Defensin-B gene’s possible role in equine endometriosis explored

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Different expression of the Defensin-B gene may play a role in the development of endometriosis in mares, the findings of research suggest.

β-defensins (DEFB) comprise a cluster of genes that have been shown to express themselves in various parts of the equine female and male reproductive system.

Despite being a major cause of infertility in mares, the mechanisms behind equine endometriosis remain unclear and controversial, Martina Crociati and her colleagues wrote in the journal BMC Veterinary Research.

In the last few years, many investigations have focused on local immune response modulation.

Since it is generally accepted that endometrial fibrosis increases with age, the research team hypothesized that older mares could show altered local immune modulation.

This, they suggested, could initiate a pro-inflammatory cascade of events that leads to tissue remodelling and ultimately endometriosis.

In their study, the researchers set out to evaluate and describe the local expression of genes involved in acute inflammatory response and fibrosis – COL1A1, COL3A1, TNFA, MMP9, IL6, TGFB1 and TGFBR1 – together with others associated with immune modulation (DEFB4B, IDO1 and FOXP3) in uterine specimens taken from mares of different age.

Gene expression is the process in which information from a gene is used in the manufacture of a functional gene product.

The study team used 25 Standardbred mares ranging in age from 7 to 19 years. Fifteen were aged under 10 and ten were older.

Specimens from the right horn-body junction of each horse’s uterus were collected and processed for microscopic evaluation and molecular-based testing.

Gene expression of DEFB4B, MMP9 and TNFA was found to be higher in younger mares, suggesting a balance in immune modulation and tissue remodeling.

Interleukin-6 and COL3A1 gene expressions were greater in older animals, probably indicating inflammatory pathways activation and fibrosis increase.

Although no differences in fibrosis and inflammation distribution could be found in microscopic examination of tissue samples between the older and younger mares, the results suggested a possible involvement of DEF4BB in regulating the local immune response in the uterus of younger mares.

Age, they said, may contribute to the dis-regulation of DEFB4B transcription (transcription is the first step in gene expression) and, indirectly, influence the balance in the extracellular matrix homeostasis.

Transcription of IDO1 and FOXP3 genes, instead, does not seem to be age-related, or to be involved in local immune-response and tissue remodeling functions.

The researchers said further investigations are needed to clarify the interactions between the expression of DEFB4B, IL6, TNFA, COL3A1 and MMP9 and other local signals of immune-modulation and tissue remodeling in the uterine tissue of mares.

Crociati, M., Capomaccio, S., Mandara, M.T. et al. Different expression of Defensin-B gene in the endometrium of mares of different age during the breeding season. BMC Vet Res 15, 465 (2019) doi:10.1186/s12917-019-2215-z

The study, published under a Creative Commons License, can be read here

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