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

Am J Obstet Gynecol. 1997 Jul;177(1):196-209. doi: 10.1016/s0002-9378(97)70462-9.

Abstract

Objectives: 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.

Study design: Primary tissue culture of human term placental cells was performed.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Death / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Electrophoresis, Agar Gel
  • Estradiol / pharmacology*
  • Female
  • Humans
  • Lipid Peroxides / analysis
  • Lipid Peroxides / metabolism
  • Lipoproteins, LDL / analysis
  • Lipoproteins, LDL / metabolism*
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Oxidation-Reduction
  • Oxidative Stress
  • Placenta / cytology*
  • Placenta / drug effects
  • Placenta / metabolism*
  • Pregnancy
  • Progesterone / pharmacology*
  • Testosterone / pharmacology*
  • Thiobarbituric Acid Reactive Substances / analysis
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Trophoblasts / cytology
  • Trophoblasts / drug effects
  • Trophoblasts / metabolism

Substances

  • Lipid Peroxides
  • Lipoproteins, LDL
  • Thiobarbituric Acid Reactive Substances
  • Testosterone
  • Progesterone
  • Estradiol