Advertisement

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

      Abstract

      OBJECTIVES: We have previously shown that low-density lipoprotein oxidation is diminished by 17β-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 17β-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. (Am J Obstet Gynecol 1997;177:196-209.)

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Obstetrics & Gynecology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • opp RH
        • Magee MS
        Pregnancy and parturition.
        in: 21st ed. Textbook of physiology. Saunders, Philadelphia1989: 380-407 (2. Knopp RH, Zhu X-D, Lau JR, Walden CE. Sex hormones and lipid interactions: implications for cardiovascular disease in women. Endocrinologist 1994;4:286-301)
        • Adams MR
        • Kaplan JR
        • Manuck SB
        • Koritnik DR
        • Parks JS
        • Wolfe MS
        • et al.
        Inhibition of coronary artery atherosclerosis by 17β-estradiol in ovariectomized monkeys.
        Arteriosclerosis. 1990; 10: 1051-1057
        • Haarbo J
        • Leth-Espensen P
        • Stender S
        • Christiansen C.
        Estrogen monotherapy and combined estrogen-progestogen replacement therapy attenuate aortic accumulation of cholesterol in ovariectomized cholesterol-fed rabbits.
        J Clin Invest. 1992; 87: 1274-1279
        • Adams MR
        • Williams JK
        • Kaplan JR.
        Effect of androgens on coronary artery atherosclerosis and atherosclerosis-related impairment of vascular responsiveness.
        Arterioscler Thromb Vasc Biol. 1995; 15: 562-570
        • Adams MR
        • Clarkson TB
        • Koritnik DR
        • Nash HA.
        Contraceptive steroids and coronary artery atherosclerosis in cynomolgous macaques.
        Fertil Steril. 1987; 47: 1010-1018
        • Adams MR
        • Golden DL.
        Atheroprotective effects of estrogen replacement therapy are antagonized by medroxyprogesterone acetate in monkeys.
        Circulation. 1995; 92 ([abstract]): I627
        • Mazière C
        • Auclair M
        • Ronveaux MF
        • Salmon S
        • Santus R
        • Mazière JC.
        Estrogens inhibit copper and cell-mediated modification of low density lipoprotein.
        Atherosclerosis. 1991; 89: 175-182
        • Rifici VA
        • Khachadurian AK.
        The inhibition of low density lipoprotein oxidation by 17β-estradiol.
        Metabolism. 1992; 41: 1110-1114
        • Nègre-Salvayre AM
        • Pieraggi T
        • Mabile L
        • Salvayre R.
        Protective effect of 17β-estradiol against the cytotoxicity of minimally oxidized LDL to cultured bovine aortic endothelial cells.
        Atherosclerosis. 1993; 99: 207-217
        • Subbiah MTR
        • Kessel B
        • Agrawal M
        • Rajan R
        • Abplanalp W
        • Rymaszewski Z.
        Antioxidant potential of specific estrogens on lipid peroxidation.
        J Clin Endocrinol Metab. 1993; 77: 1095-1097
        • Zhu XD
        • Meekins D
        • Bonet B
        • Knopp RH.
        Effects of sex hormones on susceptibility of low density lipoprotein to copper mediated oxidative modification.
        Clin Res. 1993; 41 ([abstract]): 26A
        • Sack MN
        • Rader DJ
        • Cannon III., RO
        Oestrogen and inhibition of oxidation of low-density lipoproteins in postmenopausal women.
        Lancet. 1994; 343: 269-270
        • Hubel CA
        • McLaughlin MK
        • Evans RW
        • Hauth BA
        • Sims CJ
        • Roberts JM.
        Fasting serum triglycerides, free fatty acids, and malondialdehyde are increased in preeclampsia, are positively correlated, and decrease within 48 hours post partum.
        Am J Obstet Gynecol. 1996; 174: 975-982
        • Carone D
        • Loverro G
        • Greco P
        • Capuano P
        • Selvaggi L.
        Lipid peroxidation products and antioxidant enzymes in red blood cells during normal and diabetic pregnancy.
        Eur J Obstet Gynaecol. 1993; 51: 103-109
        • Wang Y
        • Walsh SW
        • Kay HH.
        Placental lipid peroxides and thromboxane are increased and prostacyclin is decreased in women with preeclampsia.
        Am J Obstet Gynecol. 1992; 167: 946-949
        • Boyd PA
        • Scott A.
        Quantitative structural studies on human placentas associated with pre-eclampsia, essential hypertension and intrauterine growth retardation.
        Br J Obstet Gynaecol. 1985; 92: 714-721
        • Driscoll SG.
        The pathology of pregnancy complicated by diabetes mellitus.
        Med Clin North Am. 1965; 49: 1053-1067
        • Naeye R.
        Effects of maternal cigarette smoking on the fetus and placenta.
        Br J Obstet Gynaecol. 1978; 85: 732-737
        • Bonet B
        • Chait A
        • Gown AM
        • Knopp RH.
        Metabolism of modified LDL by cultured human placental cells.
        Atherosclerosis. 1995; 112: 125-136
        • Lasunción MA
        • Bonet B
        • Knopp RH.
        Mechanism of the HDL2 stimulation of progesterone secretion in cultured placental trophoblast.
        J Lipid Res. 1991; 32: 1073-1087
        • Henriksen T
        • Evensen SA
        • Carlander B.
        Injury to human endothelial cells in culture induced by low density lipoproteins.
        Scand J Clin Lab Invest. 1979; 39: 361-368
        • Honjo H
        • Tanaka K
        • Yasuda J
        • Ohno Y
        • Kitawaki J
        • Naitoh K
        • et al.
        Serum estradiol 17-sulphate and lipid peroxides in late pregnancy.
        Acta Endocrinol. 1992; 126: 303-307
        • Jaffe RB.
        Endocrine physiology of the fetus and fetoplacental unit.
        in: 3rd ed. Endocrinology. Saunders, Philadelphia1991: 901-904
        • Tappel AL.
        Lipid peroxidation damage to cell components.
        Fed Proc. 1973; 32: 1870-1874