17beta-Estradiol, progesterone, and testosterone inversely modulate low-density lipoprotein oxidation and cytotoxicity in cultured placental trophoblast and macrophages.

Abstract

We have previously shown that low-density lipoprotein oxidation is diminished by 17beta-estradiol and enhanced by progesterone and testosterone. In these experiments we wished to learn whether sex hormone effects on low-density lipoprotein oxidation alter placental cell viability in primary tissue culture. Primary tissue culture of human term placental cells was performed. Addition of 17beta-estradiol decreased low-density lipoprotein oxidation (measured as lipid peroxides, thiobarbituric acid-reacting substances, and low-density lipoprotein electrophoretic mobility) and placental cell toxicity (measured as chromium 51 release) with maximum reductions of 28% (macrophages) (p < 0.05) and 26% (trophoblasts) (p < 0.01). Conversely, progesterone and testosterone increased low-density lipoprotein oxidation and chromium 51 release, the latter a maximum of 28% and 18%, respectively, for progesterone and testosterone in macrophages (p < 0.05 in both instances) and 23% in trophoblasts (p < 0.05, testosterone only). Collectively, cytotoxicity was proportional to low-density lipoprotein oxidation and estradiol, progesterone, and testosterone concentrations. Estradiol inhibits placental macrophage- and trophoblast-mediated low-density lipoprotein oxidation and cytotoxicity, whereas progesterone and testosterone promote these effects. Sex steroid hormones may modulate the effects of oxidative stress on placental function in pregnancy.