F Braun1, A K Hardt1, L Ehrlich1, D M Sloboda2, J R G Challis3, A Plagemann1, W Henrich1, T Braun4. 1. Department of Obstetrics and Division of 'Experimental Obstetrics̔, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany. 2. Department of Biochemistry and Biomedical Sciences, Obstetrics & Gynecology and Pediatrics, Farncombe Family Digestive Health Research Institute, McMaster University, Main Street West, Ontario L8S4L8, Hamilton, 1280, Canada. 3. Department of Physiology and Obstetrics and Gynecology, University of Toronto King's College Circle, Ontario M5S 1A8, Toronto, Canada; Faculty of Health Sciences, Simon Fraser University, University Drive, 8888, B.C, V5A 1S6, Burnaby, Canada. 4. Department of Obstetrics and Division of 'Experimental Obstetrics̔, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany. Electronic address: thorsten.braun@charite.de.
Abstract
INTRODUCTION: We have previously shown that even a single course of antenatal betamethasone (BET) as an inductor for lung maturity reduces birth weight and head circumference. Moreover, animal studies link BET administration to alterations of the hypothalamic-pituitary-adrenal-gland-axis (HPA). The unhindered development of the fetal HPA axis is dependent on the function and activity of 11β-hydroxysteroiddehydrogenase type 2 (11β-HSD2), a transplacental cortisol barrier. Therefore, we investigated the effects of BET on this transplacental barrier and fetal growth. METHODS: Pregnant women treated with a single course of BET between 23 + 5 to 34 + 0 weeks of gestation were compared to gestational-age-matched controls. Placental size and neonatal anthropometrics were taken. Cortisol and ACTH levels were measured in maternal and umbilical cord blood samples. Placental 11β-hydroxysteroiddehydrogenase type 1 (11β-HSD1) protein levels and 11β-HSD2 protein and activity levels were determined. Parameters were analyzed independent of sex, and in subgroups divided by gender and gestational age. RESULTS: In term born females, BET administration was associated with reduced head circumference and decreased 11β-HSD2 protein levels and enzyme activity. Males treated with BET, especially those born prematurely, showed increased 11β-HSD2 protein levels. CONCLUSION: A single course of BET alters placental glucocorticoid metabolism in a sex-specific manner. Decreased 11β-HSD2 levels in term born females may lead to an increased placental transfer of maternal cortisol and therefore result in a reduced head circumference and a higher risk for altered stress response in adulthood. Further research is needed to conclude the significance of increased 11β-HSD2 levels in males.
INTRODUCTION: We have previously shown that even a single course of antenatal betamethasone (BET) as an inductor for lung maturity reduces birth weight and head circumference. Moreover, animal studies link BET administration to alterations of the hypothalamic-pituitary-adrenal-gland-axis (HPA). The unhindered development of the fetal HPA axis is dependent on the function and activity of 11β-hydroxysteroiddehydrogenase type 2 (11β-HSD2), a transplacental cortisol barrier. Therefore, we investigated the effects of BET on this transplacental barrier and fetal growth. METHODS: Pregnant women treated with a single course of BET between 23 + 5 to 34 + 0 weeks of gestation were compared to gestational-age-matched controls. Placental size and neonatal anthropometrics were taken. Cortisol and ACTH levels were measured in maternal and umbilical cord blood samples. Placental 11β-hydroxysteroiddehydrogenase type 1 (11β-HSD1) protein levels and 11β-HSD2 protein and activity levels were determined. Parameters were analyzed independent of sex, and in subgroups divided by gender and gestational age. RESULTS: In term born females, BET administration was associated with reduced head circumference and decreased 11β-HSD2 protein levels and enzyme activity. Males treated with BET, especially those born prematurely, showed increased 11β-HSD2 protein levels. CONCLUSION: A single course of BET alters placental glucocorticoid metabolism in a sex-specific manner. Decreased 11β-HSD2 levels in term born females may lead to an increased placental transfer of maternal cortisol and therefore result in a reduced head circumference and a higher risk for altered stress response in adulthood. Further research is needed to conclude the significance of increased 11β-HSD2 levels in males.
Authors: Elisabeth B Binder; Thorsten Braun; Sonja Entringer; Darina Czamara; Linda Dieckmann; Simone Röh; Sarah Kraemer; Rebecca C Rancourt; Sara Sammallahti; Eero Kajantie; Hannele Laivuori; Johan G Eriksson; Katri Räikkönen; Wolfgang Henrich; Andreas Plagemann Journal: Clin Epigenetics Date: 2021-08-26 Impact factor: 6.551
Authors: Elisabeth B Binder; Darina Czamara; Linda Dieckmann; Cristiana Cruceanu; Marius Lahti-Pulkkinen; Jari Lahti; Tuomas Kvist; Hannele Laivuori; Sara Sammallahti; Pia M Villa; Sanna Suomalainen-König; Rebecca C Rancourt; Andreas Plagemann; Wolfgang Henrich; Johan G Eriksson; Eero Kajantie; Sonja Entringer; Thorsten Braun; Katri Räikkönen Journal: Cell Mol Life Sci Date: 2022-02-03 Impact factor: 9.261