I. Hamner, J. Howard, R.A. Crook, G. Unger, S.J. Coleman, P.M. McCue, C.E. Fedorka
{"title":"Investigation into the association between endometriosis and pituitary pars intermedia dysfunction (PPID)","authors":"I. Hamner, J. Howard, R.A. Crook, G. Unger, S.J. Coleman, P.M. McCue, C.E. Fedorka","doi":"10.1016/j.jevs.2025.105504","DOIUrl":null,"url":null,"abstract":"<div><div>Pituitary pars intermedia dysfunction (PPID) is an endocrine disorder associated with elevated adrenocorticotropin hormone (ACTH). Animals suffering from this disease have been found to have elevated systemic inflammation. It is unknown if this inflammation is noted within the reproductive tract, or if this inflammation is associated with fibrosis. Fibrosis of the endometrium, deemed endometriosis, is often noted in aged mares and is associated with subfertility. Therefore, the objective of this study is to evaluate endometriosis of the PPID mare. We hypothesize that elevated ACTH and its associated chronic inflammation will coincide with an increase in endometrial fibrosis. To evaluate this, 11 mares were screened for PPID in late summer using a thyrotropin-releasing hormone (TRH) stimulation test. In brief, ACTH concentrations were measured before and 1 h after stimulation with 1.0 mg TRH. Of these, 7 mares were found to be PPID positive (n = 7; ACTH >110 pg/mL), and 4 were found to be PPID negative (n = 4; ACTH <30 pg/mL). When mares were in diestrus (presence of a corpus luteum; uterine tone; P4 >4 ng/mL), 2 endometrial biopsies were then collected. One biopsy was processed for qPCR analysis of select inflammatory cytokines and the other was paraffin embedded for histology. Statistics were performed on SAS 9.4, and data were assessed for normality and equal variances utilizing a Bartlett's and Shapiro–Wilk test. Next, the impact of PPID on expression of transcripts associated with fibrosis (MMP1, MMP2, MMP9, TIMP-2, and TNF) were evaluated using an unequal variances <em>t</em>-test. Correlation between ACTH and expression of fibrosis markers was assessed using a Pearson correlation. Significance was set at <em>P</em> < 0.05. PPID was not found to affect the expression of any transcript evaluated, and this included MMP2 (<em>P</em> = 0.56), MMP9 (<em>P</em> = 0.91), TIMP-2 (<em>P</em> = 0.19), and TNF (<em>P</em> = 0.35). There was also no significant correlation between levels of ACTH and expression of fibrotic markers, including MMP2 (<em>P</em> = 0.61; R<sup>2</sup> = 0.04), MMP9 (<em>P</em> = 0.66; R<sup>2</sup> = 0.03), TIMP-2 (<em>P</em> = 0.97; R<sup>2</sup> < 0.01), or TNF (<em>P</em> = 0.53; R<sup>2</sup> = 0.05). Additionally, there was no significant difference when assessing fibrosis based on histology, as fibrosis was noted in 4 of 7 PPID animals and 2 of 4 control animals (<em>P</em> = 0.82). In conclusion, PPID does not appear to have a correlation with endometriosis.</div></div>","PeriodicalId":15798,"journal":{"name":"Journal of Equine Veterinary Science","volume":"148 ","pages":"Article 105504"},"PeriodicalIF":1.3000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Equine Veterinary Science","FirstCategoryId":"97","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0737080625001625","RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"VETERINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Pituitary pars intermedia dysfunction (PPID) is an endocrine disorder associated with elevated adrenocorticotropin hormone (ACTH). Animals suffering from this disease have been found to have elevated systemic inflammation. It is unknown if this inflammation is noted within the reproductive tract, or if this inflammation is associated with fibrosis. Fibrosis of the endometrium, deemed endometriosis, is often noted in aged mares and is associated with subfertility. Therefore, the objective of this study is to evaluate endometriosis of the PPID mare. We hypothesize that elevated ACTH and its associated chronic inflammation will coincide with an increase in endometrial fibrosis. To evaluate this, 11 mares were screened for PPID in late summer using a thyrotropin-releasing hormone (TRH) stimulation test. In brief, ACTH concentrations were measured before and 1 h after stimulation with 1.0 mg TRH. Of these, 7 mares were found to be PPID positive (n = 7; ACTH >110 pg/mL), and 4 were found to be PPID negative (n = 4; ACTH <30 pg/mL). When mares were in diestrus (presence of a corpus luteum; uterine tone; P4 >4 ng/mL), 2 endometrial biopsies were then collected. One biopsy was processed for qPCR analysis of select inflammatory cytokines and the other was paraffin embedded for histology. Statistics were performed on SAS 9.4, and data were assessed for normality and equal variances utilizing a Bartlett's and Shapiro–Wilk test. Next, the impact of PPID on expression of transcripts associated with fibrosis (MMP1, MMP2, MMP9, TIMP-2, and TNF) were evaluated using an unequal variances t-test. Correlation between ACTH and expression of fibrosis markers was assessed using a Pearson correlation. Significance was set at P < 0.05. PPID was not found to affect the expression of any transcript evaluated, and this included MMP2 (P = 0.56), MMP9 (P = 0.91), TIMP-2 (P = 0.19), and TNF (P = 0.35). There was also no significant correlation between levels of ACTH and expression of fibrotic markers, including MMP2 (P = 0.61; R2 = 0.04), MMP9 (P = 0.66; R2 = 0.03), TIMP-2 (P = 0.97; R2 < 0.01), or TNF (P = 0.53; R2 = 0.05). Additionally, there was no significant difference when assessing fibrosis based on histology, as fibrosis was noted in 4 of 7 PPID animals and 2 of 4 control animals (P = 0.82). In conclusion, PPID does not appear to have a correlation with endometriosis.
期刊介绍:
Journal of Equine Veterinary Science (JEVS) is an international publication designed for the practicing equine veterinarian, equine researcher, and other equine health care specialist. Published monthly, each issue of JEVS includes original research, reviews, case reports, short communications, and clinical techniques from leaders in the equine veterinary field, covering such topics as laminitis, reproduction, infectious disease, parasitology, behavior, podology, internal medicine, surgery and nutrition.