Silver nanoparticles suppress forskolin-induced syncytialization in BeWo cells

Abstract

Opportunities for the exposure of pregnant women to engineered nanoparticles have been increasing with the expanding use of these materials. Therefore, there are concerns that nanoparticles could have adverse effects on the establishment and maintenance of pregnancy. The effects of nanoparticles on the mother and fetus have been evaluated from this perspective, but there is still little knowledge about the effects on placentation and function acquisition, which are essential for the successful establishment and maintenance of pregnancy. Formation of the syncytiotrophoblast is indispensable for the acquisition of placental function, and impairment of syncytialization inevitably affects pregnancy outcomes. Here, we assessed the effect of nanoparticles on placental formation by using forskolin-treated BeWo cells, a typical in vitro model of trophoblast syncytialization. Immunofluorescence staining analysis revealed that silver nanoparticles with a diameter of 10 nm (nAg10) (at 0.156 µg/mL) significantly decreased the proportion of syncytialized BeWo cells, but gold nanoparticles with a diameter of 10 nm did not. Consistently, only nAg10 (at 0.156 µg/mL) significantly suppressed forskolin-induced elevation of CGB and SDC1 mRNA expression levels and human chorionic gonadotropin β production in a dose-dependent manner; these molecules are all markers of syncytialization. Besides, nAg10 significantly decreased the expression of ERVFRD-1, which encodes proteins associated with cell fusion. Moreover, nAg10 tended to suppress the expression of sFlt-1 e15a, a placental angiogenesis marker. Collectively, our data suggest that nAg10 could suppress formation of the syncytiotrophoblast and that induce placental dysfunction and the following poor pregnancy outcomes.

Keywords:

• Nanoparticles
• placenta
• syncytialization
• trophoblast

Author contributions

Y.S. and K.H. designed the study; R.Is., R.Iz., J.S., A.F., and A.Y-U. performed experiments and analyzed data; Y.S. and K.H. wrote the manuscript; H.T., Y.H., and A.N. provided technical support and conceptual advice; Y.T. supervised all projects. All authors discussed the results and commented on the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data generated or analyzed during this study are included in this published article and its supplementary information files.

Additional information

Funding

This research was partially supported by the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from the Japan Agency for Medical Research and Development under [Grant Number JP21am0101084]. This study was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science [no. 19K19409 to K.H.]; by a Health Labor Sciences Research Grant from the Ministry of Health, Labor and Welfare of Japan [no. 21KD1002 to Y.T.]; and by Support for Pioneering Research Initiated by the Next Generation from the Japan Science and Technology Agency [no. JPMJSP2138 to Y.S.].