDLFS. .

(9) Mean Staining Index. A. 4. 3. 2. 1. 0 MT2-MMP. MT3-MMP. C. MT2-MMP. D. MT3-MMP. E. MT4-MMP. $PMPVS¹HVSFT. B. MT1-MMP. MT4-MMP. . 'JHVSF.5..1BOUJHFOFYQSFTTJPOTJOFOEPNFUSJBMFOEPUIFMJVNBOEPUIFSDFMMUZQFT 5IF FYQSFTTJPO PG .5..1 BOUJHFOT CZ FOEPNFUSJBM FOEPUIFMJBM DFMMT XBT EFUFSNJOFE CZ JNNVOPIJTUPDIFNJTUSZ".5..1BOUJHFOFYQSFTTJPOTJOFOEPUIFMJBMDFMMTFYQSFTTFEQFSDZDMFQIBTFBT NFBOTUBJOJOHJOEFY‘4&. BMMQ 5IFTUBJOJOHJOEFYJTNJOJNBMMZ OPTUBJOFEDFMMT BOENBYJNBMMZ  TUSPOHMZTUBJOFEDFMMT #.5..1BOUJHFOEFUFDUFEJO14.$T PQFOBSSPX CVUOPUJOFOEPUIFMJBM DFMMT BSSPXT JOMBUFQSPMJGFSBUJWF -1 FOEPNFUSJVN$.5..1BOUJHFOFYQSFTTJPOJOFOEPUIFMJVNJO-1 FOEPNFUSJVN BSSPX %.5..1FYQSFTTJPOJOFOEPUIFMJBMDFMMT BSSPXT BOETUSPNBMDFMMT PQFOBSSPX  JO-1FOEPNFUSJVN&.5..1FYQSFTTJPOJOFOEPUIFMJBMDFMMT BSSPX JO-1FOEPNFUSJVN'/FHBUJWF DPOUSPM#BSμN &BSMZQSPMJGFSBUJWFQIBTF O  -BUFQSPMJGFSBUJWFQIBTF O  &BSMZTFDSFUPSZQIBTF O. -BUFTFDSFUPSZQIBTF O  NFOTUSVBMQIBTF O .

(10) $PMPVS¹HVSFT. $)"15&3 DB. DSE. DP. DB. Õ. DP. Õ. DSE. Õ. Cytokeratin. A. B. C. 0,08. 5000. *. . *. . 2. 0,06. 2. 125. Vascular Surface (mm /mm ). 2. Number of vessels / mm. 150. Luminal Surface (um 2/vessel). CD34. 100. 75 50. 25 0. 0,04. 0,02. DP. DB. . 3000. 2000. 1000. 0. 0. DSE. * 4000. DSE. DP. DB. DSE. DP. DB. 'JHVSF$ZUPLFSBUJOFYQSFTTJPOBOEWBTDVMBSJTBUJPOJOUIFUISFFEFDJEVBMUJTTVFT %JGGFSFOUJBUJPO CFUXFFO UISFF EFDJEVBM UJTTVFT XBT PCUBJOFE CZ )14 BOE BOUJDZUPLFSBUJO TUBJOJOH UPQ QBOFM  %4& BOE %1 FYQSFTTFE DZUPLFSBUJO POMZ JO HMBOEVMBS FQJUIFMJBM DFMMT DMPTFE BSSPXT  XIFSFBT DZUPLFSBUJOJTBMTPFYQSFTTFEJOFYUSBWJMMPVTUSPQIPCMBTUTPG%# PQFOBSSPXT 5IFWBTDVMBSJTBUJPOQBUUFSO JOIVNBOEFDJEVBMUJTTVFTXBTEFUFSNJOFECZJNBHFBOBMZTJTPGBOUJ$%TUBJOFETFDUJPOT NJEEMFBOE CPUUPNQBOFM $%BOUJHFOFYQSFTTJPOJOFOEPUIFMJBMDFMMT BSSPXT PG%4& %1BOE%#XBTDPNQBSFE XJUIJOTVCKFDUT%BUBXFSFBOBMZTFEVTJOHUIFSFQFBUFENFBTVSFT"/07""5IFOVNCFSPGWFTTFMTQFS NN #UIFWBTDVMBSTVSGBDFQFSBSFB NNNN BOE$UIFMVNJOBMTVSGBDF μNWFTTFM XFSFDBMDVMBUFE BOEFYQSFTTFEBTNFBO‘4&.∗Q♦Q#BSμN. .

(11) $PMPVS¹HVSFT . 'JHVSF1SPUFJOFYQSFTTJPOPGBOHJPHFOJDGBDUPSTJOFOEPUIFMJVNPGFBSMZ¹STUUSJNFTUFSEFDJEVB 5IFQSPUFJOFYQSFTTJPOPGBOHJPHFOJDGBDUPSTXBTEFUFSNJOFEJO%4& %1BOE%#'SJFENBOUFTU BOPO QBSBNFUSJDBMUFTUGPSQBJSFETBNQMFT BOEUIF8JMDPYPOUFTUXFSFVTFEGPSTUBUJTUJDBMBOBMZTJT"1SPUFJO FYQSFTTJPOPGFBDIBOHJPHFOJDGBDUPSJOFOEPUIFMJVNXBTFYQSFTTFEBTUIFNFBOTUBJOJOHJOEFY‘4&.BOE #)TIPXFYBNQMFTPGUIFTFFYQSFTTJPOT#&OEPUIFMJBM7&('FYQSFTTJPOXBTOPUEFUFDUBCMFJO%#$1M(' XBT FYQSFTTFE JO FQJUIFMJVN PQFO BSSPX  BOE FOEPUIFMJVN DMPTFE BSSPX  PG %# % &OEPUIFMJBM ,%3 FYQSFTTJPO DMPTFEBSSPX BOETUSPNBM,%3FYQSFTTJPO PQFOBSSPX JO%#&&OEPUIFMJBM'MUFYQSFTTJPO JO%# BSSPX '"OHJPQPJUFJOJO%#XBTEFUFDUFEJOFQJUIFMJVN PQFOBSSPX CVUOPUJOTUSPNBMBOE FOEPUIFMJBM DFMMT DMPTFE BSSPX  ( &OEPUIFMJBM BOHJPQPJFUJO FYQSFTTJPO JO %# BSSPX  ) &OEPUIFMJBM 5*&FYQSFTTJPOJO%# BSSPX  %4&  %1  %##BSμN FYDFQU'μN .

(12) $PMPVS¹HVSFT. 'JHVSF1SPUFJOFYQSFTTJPOPGBOHJPHFOJDGBDUPSTJOFYUSBWJMMPVTUSPQIPCMBTUT &75 PGFBSMZ¹STUUSJNFTUFS EFDJEVB 5IFQSPUFJOFYQSFTTJPOPGBOHJPHFOJDGBDUPSTJO&75JOEFDJEVBCBTBMJT %# XBTTUVEJFEJOTFSJBMTFDUJPOT TUBJOFEBHBJOTUDZUPLFSBUJOBOEUIFUBSHFUQSPUFJO"1SPUFJOFYQSFTTJPOJO&75XBTFYQSFTTFEBTUIFNFBO TUBJOJOHJOEFY‘4&.#$ZUPLFSBUJO BSSPXT BOE$TFSJBM1M('FYQSFTTJPO BSSPXT JO&75#BSμN. 'JHVSF  7BTDVMBSJTBUJPO QBUUFSO BOE FOEPUIFMJBM QSPUFJO FYQSFTTJPO JO FBSMZ WFSTVT MBUF ¹STU USJNFTUFS EFDJEVB 5IFWBTDVMBSJTBUJPOQBUUFSOJOIVNBOFBSMZ CMBDLCBST BOEMBUF XIJUFCBST ¹STUUSJNFTUFSEFDJEVBMUJTTVFT XBTEFUFSNJOFECZJNBHFBOBMZTJTPGBOUJ$%TUBJOFETFDUJPOT%BUBXFSFBOBMZTFEVTJOHUIFSFQFBUFE NFBTVSFT"/07""5IFOVNCFSPGWFTTFMTQFSNN #UIFWBTDVMBSTVSGBDFQFSBSFB NNNN BOE$ UIFMVNJOBMTVSGBDF μNWFTTFM XFSFFYQSFTTFEBTNFBO‘4&.7&('FYQSFTTJPOXBTOPUEFUFDUBCMFJO FBSMZ¹STUUSJNFTUFSFOEPUIFMJVNPG%# BSSPX % XIFSFBTUIFFYQSFTTJPOXBTQSFTFOUJOMBUF¹STUUSJN FOEPUIFMJVNPG%# BSSPX & &BSMZ¹STUUSJNFTUFSBOEMBUF¹STUUSJNFTUFS#BSμN ∗Q. .

(13) B. C. Õ. Õ. A. Õ. $)"15&3. Õ E. $PMPVS¹HVSFT. Õ. Õ . F. Õ. D. 'JHVSF1SPUFJOMFWFMTPGQSPUFBTFTJOFBSMZ¹STUUSJNFTUFSEFDJEVB 5IFMFWFMPGQSPUFBTFTXBTEFUFSNJOFEJO%4& %1BOE%#".5..1BOUJHFOXBTEFUFDUBCMFJOFQJUIFMJBM PQFO BSSPX  FOEPUIFMJVN DMPTFE BSSPX  BOE TUSPNBM DFMMT DMPTFE BSSPXIFBE  PG %4& # .5..1 BOUJHFOJOFQJUIFMJVN PQFOBSSPX TUSPNBMDFMMT DMPTFEBSSPXIFBE BOEQFSJDZUFT PQFOBSSPXIFBE PG %# $ &QJUIFMJBM PQFO BSSPX  BOE TUSPNBM DMPTFE BSSPXIFBE  .5..1 BOUJHFO JO %# 1FSJDZUFT OPU QSFTFOU JO UIJT ¹FME % .5..1 BOUJHFO JO FQJUIFMJVN PQFO BSSPX  BOE POMZ EJNMZ JO TUSPNBM DFMMT DMPTFEBSSPXIFBET PG%1&V1"BOUJHFOJOFQJUIFMJVN PQFOBSSPX TUSPNBMDFMMT DMPTFEBSSPXIFBE  BOE FOEPUIFMJVN DMPTFE BSSPXT  JO %# 1FSJDZUFT OPU QSFTFOU JO UIJT ¹FME ' &QJUIFMJBM PQFO BSSPX  FOEPUIFMJBM DMPTFEBSSPXT BOETUSPNBMDFMMT DMPTFEBSSPXIFBET V1"3QSPUFJOJO%#"% '#BS μN &#BSμN.

(14) $PMPVS¹HVSFT. A. 1,8 M ea n Sta ining Index. 1,6. DSE. 1,4. DP. 1,2. DB. 1 0,8 0,6 0,4 0,2 0 MT 1-MMP MT 2-MMP MT 3-MMP MT 5-MMP. B. C. E. uPA. uPAR. D. F. Õ 'JHVSF1SPUFJOMFWFMTPGQSPUFBTFTJOFOEPUIFMJVNPGFBSMZ¹STUUSJNFTUFSEFDJEVB "1SFTFODFPGQSPUFBTFBOUJHFOTJOFOEPUIFMJVN &$ XBTFYQSFTTFEBTUIFNFBOTUBJOJOHJOEFY‘4&.BOE #'TIPXFYBNQMFTPGFOEPUIFMJBMQSPUFBTFFYQSFTTJPO#&OEPUIFMJBM BSSPXT BOETUSPNBM BSSPXIFBET  .5..1XBTEFUFDUBCMFJO%#$.5..1XBTEFUFDUFEJOFOEPUIFMJVN BSSPXT PG%#%&OEPUIFMJBM .5..1 BOUJHFO BSSPXT  JO %4& & V1" BOUJHFO JO FOEPUIFMJVN DMPTFE BSSPXT  FQJUIFMJVN PQFO BSSPX BOETUSPNBMDFMMT BSSPXIFBE JO%#'V1"3JO%#XBTEFUFDUFEJOFOEPUIFMJBMDFMMT BSSPXT BOE TUSPNBMDFMMT BSSPXIFBET #'#BSμN. .

(15) A. SynCTB. 7. CTB. Mean Staining Index. 6 5 4 3 2 1 0 MT 1MMP. MT 3MMP. MT 5MMP. uPA. uPAR. D. uPA. C. Cytokeratin. Õ. Õ. B. uPAR. MT 2MMP. A. CD56. *. Early 1st trimester 20. *. * *. Late 1st trimester. 15 10 5 0 DSE. DP. 4 M ea n % po sitiv e cells/stro m a l cells. 25 M ea n % po sitiv e cells/stro m a l cells. $PMPVS¹HVSFT. Õ. . 'JHVSF1SPUFJOMFWFMTPGQSPUFBTFTJOWJMMPVTBOEFYUSBWJMMPVTUSPQIPCMBTUT &75 PGFBSMZ¹STUUSJNFTUFS EFDJEVB 5IF QSFTFODF PG QSPUFBTF BOUJHFOT JO WJMMPVT BOE FYUSBWJMMPVT USPQIPCMBTUT JO EFDJEVB CBTBMJT %#  XBT TUVEJFEJOTFSJBMTFDUJPOTTUBJOFEBHBJOTUDZUPLFSBUJOBOEUIFUBSHFUQSPUFJO"*NNVOPTUBJOJOHJOTZODZUJP BOEDZUPUSPQIPCMBTUT TZO$5#BOE$5# XBTFYQSFTTFEBTUIFNFBOTUBJOJOHJOEFY‘4&.#BOE$V1"3 BOEDZUPLFSBUJOBOUJHFOTJOTFSJBMFYQSFTTJPOJO&75 DMPTFEBSSPXT BOEFQJUIFMJVN PQFOBSSPXT %V1" BOUJHFOT JO TZODZUJPUSPQIPCMBTU PQFO BSSPX  BOE OPU JO DZUPUSPQIPCMBTU DMPTFE BSSPX  #% #BS   μN. DB. 3,5 3. B. CD68 Early 1st trimester Late 1st trimester. 2,5 2 1,5 1 0,5 0 DSE. DP. DB. D. CD68. C. CD56. E. Negative. 'JHVSF$%BOE$%QPTJUJWFDFMMTJOFBSMZBOEMBUF¹STUUSJNFTUFSEFDJEVB " $%QPTJUJWF DFMMT JO EFDJEVB  FYQSFTTFE BT UIF NFBO OVNCFS PG QPTJUJWF DFMMT QFS UPUBM OVNCFS PG TUSPNBMDFMMT NFBO‘4% #$%QPTJUJWFDFMMTJOEFDJEVB FYQSFTTFEBTUIFNFBOOVNCFSPGQPTJUJWF DFMMTQFSUPUBMOVNCFSPGTUSPNBMDFMMT NFBO‘4% $$%FYQSFTTJPOJOEFDJEVBCBTBMJT CBSμN #MPXVQTIPXT$%

(16) DFMMT BSSPXT TVSSPVOEJOHBWFTTFMBOEHMBOE CBSμN%$%QPTJUJWFDFMM BSSPX JOEFDJEVBQBSJFUBMJT CBSμN&/FHBUJWFDPOUSPM CBSμN QWFSTVT%4&.

(17) $PMPVS¹HVSFT. DSE. Õ Õ Decidual Secretory Endometrium (DSE) DSE versus DB Extravillous Trophoblast Pregnancy-induced Hormones * Uterine NK cells. DSE versus DP Pregnancy-induced Hormones * Uterine NK cells. Decidua Parietalis (DP). DP. Decidua Basalis (DB). DP versus DB Extravillous Trophoblast. DB. Õ Õ 'JHVSF)VNBO¹STUUSJNFTUFSEFDJEVBMUJTTVFT 3FQSFTFOUBUJPO PG UIF JOºVFODFT PG JNNVOF DFMMT  FYUSBWJMMPVT USPQIPCMBTU BOE QSFHOBODZJOEVDFE IPSNPOFT I$( PFTUSBEJPMBOEQSPHFTUFSPOF PO¹STUUSJNFTUFSEFDJEVBMUJTTVFT%JGGFSFOUJBUJPOCFUXFFO EFDJEVBMTFDSFUPSZFOEPNFUSJVN %4& EFDJEVBQBSJFUBMJT %1 BOECBTBMJT %# XBTPCUBJOFECZ)14 BOEDZUPLFSBUJOTUBJOJOH%4&BOE%1FYQSFTTDZUPLFSBUJOJOHMBOEVMBSFQJUIFMJVN PQFOBSSPXT XIFSFBT DZUPLFSBUJOJTBMTPFYQSFTTFEJO&75 DMPTFEBSSPXT PG%##BSμN. .

(18) $)"15&3 2. #. N u m b er o f vessels p er m m. 140 120 100 80. . 60 40 20 0. $PMPVS¹HVSFT. DSE. . . DP. DB. B. #. C. #. 0,08 0,07 0,06 0,05 0,04 0,03 0,02 0,01 0 DSE. DP. DB. L u m in al S u rface (u m 2 /vessel). 2. #. T o tal Vascu lar Su rface p er m m. A 160. #. #. 7000. . 6000.  . 5000 4000 3000 2000 1000 0 DSE. Cases Decidua basalis. Cases Decidua parietalis. Controls Decidua basalis. Controls Decidua parietalis. DP. DB. 'JHVSF7BTDVMBSJTBUJPOQBUUFSOJODBTFTBOEDPOUSPMT 5IFWBTDVMBSJTBUJPOQBUUFSOJOEFDJEVBMUJTTVFTPGDPOUSPMT O CMBDLCBST BOEDBTFT O XIJUFCBST  XBTEFUFSNJOFECZJNBHFBOBMZTJTPGBOUJ$%TUBJOFETFDUJPOT"7FTTFMEFOTJUZ OVNCFSPGWFTTFMTQFS NN #UIFUPUBMWBTDVMBSTVSGBDF NNNN BOE$UIFMVNJOBMTVSGBDF μNWFTTFM XFSFDBMDVMBUFE BOE FYQSFTTFE BT NFBO‘4&.  Q XJUIJO DPOUSPMT  ∗ Q JO DBTFT WFSTVT DPOUSPMT 5IF CPUUPN QBOFMTTIPXFYBNQMFTPGWBTDVMBSJTBUJPOJOEFDJEVBQBSJFUBMJTBOECBTBMJTPGDBTFTBOEDPOUSPMT.

(19) $PMPVS¹HVSFT. Controls. Cases. Ang-1. Flt-1. MT5-MMP. Negative. 'JHVSF"OUJHFOQSFTFODFPGBOHJPHFOJDGBDUPSTBOEQSPUFBTFTJODBTFTBOEDPOUSPMT &YBNQMFTPGUIFBOUJHFOFYQSFTTJPOPG"OH 'MUBOE.5..1JODPOUSPMT MFGUTJUFPGQBOFM BOEDBTFT SJHIUTJUFPGQBOFM "OHBOUJHFOQSFTFODFJOFQJUIFMJBMDFMMT PQFOBSSPX JO%#PGDPOUSPMT DPNQBSFEUP UIFJSQSFTFODFJOTUSPNBM DMPTFEBSSPX FQJUIFMJBMDFMMT PQFOBSSPX BOE14.$ PQFOBSSPXIFBE JO%# PGDBTFT'MUBOUJHFOQSFTFODFJOFQJUIFMJBMDFMMT PQFOBSSPX BOETUSPNBMDFMMT DMPTFEBSSPX JO%#PG DPOUSPMT DPNQBSFEUPUIFJSFMFWBUFEQSFTFODFJO%#PGDBTFT/PWBTDVMBUVSFQSFTFOUJOUIFTF¹MFET. ..1BOUJHFOTJOFQJUIFMJBMDFMMT PQFOBSSPX JO%#PGDPOUSPMT DPNQBSFEUPUIFJSQSFTFODFJO14.$ PQFO BSSPXIFBE FOEPUIFMJBM DMPTFEBSSPXIFBE TUSPNBM DMPTFEBSSPX JO%#PGDBTFT/FHBUJWFDPOUSPMTVTJOH OPOJNNVOFNPVTF*H( MFGU BOEPNJTTJPOPGUIF¹STUBOUJCPEZ SJHIU "MMQBOFMTCBSμN. .

(20) Controls. Cases. Flt-1. $PMPVS¹HVSFT. KDR. MT2-MMP. . 'JHVSF"OUJHFOQSFTFODFPGBOHJPHFOJDGBDUPSTBOEQSPUFBTFTJOFOEPUIFMJVNJODBTFTBOEDPOUSPMT 5IFQSPUFJOFYQSFTTJPOPGBOHJPHFOJDGBDUPSTBOEQSPUFBTFTXBTEFUFSNJOFEJO%4& %1BOE%#PGDBTFT BOEDPOUSPMTWJBJNNVOPIJTUPDIFNJTUSZ&YBNQMFTPGUIFEJGGFSFOUJBMFOEPUIFMJBMFYQSFTTJPO BSSPXIFBET  PGºU ,%3BOE.5..1CFUXFFODBTFT SJHIUTJUFPGQBOFM BOEDPOUSPMT MFGUTJUFPGQBOFM BSFHJWFO 'MU &MFWBUFE ºU FYQSFTTJPO JO FOEPUIFMJBM DFMMT JO %# PG DBTFT DPNQBSFE UP DPOUSPMT ,%3 &MFWBUFE ,%3FYQSFTTJPOJOFOEPUIFMJBMDFMMTJO%#PGDBTFTDPNQBSFEUPDPOUSPMT.5..1&MFWBUFE.5..1 FYQSFTTJPOJOFOEPUIFMJBMDFMMTJO%#PGDBTFTDPNQBSFEUPDPOUSPMT"MMQBOFMTCBSμN.

(21)

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