Equine placentitis is associated with a downregulation in myometrial progestin signaling†.

The study investigates the role of progestins and progesterone receptor signaling pathways during equine placentitis, a reproductive disorder in horses. The findings indicate that placentitis in mares leads to a reduction in progestin signalling and activation of inflammatory response in the myometrium.

Research Methodology

The study involved an experimental group of mares diagnosed with equine placentitis (n = 6) and a control group (n = 4) of healthy, gestationally matched mares.

• Placentitis was induced in the experimental group through intracervical inoculation with Streptococcus equi ssp zooepidemicus around 290 days of gestation.
• After euthanizing the mares, myometrial samples were collected from two different regions for both groups. The first region was parallel to the active placentitis lesion with placental separation in the placentitis group (P1) or the caudal pole of the placenta in the control group (C1). The second region was parallel to the apparently healthy placenta without separation in the placentitis group (P2) or the uterine body in the control group (C2).

Key Findings

The research discovered a notable change in the expression of two genes – SRD5A1 and AKR1C23.

• These genes encode for P4 metabolizing enzymes and were found to be downregulated in region P1 in the placentitis group in comparison to regions C1, C2, and P2.
• Simultaneously, there was a decrease in certain progestins (5αDHP, allopregnanolone (3αDHP), and 20αDHP) within the region P1, compared to regions C1 and other regions.

The research also found a downregulation of the progesterone receptor (PR) expression in the myometrium, particularly in region P1, compared to regions C1 and P2.

• This downregulation was accompanied by increased inflammatory reactions, as indicated by the upregulation of inflammatory cytokines (IL-1β and IL-8) in region P1, compared to regions C1, C2, and P2. This was also evidenced by an increased number of tissue leukocytes in P1 compared to C1.

Conclusions

Based on these findings, the study concludes that equine placentitis is linked to a localized decrease of progestins and a decline in the PR in the myometrium. This is coupled with an upregulation of inflammatory cytokines, leading to myometrial activation. The findings suggest a potential pathway through which equine placentitis progresses and gives insights into possible therapeutic interventions.