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The Journal of endocrinology2021; 252(1); 45-57; doi: 10.1530/JOE-21-0249

Algorithms predicting gestational stage from the maternal steroid metabolome of mares.

Abstract: 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), 5α-dihydroprogesterone (DHP), 17α-hydroxyprogesterone, allopregnanolone, 20α-hydroxy-DHP, 3β,20α-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.
Publication Date: 2021-11-24 PubMed ID: 34658363DOI: 10.1530/JOE-21-0249Google Scholar: Lookup
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  • Evaluation Study
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research paper involves devising algorithms that can predict the gestational day in pregnant horses (mares) through analysis of the maternal steroid metabolome – the range of steroid hormones in the mare’s blood. Hormone secretion patterns in these animals change throughout pregnancy, creating signature metabolome profiles that can be used to estimate the gestational timeline in mares by measuring nine specific steroids.

Study Methodology

  • Hormone measurements were done using liquid chromatography-tandem mass spectrometry (LC-MS/MS) on blood samples obtained from eight thoroughbred mares throughout their pregnancies.
  • A physiologically based model was created to estimate rates of steroid secretion during three distinct phases of pregnancy – chorionic gonadotropin secretion, the luteo-placental shift, and operation of the equine feto-placenta unit. The researchers noticed high variability in two of the nine hormones (pregnenolone (P5) and 5α-dihydroprogesterone (DHP)) compared to the others.

Model Calibration and Validation

  • The researchers formulated four empirical models using the nine specific steroids to predict gestational days, pooling the average results as a calibrated model.
  • The model’s accuracy was tested (calibrated) on five mares, producing a highly satisfactory match (R2 = 0.94) with an average error of 20 days.
  • For further reliability, the model was validated on three other mares, yielding a reasonably accurate match (R2 = 0.84) with an average error of 32 days.
  • Model performance improved when samples taken 14 or 30 days apart were compared, with errors reduced to 29 and 19 days, respectively.

Second Round of Validation

  • A second test phase involved another validation run using data from 56 different ‘mixed breed’ mares (not thoroughbreds), with a higher error margin of 79 days.
  • Yet another set of seven mares from amongst these were sampled regularly for data, averaging an error of 42 days.
  • Here too, using paired samples improved performance, reducing the error margin to around 32.5 days.

Conclusion

  • The study concludes that despite the higher error rates for mixed breed as compared to thoroughbreads, the models do show promise in predicting the gestational stage in pregnant mares using maternal steroid metabolomic profiles.
  • Not only can this be used to track the gestational day, it can also potentially provide valuable insight about fetal development.

Cite This Article

APA
Shorten PR, Legacki EL, Chavatte-Palmer P, Conley AJ. (2021). Algorithms predicting gestational stage from the maternal steroid metabolome of mares. J Endocrinol, 252(1), 45-57. https://doi.org/10.1530/JOE-21-0249

Publication

ISSN: 1479-6805
NlmUniqueID: 0375363
Country: England
Language: English
Volume: 252
Issue: 1
Pages: 45-57

Researcher Affiliations

Shorten, Paul R
  • AgResearch Ltd., Ruakura Research Centre, Hamilton, New Zealand.
Legacki, Erin L
  • Department of Population Health & Reproduction, School of Veterinary Medicine, University of California, Davis, California, USA.
Chavatte-Palmer, Pascale
  • Université Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, France.
  • Ecole Nationale Vétérinaire d'Alfort, BREED, Maisons-Alfort, France.
Conley, Alan J
  • Department of Population Health & Reproduction, School of Veterinary Medicine, University of California, Davis, California, USA.

MeSH Terms

  • Algorithms
  • Animals
  • Chromatography, Liquid / veterinary
  • Datasets as Topic
  • Feasibility Studies
  • Female
  • Gestational Age
  • Horses
  • Metabolome
  • Models, Theoretical
  • Pregnancy
  • Pregnancy Tests / methods
  • Pregnancy Tests / veterinary
  • Pregnancy, Animal
  • Prenatal Diagnosis / methods
  • Prenatal Diagnosis / veterinary
  • Steroids / analysis
  • Steroids / metabolism
  • Tandem Mass Spectrometry / methods
  • Tandem Mass Spectrometry / veterinary

Citations

This article has been cited 2 times.
  1. Denham SG, Simpson JP, Diez F, Lee P, Kyle C, Morgan R, Homer NZ. A practical approach to supported liquid extraction and measurement of 18 steroids in plasma and serum by targeted liquid chromatography tandem mass spectrometry. MethodsX 2024 Jun;12:102728.
    doi: 10.1016/j.mex.2024.102728pubmed: 38948242google scholar: lookup
  2. Rabaglino MB, Sánchez JM, McDonald M, O'Callaghan E, Lonergan P. Maternal blood transcriptome as a sensor of fetal organ maturation at the end of organogenesis in cattle†. Biol Reprod 2023 Nov 15;109(5):749-758.
    doi: 10.1093/biolre/ioad103pubmed: 37658765google scholar: lookup