RT Journal Article
SR Electronic
T1 Exometabolomic analysis of decidualizing human endometrial stromal and perivascular cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.08.06.221119
DO 10.1101/2020.08.06.221119
A1 Sarah Harden
A1 Jieliang Zhou
A1 Maria Diniz-da-Costa
A1 Emma S. Lucas
A1 Liang Cui
A1 Keisuke Murakami
A1 Jinling Fang
A1 Qingfeng Chen
A1 Jan J Brosens
A1 Yie Hou Lee
YR 2020
UL http://biorxiv.org/content/early/2020/08/06/2020.08.06.221119.abstract
AB 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 signalling molecules. Here, we used liquid chromatography-mass spectrometry to characterise the dynamic changes in metabolite secretion (exometabolome) of primary PVC and EnSC decidualized over 8 days. 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 a conspicuous difference in xanthine secretion 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.Competing Interest StatementThe authors have declared no competing interest.ADAadenosine deaminase;ADKadenosine kinase;AICAR5-aminoimidazole-4-carboxamide ribonucleotide;DSCdecidual stromal cell;EnSCendometrial stromal cell;FCfold-change;HPRThypoxanthine-guanine phosphoribosyl-transferase;IDOindoleamine 2,3-dioxygenase;IGFBP1insulin-like growth factor binding portein-1;IMPinosine monophosphate;MACSmagnetic activated cell sorting;MICAMHC class I polypeptide-related sequence A;MPAmedroxyprogesterone acetate;MRMmultiple reaction monitoring;NKG2Dkiller group 2D receptor (NKG2D);P2Rpurinergic receptors;PGE2prostaglandin E2;PNPpurine nucleoside phosphorylase;PRLprolactin;PVCperivascular cells;ROSreactive oxygen species;SUSD2sushi domain containing 2;uNKuterine natural killer cells;XDH /XORxanthine dehydrogenase / xanthine oxidoreductase