PMID- 34658363 OWN - NLM STAT- MEDLINE DCOM- 20211228 LR - 20211228 IS - 1479-6805 (Electronic) IS - 0022-0795 (Linking) VI - 252 IP - 1 DP - 2021 Nov 24 TI - Algorithms predicting gestational stage from the maternal steroid metabolome of mares. PG - 45-57 LID - 10.1530/JOE-21-0249 [doi] AB - Hormone secretion by the maternal ovaries, trophoblast/placenta and fetus occurs sequentially, creating distinct steroid metabolomic 'signatures' in systemic blood of pregnant mares that vary with gestational stage. Algorithms were developed to predict the gestational day (GD) from the maternal steroid metabolome (nine steroids; pregnenolone (P5), progesterone (P4), 5alpha-dihydroprogesterone (DHP), 17alpha-hydroxyprogesterone, allopregnanolone, 20alpha-hydroxy-DHP, 3beta,20alpha-dihydroxy-DHP, DHEA and androstenedione) determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) of eight thoroughbred mares sampled longitudinally throughout pregnancy. A physiologically based model was developed to infer rates of steroid secretion during chorionic gonadotropin secretion, the luteo-placental shift and by the equine feto-placenta unit, demonstrating more variability in P5 and DHP than P4. The average of four empirical models, using nine steroids to predict GD, was calibrated (five mares, R2 = 0.94, RMSE = 20 days) and validated (three mares, R2 = 0.84, RMSE = 32 days). Validation performance was improved using paired samples taken 14 or 30 days apart (RMSE = 29 and 19 days, respectively). A second validation used an independent dataset (single serum samples from 56 mixed breed mares, RMSE = 79 days) and an additional longitudinal subset from the same population sampled monthly throughout gestation (seven mares, RMSE = 42 days). Again, using paired samples improved model performance (RMSE = 32.5 days). Despite less predictive performance of the mixed breed than the thoroughbred datasets, these models demonstrate the feasibility and potential for using maternal steroid metabolomic algorithms to estimate the stage of gestation in pregnant mares and perhaps monitor fetal development. FAU - Shorten, Paul R AU - Shorten PR AD - AgResearch Ltd., Ruakura Research Centre, Hamilton, New Zealand. FAU - Legacki, Erin L AU - Legacki EL AD - Department of Population Health & Reproduction, School of Veterinary Medicine, University of California, Davis, California, USA. FAU - Chavatte-Palmer, Pascale AU - Chavatte-Palmer P AD - Universite Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, France. AD - Ecole Nationale Veterinaire d'Alfort, BREED, Maisons-Alfort, France. FAU - Conley, Alan J AU - Conley AJ AD - Department of Population Health & Reproduction, School of Veterinary Medicine, University of California, Davis, California, USA. LA - eng PT - Evaluation Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211124 PL - England TA - J Endocrinol JT - The Journal of endocrinology JID - 0375363 RN - 0 (Steroids) SB - IM MH - *Algorithms MH - Animals MH - Chromatography, Liquid/veterinary MH - Datasets as Topic MH - Feasibility Studies MH - Female MH - Gestational Age MH - Horses MH - Metabolome MH - Models, Theoretical MH - Pregnancy MH - Pregnancy Tests/methods/veterinary MH - *Pregnancy, Animal MH - *Prenatal Diagnosis/methods/veterinary MH - Steroids/analysis/*metabolism MH - Tandem Mass Spectrometry/methods/veterinary OTO - NOTNLM OT - algorithms OT - equine OT - fetal development OT - gestation OT - maternal blood OT - mathematical modeling OT - metabolome OT - steroid EDAT- 2021/10/19 06:00 MHDA- 2021/12/29 06:00 CRDT- 2021/10/18 08:45 PHST- 2021/10/06 00:00 [received] PHST- 2021/10/14 00:00 [accepted] PHST- 2021/10/19 06:00 [pubmed] PHST- 2021/12/29 06:00 [medline] PHST- 2021/10/18 08:45 [entrez] AID - JOE-21-0249.R1 [pii] AID - 10.1530/JOE-21-0249 [doi] PST - epublish SO - J Endocrinol. 2021 Nov 24;252(1):45-57. doi: 10.1530/JOE-21-0249.