Recent advances in analytical methods have revolutionized our understanding of steroid biochemistry. The emergence of novel steroids such as 11-oxy androgens and 11-oxy progesterones has necessitated a reevaluation of steroid biosynthesis and metabolism within the maternal-placental-fetal unit. In this study, we employed a validated liquid chromatography high-resolution mass spectrometry method to quantify 51 steroids in paired maternal serum, neonatal serum, and placenta samples from 37 healthy pregnancies. Additionally, we characterized steroid release in various placental models, including human placenta perfusion, explants, and primary trophoblast cells isolated from human term placenta. Our findings emphasize the predominance of keto derivatives of androgens in the placenta compared to hydroxylated forms, which are dominant in maternal serum and neonatal serum. We also observed high levels of classic and novel progesterones in the placenta and across all models, with significant release on the maternal side. These results suggest that the placenta possesses an active enzymatic machinery capable of producing and metabolizing novel progesterones. Furthermore, we demonstrated that the catalytic activity of 11β-hydroxysteroid dehydrogenase type 2 extends beyond cortisol regulation to hydroxylated androgens, highlighting its significance in the broader context of steroid metabolism within the maternal-placental-fetal unit. These findings contribute to our understanding of placental physiology and impact on fetal development.

• Keywords
• androgen, placenta, pregnancy, progesterone, steroidogenesis,
• MeSH
• 11-beta-Hydroxysteroid Dehydrogenase Type 2 metabolism   MeSH
• Androgens metabolism   blood   MeSH
• Models, Biological MeSH
• Chromatography, Liquid MeSH
• Adult MeSH
• Humans MeSH
• Maternal-Fetal Exchange MeSH
• Infant, Newborn MeSH
• Placenta * metabolism   MeSH
• Steroids * metabolism   blood   MeSH
• Pregnancy MeSH
• Trophoblasts metabolism   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• 11-beta-Hydroxysteroid Dehydrogenase Type 2 MeSH
• Androgens MeSH
• Steroids * MeSH

Gestational diabetes mellitus (GDM) is a complication in pregnancy, but studies focused on the steroidome in patients with GDM are not available in the public domain. This article evaluates the steroidome in GDM+ and GDM- women and its changes from 24 weeks (± of gestation) to labor. The study included GDM+ (n = 44) and GDM- women (n = 33), in weeks 24-28, 30-36 of gestation and at labor and mixed umbilical blood after delivery. Steroidomic data (101 steroids quantified by GC-MS/MS) support the concept that the increasing diabetogenic effects with the approaching term are associated with mounting progesterone levels. The GDM+ group showed lower levels of testosterone (due to reduced AKR1C3 activity), estradiol (due to a shift from the HSD17B1 towards HSD17B2 activity), 7-oxygenated androgens (competing with cortisone for HSD11B1 and shifting the balance from diabetogenic cortisol towards the inactive cortisone), reduced activities of SRD5As, and CYP17A1 in the hydroxylase but higher CYP17A1 activity in the lyase step. With the approaching term, the authors found rising activities of CYP3A7, AKR1C1, CYP17A1 in its hydroxylase step, but a decline in its lyase step, rising conjugation of neuroinhibitory and pregnancy-stabilizing steroids and weakening AKR1D1 activity.

• Keywords
• gas chromatography-tandem mass spectrometry, gestational age, gestational diabetes mellitus, immunoprotective steroids, maternal blood, mixed cord blood, neuroactive steroids, steroidome,
• MeSH
• 20-Hydroxysteroid Dehydrogenases metabolism   MeSH
• Chromatography, Gas MeSH
• Cytochrome P-450 CYP3A metabolism   MeSH
• Pregnancy Trimester, Second metabolism   MeSH
• Diabetes, Gestational metabolism   MeSH
• Humans MeSH
• Metabolomics methods   MeSH
• Oxidoreductases metabolism   MeSH
• Steroid 17-alpha-Hydroxylase metabolism   MeSH
• Steroids analysis   MeSH
• Tandem Mass Spectrometry MeSH
• Pregnancy MeSH
• Check Tag
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• 20-Hydroxysteroid Dehydrogenases MeSH
• 3 alpha-beta, 20 beta-hydroxysteroid dehydrogenase MeSH Browser
• 3-oxo-5 beta-steroid delta 4-dehydrogenase MeSH Browser
• CYP17A1 protein, human MeSH Browser
• CYP3A7 protein, human MeSH Browser
• Cytochrome P-450 CYP3A MeSH
• Oxidoreductases MeSH
• Steroid 17-alpha-Hydroxylase MeSH
• Steroids MeSH