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Apoptosis
Cascade Progresses during Turnover of Human Trophoblast: Analysis of Villous
Cytotrophoblast and Syncytial Fragments In Vitro |
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Berthold Huppertz,
Hans-Georg Frank, Frank Reister, John Kingdom, Hubert Korr, and Peter Kaufmann |
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Departments
of Anatomy (BH, H-GF, HK, PK), and Obstetrics and Gynecology (FR), University
of Technology, Aachen, Germany, and Department of Obstetrics and Gynecology
(JK), Mount Sinai Hospital, University of Toronto, Canada |
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SUMMARY: Growth and survival
of the trophoblast layer of the human placenta depends on continuous incorporation
of villous trophoblast stem cells (cytotrophoblast), by syncytial fusion,
into the syncytiotrophoblast. Descriptive studies suggest that this process
may be intimately related to apoptosis. We have analyzed the expression
and activation of initiator and execution caspases, critical effectors of
apoptosis, in relation to trophoblast turnover (differentiation) in human
placental villi. We used immunohistochemistry, caspase enzyme histochemistry,
caspase activity assays, Western blots, and autoradiography techniques on
placental tissue sections, trophoblast lysates, villous explants, and isolated
trophoblast fragments (villous cytotrophoblast and mononuclear syncytial
elements) in vitro. Our data demonstrate expression of initiator caspases
8 and 10 and activity of caspase 8 in villous cytotrophoblast. Proforms
of the execution caspases 3, 6, and 7 were also expressed in villous cytotrophoblast,
but activation of execution caspases 3 and 6 could only be demonstrated
in the syncytiotrophoblast after syncytial fusion. Down-regulation of the
general transcription level (reduced incorporation of [3H]uridine)
as well as cleavage of the execution caspase substrates poly-(ADP-ribose)polymerase
and lamin B was confined to syncytiotrophoblast and preceded the final events
of apoptotic death (terminal deoxynucleotidyl transferase-mediated deoxyuridine
triphosphate nick-end labeling reactivity and nuclear collapse). Our data
confirm that the apoptosis cascade in villous trophoblast is regulated in
parallel with trophoblast differentiation, syncytial fusion, and trophoblast
turnover. |
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