From Pregnancy to Preeclampsia: A Key Role for Estrogens.
Preeclampsia (PE) results in placental dysfunction and is one of the primary causes of maternal and fetal mortality and morbidity. During pregnancy, estrogen is produced primarily in the placenta by conversion of androgen precursors originating from maternal and fetal adrenal glands. These processes lead to increased plasma estrogen concentrations compared with levels in nonpregnant women. Aberrant production of estrogens could play a key role in PE symptoms because they are exclusively produced by the placenta and they promote angiogenesis and vasodilation. Previous assessments of estrogen synthesis during PE yielded conflicting results, possibly because of the lack of specificity of the assays. However, with the introduction of reliable analytical protocols using liquid chromatography/mass spectrometry or gas chromatography/mass spectrometry, more recent studies suggest a marked decrease in estradiol levels in PE. The aim of this review is to summarize current knowledge of estrogen synthesis, regulation in the placenta, and biological effects during pregnancy and PE. Moreover, this review highlights the links among the occurrence of PE, estrogen biosynthesis, angiogenic factors, and cardiovascular risk factors. A close link between estrogen dysregulation and PE occurrence might validate estrogen levels as a biomarker but could also reveal a potential approach for prevention or cure of PE.
Department of Gynecology and Obstetrics of University Hospital of Geneva, 1205, Genève, Switzerland.|U1195, INSERM and University Paris Sud, 94276 Kremlin Bicêtre, France.
Nadia
N
Berkane
U1195, INSERM and University Paris Sud, 94276 Kremlin Bicêtre, France.
Philippe
P
Liere
U1195, INSERM and University Paris Sud, 94276 Kremlin Bicêtre, France.
Jean-Paul
JP
Oudinet
Department of Nephrology, Tenon Hospital, APHP, 75020 Paris, France.|University of Pierre and Marie Curie, Sorbonne University, Paris 06, 75005 Paris, France.|Unité Mixte de Recherche Scientifique 1155, F-75020 Paris, France.
Alexandre
A
Hertig
University of Pierre and Marie Curie, Sorbonne University, Paris 06, 75005 Paris, France.|Department of Biochemistry and Hormonology, Tenon Hospital, APHP, F-75020 Paris, France.
Guillaume
G
Lefèvre
Department of Gynecology and Obstetrics of University Hospital of Geneva, 1205, Genève, Switzerland.
Nicola
N
Pluchino
U1195, INSERM and University Paris Sud, 94276 Kremlin Bicêtre, France.
Michael
M
Schumacher
University of Pierre and Marie Curie, Sorbonne University, Paris 06, 75005 Paris, France.|Department of Obstetrics, Gynecology and Reproductive Medicine, Tenon Hospital, APHP, F-75020 Paris, France.|INSERM, UMR-S938, Centre de Recherche Saint-Antoine, F-75012 Paris, France.
Nathalie
N
Chabbert-Buffet
D000818:Animals; D004967:Estrogens / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D010922:Placenta Diseases / Q000378:metabolism* / Q000503:physiopathology; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000503:physiopathology; D011247:Pregnancy
D004967:Estrogens