Researchers have cast fresh light on molecular mechanisms underlying equine endometrosis, a common cause of poor fertility in mares.
Endometrosis is an important disease of the endometrium (the uterine lining) associated with epithelial and stromal cell changes, endometrium gland degeneration, and fibrosis (thickening or scarring of tissue).
Multiple degenerative changes are found in the uterine linings of mares with the condition. However, how the disease develops and progresses is not well known.
Tomasz Jasiński and his fellow researchers, writing in the International Journal of Molecular Sciences, said it is thought that nuclear factor-κB (NF-κB) – a cell metabolism regulator – and its activation pathways play a part in the development of the condition.
In their study, 100 samples of the uterine linings of mares at different stages of their estrus cycle were collected for evaluation.
This study sought to investigate the transcription of genes of estrogen (ESR1, ESR2) and progesterone receptors (PGR) in the samples to find relationships between the endocrine environment, the NF-κB-pathway, and fibrosis.
Transcription is the process in which information coded in a strand of DNA is copied into a new molecule of messenger RNA.
The study team used microscopic examination as well as molecular-based testing methods.
The study team found that the transcription of the profibrotic pathway genes of the NF-κB in fibrotic endometria differed between the phases of the estrous cycle, as well as with fibrosis progression.
The transcription of ESR1, ESR2, and PGR decreased with the severity of degeneration in the uterine lining, with differences noted in different stages of the estrus cycle. The results, they said, showed a clear relationship between the destructiveness of fibrosis and declining levels of gene transcription in both phases of the estrous cycle.
“In comparison to the unaffected endometrium, the transcription of ESR1, ESR2, and PGR decreased with the severity of endometrial fibrosis as well as in inactive and active types of destructive endometrosis.”
It is clear, they said, that the transcription of endometrial steroid receptors is subject to dysregulation, clearly linked to the severity of equine endometrosis, especially in the two destructive forms of the disease.
Moreover, the estrogen receptor-dependent rather than progesterone receptor-dependent deregulation seems to play a greater role in the progression of endometrosis.
“The role of the so far not assessed ESR2 should be investigated,” they said. Also, the specific relationship of corresponding proteins in the uterine lining requires further research.
Further work is required to establish the clinical applicability of research findings on possible treatments for endometrosis in horses, they said.
The study team comprised Jasiński, Łukasz Zdrojkowski, Ewa Kautz and Małgorzata Domino, all with the Warsaw University of Life Sciences in Poland; Graça Ferreira-Dias, with the University of Lisbon in Portugal; and Edyta Juszczuk-Kubiak, with the Wacław Dąbrowski Institute of Agricultural and Food Biotechnology – State Research Institute.
Jasiński, T.; Zdrojkowski, Ł.; Ferreira-Dias, G.; Kautz, E.; Juszczuk-Kubiak, E.; Domino, M. Molecular Mechanism of Equine Endometrosis: The NF-κB-Dependent Pathway Underlies the Ovarian Steroid Receptors’ Dysfunction. Int. J. Mol. Sci. 2022, 23, 7360. https://doi.org/10.3390/ijms23137360