Nadia Berkane1, Philippe Liere2, Guillaume Lefevre3, Nadia Alfaidy4, Roland Abi Nahed4, Jessica Vincent5, Jean-Paul Oudinet2, Antoine Pianos2, Annie Cambourg2, Patrick Rozenberg6, Pierre Galichon7, Alexandra Rousseau8, Tabassome Simon8, Michael Schumacher2, Nathalie Chabbert-Buffet9, Alexandre Hertig10. 1. Department of Gynecology and Obstetrics and Reproductive Medicine, Assistance Publique des Hôpitaux de Paris (APHP), Sorbonne University, Paris, France; Department of Gynecology and Obstetrics, University of Geneva Hospitals (HUG), Geneva, Switzerland. 2. U1195 INSERM and University Paris-Sud, Kremlin-Bicêtre, France. 3. Department of Biochemistry and Hormonology, Assistance Publique des Hôpitaux de Paris (APHP), Sorbonne University, Paris, France. 4. U1036 INSERM, Biosciences and Biotechnology Institute, Grenoble, France. 5. Department of Gynecology and Obstetrics, University of Geneva Hospitals (HUG), Geneva, Switzerland. 6. Department of Obstetrics and Gynecology, Poissy-Saint Germain Hospital, Poissy, France. 7. Department of Nephrology, Assistance Publique des Hôpitaux de Paris (APHP), Sorbonne University, Tenon Hospital, Paris, France. 8. Department of Clinical Research Center-Est (URCEST), St. Antoine Hospital, Paris, France. 9. Department of Gynecology and Obstetrics and Reproductive Medicine, Assistance Publique des Hôpitaux de Paris (APHP), Sorbonne University, Paris, France. 10. Department of Nephrology, Assistance Publique des Hôpitaux de Paris (APHP), Sorbonne University, Tenon Hospital, Paris, France. Electronic address: alexandre.hertig@aphp.fr.
Abstract
INTRODUCTION: Estrogens and progesterone play critical roles in angiogenesis and vasodilation. Moreover, placental aromatase deficiency is detected in women with preeclampsia (PE) at delivery. We hypothesized that abnormal steroidogenesis occurs much earlier than typical PE diagnosis. Thus, we investigated whether the circulating steroid profile was already disturbed at 24-29 weeks of gestation in women with subsequent PE, and compared the profile with that of women with "placental" small gestational age (SGA) without PE. METHODS: We selected nulliparous women (n = 90) from the MOMA trial, including women with PE (n = 25), SGA (n = 25), and controls (NP; n = 40), for plasma steroid profiling by gas chromatography/mass spectrometry and to measure placental growth factor and soluble fms-like tyrosine kinase-1. Placental aromatase expression was evaluated in a new set of women. RESULTS: Compared with that of controls, the women with PE had a significantly lower estrone/androstenedione ratio, and exhibited a decreasing trend for estradiol and estrone levels. Lower estriol levels were observed in the SGA group compared to the NP group. Compared with that of controls, the women with PE and SGA had significantly higher levels of 20α-dihydroprogesterone (20α-DHP) and 20α-DHP/progesterone ratios. Pregnenolone sulfate levels were lower in the PE group than in the NP and SGA groups. Decreased expression of aromatase was observed in the PE group compared to the control group. DISCUSSION: Preeclampsia appears to be characterized by specific steroidogenesis dysregulation long before PE diagnosis, highlighting potential new biomarkers of PE.
INTRODUCTION: Estrogens and progesterone play critical roles in angiogenesis and vasodilation. Moreover, placental aromatase deficiency is detected in women with preeclampsia (PE) at delivery. We hypothesized that abnormal steroidogenesis occurs much earlier than typical PE diagnosis. Thus, we investigated whether the circulating steroid profile was already disturbed at 24-29 weeks of gestation in women with subsequent PE, and compared the profile with that of women with "placental" small gestational age (SGA) without PE. METHODS: We selected nulliparous women (n = 90) from the MOMA trial, including women with PE (n = 25), SGA (n = 25), and controls (NP; n = 40), for plasma steroid profiling by gas chromatography/mass spectrometry and to measure placental growth factor and soluble fms-like tyrosine kinase-1. Placental aromatase expression was evaluated in a new set of women. RESULTS: Compared with that of controls, the women with PE had a significantly lower estrone/androstenedione ratio, and exhibited a decreasing trend for estradiol and estrone levels. Lower estriol levels were observed in the SGA group compared to the NP group. Compared with that of controls, the women with PE and SGA had significantly higher levels of 20α-dihydroprogesterone (20α-DHP) and 20α-DHP/progesterone ratios. Pregnenolone sulfate levels were lower in the PE group than in the NP and SGA groups. Decreased expression of aromatase was observed in the PE group compared to the control group. DISCUSSION: Preeclampsia appears to be characterized by specific steroidogenesis dysregulation long before PE diagnosis, highlighting potential new biomarkers of PE.
Authors: Gaby A M Eliesen; Hedwig van Hove; Maartje H Meijer; Petra H H van den Broek; Jeanne Pertijs; Nel Roeleveld; Joris van Drongelen; Frans G M Russel; Rick Greupink Journal: Arch Toxicol Date: 2020-10-20 Impact factor: 5.153