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Theriogenology2018; 122; 130-136; doi: 10.1016/j.theriogenology.2018.09.001

Changes in maternal pregnane concentrations in mares with experimentally-induced, ascending placentitis.

Abstract: The objectives of this study were to compare via liquid chromatography-tandem mass spectrometry (LC-MS/MS) progesterone (P4), 5α-dihydroprogesterone (DHP), allopregnanolone, 3β-hydroxy-5α-pregnan-20-one (3β5P), 20α-hydroxy-5α-pregnan-3-one (20α5P), 5α-pregnan-3β,20α-diol (βα-diol), and 5α-pregnan-3β,20β-diol (ββ-diol) concentrations in plasma of mares with experimentally-induced, ascending placentitis compared to gestationally age-matched control mares. Placentitis was induced via intracervical inoculation of Streptococcus equi spp. zooepidemicus between 260 and 280 days of gestation. Placentitis mares were subdivided into those which aborted in less than eight days (n = 6; acute) and those that aborted at ≥ 8 days after inoculation (n = 9; chronic). Ten pregnant mares at similar gestational ages served as healthy controls. Pregnanes were measured for days (-8), -6, -4, -3, -2, -1, and 0 days preceding abortion in the treated mares, and for the matched days of gestation in the control mares by LC-MS/MS and by immunoassay for immunoreactive (ir) P4. In mares with chronic placentitis, concentrations of DHP and its downstream metabolites (allopregnanolone, 3β5P, 20α5P, βα-diol) increased at 2-8 days prior to abortion compared to control mares. Of these pregnanes, 20α5P and βα-diol increased at eight days prior to abortion and demonstrated the largest increase (approximately 3 to 4×) in mares with chronic placentitis compared to control mares. Concentrations of P4 determined by LC-MS/MS were at or below the limit of detection (0.5 ng/mL) for control mares and did not increase significantly in mares with chronic placentitis. Immunoreactive-P4 was increased at two days prior to abortion in mares with chronic placentitis but was not different from controls in mares with acute placentitis. In mares with acute placentitis, concentrations of DHP, allopregnanolone, 3β5P, 20α5P, and βα-diol decreased within 0-3 days prior to abortion. In mares with chronic placentitis, the patterns of increased pregnanes metabolized by the placenta was similar to changes in maternal pregnanes noted in normal mares beyond Day 300 of gestation and likely represent the effects of fetal stress and adrenal activation on pregnane metabolism by the fetus and placenta. Decreases in these same pregnanes in mares with acute cases likely reflect extreme fetal or placental compromise.
Publication Date: 2018-09-07 PubMed ID: 30265893DOI: 10.1016/j.theriogenology.2018.09.001Google Scholar: Lookup
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  • Journal Article

Summary

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The study investigates the changes in concentrations of various pregnane compounds in the blood plasma of pregnant mares who have been experimentally induced with ascending placentitis. Through sophisticated chromatographic techniques, the researchers identify significant changes specific to the condition that could improve future diagnosis and understanding of the disease in horses.

Introduction to the Research

  • This research is centered around understanding the changes in the concentrations of several pregnanes (progesterone and other related hormones) in mares with experimentally-induced, ascending placentitis.
  • Ascending placentitis is a type of infection that moves up from the lower regions of the body and affects the placenta, and it was induced here using the bacteria Streptococcus equi spp. zooepidemicus.
  • Comparison was made to a control group of healthy pregnant mares at the same stage of pregnancy.
  • Two groups of mares with induced placentitis were studied: those that ended in premature births within eight days (acute) and those that gave birth after eight or more days (chronic).

Methodology

  • Advanced analytical methods were used to measure the concentrations of various pregnanes in the blood plasma of the mares for a set period before the act of abortion.
  • The concentrations of progesterone (P4), 5α-dihydroprogesterone (DHP), allopregnanolone, 3β-hydroxy-5α-pregnan-20-one (3β5P), 20α-hydroxy-5α-pregnan-3-one (20α5P), 5α-pregnan-3β,20α-diol (βα-diol), and 5α-pregnan-3β,20β-diol (ββ-diol) were measured.
  • These measurements were performed using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) and Immunoassay for immunoreactive P4.

Findings

  • In mares with chronic placentitis, concentrations of DHP and its downstream metabolites surged 2-8 days prior to abortion compared to control mares.
  • Particularly, 20α5P and βα-diol showed the highest increase (approximately 3 to 4 times) 8 days before abortion in mares with chronic placentitis compared to control mares.
  • In the case of mares with acute placentitis, concentrations of DHP, allopregnanolone, 3β5P, 20α5P, and βα-diol were observed to decrease within 0-3 days prior to abortion.
  • Progesterone concentrations did not show major fluctuations in mares with chronic placentitis and was detected at low concentrations in control mares’ samples.
  • However, in mares with chronic placentitis, Immunoreactive-P4 heightened two days before abortion.

Conclusions

  • The patterns of increased placental metabolized pregnanes in mares with chronic placentitis resembled the changes in maternal pregnanes found in normal mares at later stages of gestation, suggesting that these patterns could reflect fetal stress and adrenal activity affecting pregnane metabolism.
  • The decrease in these pregnanes in acute cases likely indicates severe fetal or placental compromise.
  • These findings provide a stepping stone towards a more comprehensive understanding of the patho-physiological changes in mares affected by ascending placentitis and could guide the development of more effective diagnostic tools for this condition in horses.

Cite This Article

APA
Wynn MAA, Ball BA, May J, Esteller-Vico A, Canisso I, Squires E, Troedsson M. (2018). Changes in maternal pregnane concentrations in mares with experimentally-induced, ascending placentitis. Theriogenology, 122, 130-136. https://doi.org/10.1016/j.theriogenology.2018.09.001

Publication

ISSN: 1879-3231
NlmUniqueID: 0421510
Country: United States
Language: English
Volume: 122
Pages: 130-136
PII: S0093-691X(18)30766-0

Researcher Affiliations

Wynn, Michelle A A
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, 40546, USA.
Ball, Barry A
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, 40546, USA. Electronic address: b.a.ball@uky.edu.
May, John
  • College of Engineering, University of Kentucky, Lexington, KY, 40546, USA.
Esteller-Vico, Alejandro
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, 40546, USA.
Canisso, Igor
  • Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL, 61802, USA.
Squires, Edward
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, 40546, USA.
Troedsson, Mats
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, 40546, USA.

MeSH Terms

  • Animals
  • Chromatography, Liquid / veterinary
  • Female
  • Horse Diseases / metabolism
  • Horse Diseases / microbiology
  • Horses
  • Placenta Diseases / metabolism
  • Placenta Diseases / microbiology
  • Placenta Diseases / veterinary
  • Pregnancy
  • Pregnanes / blood
  • Pregnanes / chemistry
  • Streptococcus equi
  • Tandem Mass Spectrometry / veterinary

Citations

This article has been cited 2 times.
  1. Aleman M, Chigerwe M, Varga A, Madigan JE. Steroid precursors, steroids, neuroactive steroids, and neurosteroids concentrations in serum and saliva of healthy neonatal heifer Holstein calves.. J Vet Intern Med 2020 Nov;34(6):2767-2775.
    doi: 10.1111/jvim.15957pubmed: 33201530google scholar: lookup
  2. Aleman M, McCue PM, Chigerwe M, Madigan JE. Plasma concentrations of steroid precursors, steroids, neuroactive steroids, and neurosteroids in healthy neonatal foals from birth to 7 days of age.. J Vet Intern Med 2019 Sep;33(5):2286-2293.
    doi: 10.1111/jvim.15618pubmed: 31489708google scholar: lookup