Increasing evidence for and regulation of a human placental endogenous digitalis-like factor

Reproductive Sciences
Jie MaS W Graves

Abstract

Endogenous digitalis-like factors (EDLFs) appear to be hypertensiogenic and increased in the serum and placenta of women with preeclampsia (PE), a complication of pregnancy. Digibind, an anti-digoxin antibody Fab fragment, reverses in vitro effects of EDLF and in vivo features of PE. We used Digibind in a radioimmunoassay to measure EDLF and compared this to a bio-functional assay of EDLF with good agreement. These methods confirmed that human placenta was a source of EDLF, synthesizing and releasing EDLF into the media of cultured human placental tissue. Ketoconazole, a steroid synthesis inhibitor, and 17-OH progesterone, a possible substrate of steroid synthesis, were shown to inhibit or increase EDLF release respectively, suggesting overlap of synthetic pathways. Abnormalities of PE such as placental hypoxia, increased reactive oxygen species and increased pro-inflammatory cytokines were demonstrated to increase placental EDLF release. These findings strongly support placental production of EDLF with increased release due to features of PE.

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Citations

Mar 13, 2016·American Journal of Obstetrics and Gynecology·Komal KediaSteven W Graves
Nov 13, 2013·American Journal of Obstetrics and Gynecology·Steven W GravesUNKNOWN Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network
Oct 9, 2014·Journal of the American Society of Nephrology : JASN·Moran Dvela-LevittDavid Lichtstein
Mar 7, 2021·International Journal of Molecular Sciences·Natalia I AgalakovaAlexei Y Bagrov

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Methods Mentioned

BETA
ELISA
antibody assay
dissection

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