Progestin withdrawal at parturition in the mare.

The research explores the role of progestin in horse pregnancies, and how its withdrawal before birth might trigger labor. It further investigates the levels of various pregnanes, including progesterone, in mares before foaling, and their potential biological roles in the absence of dihydroprogesterone (DHP).

Research Methodology

• The study concentrated on mares for ten days before birth and was aimed at monitoring the systemic pregnane levels. These included 5α-dihydroprogesterone (DHP), allopregnanolone, pregnenolone, 20α-hydroxy-5α-dihydroprogesterone (20αDHP), and 5α-pregnane-3β.
• Researchers used liquid chromatography-mass spectrometry to monitor these levels. The same technique was also performed for monitoring progesterone levels.
• In order to evaluate the biopotency of these metabolites, luciferase reporter assays were deployed. As part of this process, Chinese hamster ovarian cells, which were stably transfected to express equine progesterone receptor (ePGR), were further transfected with an MMTV-luciferase expression plasmid.
• These cells were then exposed to increasing concentrations (ranging from 0-100nM) of progesterone, 20αDHP, and 3α,20βDHP.

Research Findings

• They found that among periparturient mares, duration before parturition witnessed a significant decline in all pregnanes with an average decrease by 50% from peaks detected before birth to one day before birth.
• The levels of 3α,20βDHP and 20αDHP were found to be the highest, followed by DHP and allopregnanolone. The lowest were pregnenolone and progesterone.
• Examination of the maximum activation of ePGR by progesterone revealed that it occurred at 30nM. Further, 20αDHP and 3α,20βDHP were discovered to be less biopotent compared to progesterone.
• Despite this, the researchers noted that prepartum concentrations of both 20αDHP and 3α,20βDHP were ample to trigger significant ePGR activation.

Conclusion

• The study concluded that progestogenic backing of pregnancy starts reducing around three to five days before birth.
• The authors concluded that the major progestin at peak prepartum concentration is DHP but in its absence other pregnanes like 20αDHP play a significant physiological role.
• Finally, they ascertained that the progestin withdrawal prompting parturition in mares involves the halt of pregnane synthesis by the placenta.