Mapping the placenta’s hormone network

Pregnancy rewires a mother’s physiology through complex hormonal signaling, with steroid hormones playing a central role. Produced in the adrenal glands, ovaries and especially the placenta, these hormones shape both maternal and fetal health. Mapping their pathways is key to understanding normal pregnancy and complications such as preterm birth or developmental disorders.

In a recent study published in Molecular & Cellular Proteomics, Christiane Albrecht, from the University of Bern, Rona Karahoda, from Charles University and colleagues profiled 51 steroids by analyzing maternal blood, newborn blood and placental tissue. Using liquid chromatography–mass spectrometry, LC-MS, the researchers measured both classic steroid hormones and a newer class known as 11-oxygenated, or 11-oxy, steroids. The group has explored this complex hormonal landscape by studying samples from 37 healthy pregnancies.

“Steroid pathways are notoriously complex, but by applying a more advanced analytical technique, we were able to profile a much broader spectrum of hormones. This revealed compounds that had previously gone undetected in pregnancy,” Karahoda said.

Although the placenta is not usually considered an androgen-producing organ, this study confirmed the presence of 11-oxy androgens and revealed that keto-steroids are also highly abundant. These findings suggest that the enzyme 11βHSD2 — best known for inactivating stress hormones — may play a broader role in placental steroid metabolism than previously appreciated.

“These results broaden our view of the enzyme’s role in the placenta,” Karahoda said. “They suggest that the placenta not only modulates glucocorticoids but also processes novel androgens and progesterones.

“Although we focused on healthy term pregnancies in this study, the next step would definitely be to look at conditions such as preeclampsia or fetal growth restriction to see how steroid metabolism, and particularly enzymes like 11βHSD2, are altered,” Karahoda said.

Redefining placental steroidogenesis could shed light on fetal programming and complications in pregnancy and provide a more comprehensive understanding of how placental steroid pathways influence both maternal and offspring health across the lifespan.