Can Inflammatory Markers in Low-Volume Uterine Lavage Fluid be used to Diagnose Mares with Endometrial Fibrosis and with Acute Inflammation?
Fellow: Jennine Lection
Mentor: Mariana Diel de Amorim
Co-Mentor: Soon Hon Cheong, Bettina Wagner
DESCRIPTION (provided by applicant):
Uterine pathology is a major cause of infertility in horses. Inflammation and fibrosis are the most important and common pathologies seen in uterine biopsy of mares. Based on the severity of these changes, the mares can be scored according to the well-established Kenny-Doig system to predict the likelihood of carrying a foal to term. A score of I or IIA without active inflammation indicates a >50% likelihood to carry a foal to term while a score of IIB or III especially with the presence of inflammation has <50% likelihood to carry a foal to term. One limitation of this system is the long turn-around time to get the histological grading, but other diagnostic methods such as cytology lacks sensitivity. Therefore, our broad objective is to identify inflammatory markers for fibrosis and acute inflammation in low-volume uterine lavage (LVL) samples of mares with worse endometrial gradings (IIB and III) and with endometritis. Thirty estrus mares will be used in the study. The mares will have a LVL and endometrial biopsy performed, and they will be divided to three groups: 1) CONTROL group will have ten healthy mares (endometrial biopsy scores I and IIA without the presence of acute inflammation), 2) ACUTE group will have ten mares with cytologic evidence of acute endometritis (>1% PMNs) and 3) CHRONIC group will have ten mares with histologic evidence of chronic inflammation (Biopsy score IIB/III). Aim 1 will be to test the hypothesis that markers of inflammation and fibrosis: connective tissue growth factor (CTGF), Annexin A1 (ANXA1), IFN-γ, IL-1β,IL-10,IL-17, sCD14, TNF-α, CCL2, CCL3,CCL5, and CCL11 in the LVL will be higher in the ACUTE and CHRONIC groups compared with CONTROL and aim 2 will look for differences between the ACUTE and CHRONIC groups. We anticipate that ACUTE and CHRONIC mares will have increased levels of CTGF, ANXA1, and chemokines in the and that there will be differences in which biomarkers are increased in the LVL between the ACUTE and CHRONIC groups. This research will provide more insight in the molecular regulation of endometrial inflammatory response, which may impact the current diagnostic capability of equine practitioners.