Exometabolomic Analysis of Decidualizing Human Endometrial Stromal and Perivascular Cells

Abstract

Differentiation of endometrial fibroblasts into specialized decidual cells controls embryo implantation and transforms the cycling endometrium into a semi-permanent, immune-protective matrix that accommodates the placenta throughout pregnancy. This process starts during the midluteal phase of the menstrual cycle with decidual transformation of perivascular cells (PVC) surrounding the terminal spiral arterioles and endometrial stromal cells (EnSC) underlying the luminal epithelium. Decidualization involves extensive cellular reprogramming and acquisition of a secretory phenotype, essential for coordinated placental trophoblast invasion. Secreted metabolites are an emerging class of signaling molecules, collectively known as the exometabolome. Here, we used liquid chromatography-mass spectrometry to characterize and analyze time-resolved changes in metabolite secretion (exometabolome) of primary PVC and EnSC decidualized over 8 days. PVC were isolated using positive selection of the cell surface marker SUSD2. We identified 79 annotated metabolites differentially secreted upon decidualization, including prostaglandin, sphingolipid, and hyaluronic acid metabolites. Secreted metabolites encompassed 21 metabolic pathways, most prominently glycerolipid and pyrimidine metabolism. Although temporal exometabolome changes were comparable between decidualizing PVC and EnSC, 32 metabolites were differentially secreted across the decidualization time-course. Further, targeted metabolomics demonstrated significant differences in secretion of purine pathway metabolites between decidualized PVC and EnSC. Taken together, our findings indicate that the metabolic footprints generated by different decidual subpopulations encode spatiotemporal information that may be important for optimal embryo implantation.

LC-MS Analysis Revealed the Significantly Different Metabolic Profiles in Spent Culture Media of Human Embryos with Distinct Morphology, Karyotype and Implantation Outcomes

“…et al investigated the exometabolome of decidualizing human stromal cells in culture and concluded that the metabolic footprints of cellular microenvironment generated by different decidual subpopulations encode spatiotemporal information that may be important for their differentiation and optimal embryo implantation. It has been shown that in all investigated timepoints of decidualization the most enriched metabolic pathways of stromal cells exometabolome are phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine, and isoleucine biosynthesis, glycerophospholipid metabolism, linoleic acid metabolism, purine and pyrimidine metabolism [ 72 ]. It is interesting to note, that the similar pathways were enriched after analysis of day 5 human embryo exometabolome in our study.…”

Multiomics Studies Investigating Recurrent Pregnancy Loss: An Effective Tool for Mechanism Exploration

“…Another study by Harden et al. showed significant differences in endometrial metabolic profiles between decidualized and nondecidualized endometrium, which may be essential for successful embryo implantation ( 46 ).…”

The ratio of nicotinic acid to nicotinamide as a microbial biomarker for assessing cell therapy product sterility

“…The samples were analyzed using an Agilent 1290 ultrahigh pressure liquid chromatography system (Agilent, Waldbronn, Germany) equipped with a 6550 iFunnel Q-TOF mass detector managed by a MassHunter Workstation, as previously described. 48,49 A Waters ACQUITY UPLC HSS T3 (2.1 Â 100 mm, 1.8 mm; Waters, Milford, MA, USA) column was used with a Waters ACQUITY HSS T3 1.8 mM VanGuard guard column. The column temperature was 50 C. The separation was performed under a gradient elution which involved a mobile phase consisting of (A) 0.1% formic acid in water and (B) 0.1% formic acid in methanol.…”