Thomas L.C. Woo1, Michelle Broekhuizen1,2,3, Madhavi S. Harhangi1,3, Sjoerd A.A. van den Berg4, A.H. Jan Danser1, Koen Verdonk1, Irwin Reiss3, Tim I.M. Korevaar1
(1) Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
(2) Department of Experimental Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands.
(3) Department of Neonatology, Erasmus Medical Center, Rotterdam, The Netherlands.
(4) Department of Clinical Chemistry, Erasmus Medical Center, Rotterdam, The Netherlands.
The placenta is a major endocrine organ that is crucial for fetal development and coordinates maternal physiology. However, it is still being debated which hormones are synthesized by the placenta.
Here, we studied this using an ex vivo dual-sided human placenta perfusion model. Maternal- and fetal-compartment perfusates were collected from three healthy term placentas at 0, 60, 120, and 180 minutes and a panel of hormones was analyzed using UPLC-MS/MS or immunoassay. Average production/release was calculated between 60 – 180 minutes omitting hormones that were present in remaining blood.
Hormone production detected in both the maternal and fetal circulations includes 11-deoxycorticosterone (fetal: 0.56, maternal: 0.49 nmol/h), 11-deoxycortisol (fetal: 0.90, maternal: 1.84 nmol/h) and 17-hydroxyprogesterone (fetal: 0.75, maternal: 0.74 nmol/h). Progesterone was above the detection limit in all maternal and fetal samples from 60 minutes onwards (>50 nmol/L). ACTH (2.9 pmol/h), cortisol (0.9 nmol/h), prolactin (0.1 U/h), leptin (3.0 μg/h), were only detected maternally and not fetally. Oestradiol and copeptin were not produced/released throughout the experiment. Hormones below the detection limit maternally and fetally included: IGF-1 (<1.3 nmol/L), C-peptide (<0.016 nmol/L), androstenedione (<0.1 nmol/L), DHEA (<3.6 nmol/L), testosterone (<0.06 nmol/L), dihydrotestosterone (<0.2 nmol/L), corticosterone (<0.8 nmol/L) and 11-oxy androgens (<0.3 nmol/L).
We provide quantitative evidence of clinically relevant production of ACTH, cortisol, prolactin, leptin, 11-deoxycorticosterone, 11-deoxycortisol and 17-hydroxyprogesterone by the human placenta. These findings demonstrate the ex vivo dual-sided placenta perfusion model as a powerful tool for comprehensive profiling of real-time placental hormone production.