Objectives: 

Successful pregnancy depends on renewal of syncytiotrophoblast (STB), the multinucleated epithelium of the placenta, by proliferation, differentiation and fusion of cytotrophoblast cells. This cell turnover is regulated by hCG, itself produced by differentiated STB. In many tissues cell turnover and endocrine secretion are regulated by K+ channels. We tested the hypothesis that activation of IKCa, which are functionally expressed by STB, regulate hCG secretion from placental villous tissue.

Materials: 

Villous tissue from normal pregnancy was maintained in explant culture (6%O2; normoxic for term placenta) for 6 days. Culture medium was collected to measure hCG secretion and lactate dehydrogenase (LDH) release (marker of necrosis). On days 3-5, explants were untreated (control) or treated with 100uM DCEBIO (IKCa activator). At day 6, tissue was lysed in H2O and hCG measured to indicate intracellular levels. The effect of DCEBIO on K+ permeability was assessed at day 6 using 86Rb efflux (marker of K+ permeability) over 20min to calculate the tissue rate constant (ln(86Rb in tissue at time t/86Rb in tissue at start)).

Results: 

DCEBIO significantly increased the 86Rb rate constant (p<0.005 vs control, linear regression, n=5) consistent with activation of IKCa. Tissue 86Rb (K+) following DCEBIO treatment was 43% lower than control (p<0.03, paired t-test, n=5). hCG secretion at day 6 was reduced by 36% in DCEBIO treated explants (p<0.03, Wilcoxon signed rank test vs control, n=6) which was associated with elevated intracellular hCG (1.3-fold, n=3). LDH release was unaffected by DCEBIO.

Conclusions: 

IKCa activated by DCEBIO inhibited hCG secretion by placental tissue. Inhibition may be direct, by blocking the secretory mechanism, or indirect by compromising STB renewal. We showed previously that activation of IKCa inhibits hCG secretion and mutinucleation of cytotrophoblast cells in culture. Future studies will address whether activation of IKCa dysregulates STB renewal and underlies abnormal renewal associated with pregnancy disease.