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Simple Summary  Endometrosis is a serious problem mainly affecting older mares’ fertility. Despite the importance of this disease, its etiology and pathogenesis are not fully known. Thus, no effective treatment exists to cease or restore degenerative processes and fibrogenesis in the mares’ endometria. The nuclear factor kappaB (NF-κB) is an important factor regulating cell metabolism. Nevertheless, it is also known to promote inflammation and fibrosis in various tissues and species, as well as in the mares’ endometria. The main goal was to bring new knowledge regarding endometrosis pathogenesis, which could allow for therapy development. Endometrial samples, collected postmortem from cyclic mares in estrus or diestrus, were classified histologically and used for gene expression assessment. Gene transcription of NF-κB subunits (subunit RelA— RelA ; subunit 1— NF-κB1 ; subunit 2— NF-κB2 ), pro-inflammatory molecules (monocyte chemoattractant protein-1— MCP-1 ; interleukin-6— IL-6 ), and hyaluronan synthases (hyaluronan synthase 1— HAS 1 ; hyaluronan synthase 2— HAS 2 ; hyaluronan synthase 3— HAS 3 ) were compared among endometrosis types (active, non-active, destructive, non-destructive), according to the classification of Hoffmann and co-authors. These results suggest that activation of the NF-κB canonical pathway is involved especially in destructive endometrosis, the type when endometrial glands are damaged. These data give substantial information for further evaluations and treatment development.    Abstract  Endometrosis is an important mares’ disease which considerably decreases their fertility. As classic endometrial classification methods might be insufficient for tissue pathological evaluation, further categorization into active/inactive and destructive/non-destructive types was developed by Hoffmann and others. This study aimed to compare NF-κB pathway genes transcription among histopathological types of endometrosis, following Hoffmann and co-authors’ classification. Endometrial samples, collected postmortem from cyclic mares ( n  = 100) in estrus or diestrus, were classified histologically and used for gene transcription assessment. Gene transcription of NF-κB subunits ( RelA ,  NF-κB1 ,  NF-κB2 ), pro-inflammatory molecules ( MCP-1 ,  IL-6 ), and hyaluronan synthases ( HAS 1 ,  HAS 2 ,  HAS 3 ) was compared among endometrosis types (active, non-active, destructive, non-destructive). Most individual mRNA samples showed high expression of  RelA ,  NF-κB1 , and  MCP-1  gene transcripts and the destructive type of endometrosis, simultaneously. The expression of  RelA  and  NF-κB1  genes was higher in active destructive group than in the other groups only in the follicular phase, as well as being higher in the inactive destructive group than in the others, only in the mid-luteal phase. The increase in gene transcription of the NF-κB canonical activation pathway in destructive endometrosis may suggest the highest changes in extracellular matrix deposition. Moreover, the estrous cycle phase might influence fibrosis pathogenesis.

Equine Endometrosis Pathological Features: Are They Dependent on NF-κB Signaling Pathway?