The reduction in circulating levels of estrogen and progesterone in women with preeclampsia

Abstract

Abnormalities in the development of placental vasculature in early pregnancy and the failure of transformation of the spiral arteries are associated with the pathogenesis of preeclampsia. Sex hormones influence neovascularisation during pregnancy. However the profiling of estrogen and progesterone in preeclampsia is controversial. In this study we investigated the serum levels of estrogen and progesterone in women with preeclampsia. Blood samples were collected from 86 preeclamptic and 97 gestation-matched normotensive pregnancies. The levels of 17β-estradiol (E2), progesterone and 2-methoxyestradiol (2-ME) in serum were measured. In addition, the levels of E2 and progesterone in conditioned media from preeclamptic or normotensive term placental explant cultures or placental explants that had been treated with hydrogen peroxide (H₂O₂) were measured. The expression of estrogen receptors (ER) and progesterone receptors (PR) in preeclamptic and control placentae were measured by immunohistochemistry. The serum levels of E2, progesterone and 2-ME were significantly reduced in women with preeclampsia compared to controls. There was no difference in the serum levels of E2 and progesterone between severe and mild or between early-onset and late-onset preeclampsia as well as between preeclampsia with and without fetal growth restriction (FGR). The levels of E2 and progesterone in preeclamptic placental explants cultures were significantly lower than in normotensive term placental explant cultures. Treatment with H₂O₂ was found to be associated with a reduction in E2 production by the placenta. We demonstrated lower levels of estrogen in preeclampsia and speculate that this reduction may be due to the impairment of placental function in preeclampsia.

Keywords: Estrogen; Oxidative stress; Preeclampsia; Progesterone; Severity of preeclampsia; Time of onset of preeclampsia.