Hum. Reprod. Advance Access published online on August 20, 2008
Human Reproduction, doi:10.1093/humrep/den317
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Expression of stathmin, a microtubule regulatory protein, is associated with the migration and differentiation of cultured early trophoblasts
1 Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan 2 Yoneyama Maternity Hospital, 2-12 Shinchou, Hachioji, Tokyo 192-0065, Japan 3 Department of Obstetrics and Gynecology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan
4 Correspondence address. Tel/Fax: +81-42-676-4536; E-mail: hiro{at}ps.toyaku.ac.jp
BACKGROUND: The microtubule-destabilizing protein stathmin is expressed by the villous cytotrophoblasts and invasive extravillous trophoblasts (EVTs) in the first-trimester human placenta. Here, we evaluated the significance of stathmin expression in terms of the functions of trophoblasts.
METHODS: We employed two choriocarcinoma cell lines (BeWo and JEG-3), an EVT cell line (HTR-8/SVneo) and isolated first-trimester trophoblast cells. The effects of small-interfering (si) RNA-mediated stathmin knockdown on trophoblast proliferation and migration were measured by WST-1 and Transwell assays, respectively. Trophoblast differentiation was induced by dibutyryl (db)-cAMP treatment and evaluated by measuring human chorionic gonadotrophin β (hCGβ) and syncytin expression and cell fusion. We examined the effect of knockdown and induced stathmin expression on db-cAMP-induced differentiation.
RESULTS: siRNA-induced silencing of stathmin expression had a marked inhibitory effect on BeWo, JEG-3 and HTR-8/SVneo cell migration and also suppressed their proliferation, albeit to a lesser extent. db-cAMP-enhanced hCGβ and syncytin expression and cell fusion in BeWo cells was inhibited by stathmin knockdown. However, induced expression of stathmin reversed the hCGβ and syncytin expression and cell fusion in the Tet-On BeWo cells. Suppression of stathmin expression also inhibited the migration of and hCGβ production by first-trimester trophoblasts.
CONCLUSIONS: Stathmin expression may be closely associated with early trophoblast migration and differentiation into syncytiotrophoblasts during placentation.
Key words: stathmin/trophoblast/placenta/syncytiotrophoblast/extravillous trophoblast
Submitted on October 16, 2007; resubmitted on July 22, 2008; accepted on July 24, 2008.
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