Uterine responses and equine chorionic gonadotropin concentrations after two intrauterine infusions with kerosene post early fetal loss in mares

Podico, Giorgia; Canisso, Igor F.; Roady, Patrick J.; Austin, Scott M.; Carossino, Mariano; Balasuriya, Udeni B. R.; Ellerbrock, Robyn E.; Lima, F.S.; Ferreira‐Dias, Graça; Douglas, Robert H.

doi:10.1016/j.theriogenology.2019.11.014

Cited by 11 publications

(18 citation statements)

References 24 publications

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“…Despite decades of research on the treatment of endometrosis, no efficient therapy has been found. Even though claims have been made on the anecdotal use of intrauterine infusion of kerosene to treat endometrosis [60], no effect on the endometrium histopathology grade was noted [61]. In humans, for the treatment of pulmonary fibrotic conditions, SIV has been administered intravenously [24,47].…”

Section: Discussionmentioning

confidence: 99%

The In Vitro Inhibitory Effect of Sivelestat on Elastase Induced Collagen and Metallopeptidase Expression in Equine Endometrium

Amaral

Fernandes

Rebordão

et al. 2020

Animals

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Neutrophil extracellular traps (NETs) fight endometritis, and elastase (ELA), a protease found in NETs, might induce collagen type I (COL1) accumulation in equine endometrium. Metallopeptidases (MMPs) are involved in extracellular matrix balance. The aim was to evaluate the effects of ELA and sivelestat (selective elastase inhibitor) on MMP-2 and MMP-9 expression and gelatinolytic activity, as well as the potential inhibitory effect of sivelestat on ELA-induced COL1 in equine endometrium. Endometrial explants from follicular (FP) and mid-luteal (MLP) phases were treated for 24 or 48 h with ELA, sivelestat, and their combination. Transcripts of COL1A2, MMP2, and MMP9 were evaluated by qPCR; COL1 protein relative abundance by Western blot, and MMP-2 and MMP-9 gelatinolytic activity by zymography. In response to ELA treatment, there was an increase in MMP2 mRNA transcription (24 h) in active MMP-2 (48 h), both in FP, and in MMP9 transcripts in FP (48 h) and MLP (24 h) (p < 0.05). Sivelestat inhibited ELA-induced COL1A2 transcripts in FP (24 h) and MLP (24 h, 48 h) (p < 0.05). The sivelestat inhibitory effect was detected in MMP9 transcripts in FP at 48 h (p < 0.05), but proteases activity was unchanged. Thus, MMP-2 and MMP-9 might be implicated in endometrium fibrotic response to ELA. In mare endometrium, sivelestat may decrease ELA-induced COL1 deposition and hinder endometrosis development.

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Section: Discussionmentioning

confidence: 99%

The In Vitro Inhibitory Effect of Sivelestat on Elastase Induced Collagen and Metallopeptidase Expression in Equine Endometrium

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Fernandes

Rebordão

et al. 2020

Animals

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“…Thus, a picrosirius red solution was placed onto deparaffinized endometrium sections and incubated for 1 h. Afterward, slides were rinsed with acetic acid solution and absolute alcohol. The slides were observed with an upright widefield microscope (Olympus BX51, Olympus Corporation, Tokyo, Japan) at 200× magnification (20×/0.75NA objective) under polarized light, and ten random images from each stained endometrium section were acquired with a camera (TIS 2MP RGB), with a pixel size of 0.441 μm/pixel ( 12 ). Collagen type one fibers appeared in red, while COL3 fibers stained green.…”

Section: Methodsmentioning

confidence: 99%

“…Nevertheless, in the mare endometrium at the transcript level, age appeared not to influence COL1 or COL3 mRNA (10). In contrast, quantification of the areas in the endometrium occupied by COL1 and COL3, stained with histochemical picrosirius red staining and visualized by polarized light microscopy (11,12), showed an increase in COL1 in the tissues with severe endometriosis, in comparison to healthy endometria or with mild fibrotic changes, where COL3 was the most predominant type (10). A previous morphometric analysis of periglandular fibrosis in equine endometria using picrosirius red also referred a predominance of COL1 in severe endometriosis (13).…”

Section: Introductionmentioning

confidence: 99%

Collagen and Eosinophils in Jenny's Endometrium: Do They Differ With Endometrial Classification?

et al. 2020

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Collagen fibers and inflammatory cells are the basis for jenny endometrium Kenney and Doig's classification developed for the mare. The infiltration of a large number of eosinophils in the jenny endometrium is intriguing. Eosinophil and fibroblast produced IL33, which has been related to fibrosis development and chronicity. This work on the endometrium consisted of (i) quantification of collagen type I (COL1A2), type III (COL3A1), and IL33 transcripts; (ii) histological localization and quantification of COL1 and COL3 proteins; and (iii) eosinophil and neutrophil count and correlation with collagen area and IL33 transcripts. Localization of COL protein in the jenny endometrium was also compared to the mare endometrium. As fibrosis increased, eosinophil and neutrophil count decreased ( P < 0.05). A 5-fold increase in IL33 transcripts was noted from categories IIA to III. There was a tendency toward a positive correlation between eosinophil count and IL33 transcripts in category IIA endometrium ( P = 0.055). Neither transcripts of COL1A2 nor COL3A1 nor the areas of COL1 or COL3 differed with endometrial categories. Unlike for the mare, and regardless of the jenny endometrium classification, COL3 was always found to different extents in the stratum compactum, while COL1 was mainly present in deep stroma. As fibrosis progressed in the mare, an extensive increase in COL1 fibers was notorious under the surface epithelium. Correlations between neutrophil count and COL1 and COL3 areas were observed in the jenny endometrium, although no correlation was found for eosinophil count. Neutrophil count positive correlation with the COL1 area and negative correlation with the COL3 area in endometria with mild lesions suggest that neutrophils in the jenny endometrium may be involved in fibrogenesis. In addition, when eosinophilia subsides, the endometrium reacts with fibrosis establishment, which could be stimulated by the pro-fibrotic cytokine IL33, whose release might then be ascribed to fibroblasts. Further studies are needed to analyze the effect of the presence of COL3 next to the surface epithelium in the stratum compactum, or around the endometrial glands on jenny's endometrial function and fertility.

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“…During the last decades, the use of dimethyl sulfoxide [ 32 ], kerosene [ 33 ], or mesenchymal stem cells [ 34 , 35 ] were proposed to treat mare endometritis and/or endometrosis. Unfortunately, none of the proposed treatments revealed themselves as effective on endometrial fibrosis reduction, nor increased fertility rates.…”

Section: Introductionmentioning

confidence: 99%

Noscapine Acts as a Protease Inhibitor of In Vitro Elastase-Induced Collagen Deposition in Equine Endometrium

Amaral

Fernandes

Szóstek‐Mioduchowska

et al. 2021

IJMS

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Endometrosis is a reproductive pathology that is responsible for mare infertility. Our recent studies have focused on the involvement of neutrophil extracellular traps enzymes, such as elastase (ELA), in the development of equine endometrosis. Noscapine (NOSC) is an alkaloid derived from poppy opium with anticough, antistroke, anticancer, and antifibrotic properties. The present work investigates the putative inhibitory in vitro effect of NOSC on collagen type I alpha 2 chain (COL1A2) mRNA and COL1 protein relative abundance induced by ELA in endometrial explants of mares in the follicular or mid-luteal phases at 24 or 48 h of treatment. The COL1A2 mRNA was evaluated by qPCR and COL1 protein relative abundance by Western blot. In equine endometrial explants, ELA increased COL 1 expression, while NOSC inhibited it at both estrous cycle phases and treatment times. These findings contribute to the future development of new endometrosis treatment approaches. Noscapine could be a drug capable of preventing collagen synthesis in mare’s endometrium and facilitate the therapeutic approach.

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Uterine responses and equine chorionic gonadotropin concentrations after two intrauterine infusions with kerosene post early fetal loss in mares

Cited by 11 publications

References 24 publications

The In Vitro Inhibitory Effect of Sivelestat on Elastase Induced Collagen and Metallopeptidase Expression in Equine Endometrium

The In Vitro Inhibitory Effect of Sivelestat on Elastase Induced Collagen and Metallopeptidase Expression in Equine Endometrium

Collagen and Eosinophils in Jenny's Endometrium: Do They Differ With Endometrial Classification?

Noscapine Acts as a Protease Inhibitor of In Vitro Elastase-Induced Collagen Deposition in Equine Endometrium

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