Tumor necrosis factor signaling during equine placental infection leads to pro-apoptotic and necroptotic outcomes.

The research investigates on how tumor necrosis factor (TNF), a protein involved in cell signaling, operates during a placental infection in horses, leading to disruptive cell death and potential abortion.

Introduction

• The paper looks into Ascending placentitis, a chief cause of abortion in horses. A vital protein regulator for this disease is tumor necrosis factor (TNF), although there’s limited understanding on its role in perpetuating the disease.
• This study utilizes RNA sequencing on healthy and diseased tissue samples to discern the behavior of TNF and its receptors (TNFR-1 and TNFR-2) during disease progression.

Methodology

• RNA sequencing is executed on tissue samples collected from healthy pregnant horses at different gestational phases, postpartum tissues, as well as tissues during non-reproductive cycles (diestrus).
• Disease is induced in other mares through the introduction of infection-causing bacteria, Streptococcus equi subspecies zooepidemicus, directly into the cervix.
• Tissues and blood samples are taken following disease induction to study changes in the concentration and actions of TNF and its receptors.
• Immunohistological chemistry (IHC), a microscopic study technique, is also undertaken to confirm the locations of TNF receptors in the tissue samples.

Results

• In healthy pregnancies, TNFR-1 is the more common receptor in play.
• Following disease induction, TNF concentration increases in maternal blood, however, its expression remained constant at tissue level.
• Both TNF receptors were observed to increase following disease, with TNFR-1 being the dominant receptor during the disease process, especially within chorioallantois (an important fetal membrane in the mare’s pregnancy) where minimal signaling took place in the endometrium (the inner lining of the uterus).

Conclusion

• The research concludes that TNF plays a pivotal role in the disease mechanisms of ascending placentitis.
• An increase in TNF during advanced stages of disease appears to trigger TNFR-1 within the chorioallantois, which results in various damaging outcomes such as programmed cell death (apoptosis) and destructive cell death (necroptosis), potentially signaling for fetal demise and the advent of abortion.