Interleukins Affect Equine Endometrial Cell Function: Modulatory Action of Ovarian Steroids

Szóstek, A.Z.; Galvão, António; Hojo, Takuo; Okuda, Kiyoshi; Skarzynski, Dariusz J.

doi:10.1155/2014/208103

Cited by 14 publications

(6 citation statements)

References 49 publications

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“…Such differences may be hormone-dependent and mediated by tissue specific catabolic or anabolic enzymes involved in PG synthesis. In vitro studies have shown that ovarian steroids not only trigger PG production, but also modulate mare endometrial cell response to interleukins [ 56 ]. In a previous work on steroid regulation of PG synthesis, after in vitro exposure of mare endometrium to estrogen, a dose-dependent stimulation of PGF 2α production was observed, while exposure of tissues to progesterone failed to alter PGF 2α secretion [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Enzymes Present in Neutrophil Extracellular Traps May Stimulate the Fibrogenic PGF2α Pathway in the Mare Endometrium

Rebordão

Amaral

Fernandes

et al. 2021

Animals

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Endometrosis, a fibrotic disease of mare endometrium, impairs uterine function. Prostaglandins (PG), despite modulating reproductive physiological functions, may also cause local pathological collagen deposition (fibrogenesis). We have previously shown that neutrophil extracellular traps (NETs) may also favor mare endometrosis. The aim of this study was to investigate the effect of enzymes present in NETs on PGF2α-pathway activation. Kenney and Doig’s type I/IIA and IIB/III mare endometria, from follicular phase (FLP) and mid-luteal (MLP) phase, were cultured in vitro in the presence of NETs enzymes (elastase, cathepsin-G or myeloperoxidase). Production of PGF2α (EIA) and transcription (qPCR) of its synthases (PTGS2, AKR1C3) and receptor (PTGFR) genes were evaluated. PGF2α and PTGFR were influenced by endometrial category and estrous cycle phase. In FLP endometrium, NETs enzymes induced both high PGF2α production and/or PTGFR transcription. In MLP type I/IIA tissues, down-regulation of PTGFR transcripts occurred. However, in MLP type IIB/III endometrium, high levels of PTGFR transcripts were induced by NETs enzymes. As PGF2α-pathway activation facilitates fibrogenesis in other tissues, PGF2α may be involved in endometrosis pathogenesis. In the mare, the endocrine microenvironment of healthy and pathological endometrium might modulate the PGF2α pathway, as well as fibrosis outcome on endometrium challenged by NETs enzymes.

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Section: Discussionmentioning

confidence: 99%

Enzymes Present in Neutrophil Extracellular Traps May Stimulate the Fibrogenic PGF2α Pathway in the Mare Endometrium

Rebordão

Amaral

Fernandes

et al. 2021

Animals

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“…TNF is released by activated monocytes and macrophages and signals and regulates the synthesis of other cytokines, immune cells and inflammatory mediators (Papanicolaou, Chrysomali, Stylogianni, Donta, & Vlachodimitropoulos, ). In the equine uterus, TNF is produced by the stromal and epithelial cells of the endometrium, and expression of TNF is regulated by ovarian steroids (Szostek, Galvao, Hojo, Okuda, & Skarzynski, ). Numerous studies have demonstrated that TNF is significantly increased during endometritis in multiple species.…”

Section: Discussionmentioning

confidence: 99%

The effect of select seminal plasma proteins on endometrial mRNA cytokine expression in mares susceptible to persistent mating‐induced endometritis

Fedorka

Scoggin

Woodward

et al. 2016

Reprod Domestic Animals

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In the horse, breeding induces a transient endometrial inflammation. A subset of mares are unable to resolve this inflammation, and they are considered susceptible to persistent mating-induced endometritis PMIE Select seminal plasma proteins cysteine-rich secretory protein-3 (CRISP-3) and lactoferrin have been shown to affect the innate immune response to sperm in vitro. The objective of this study was to determine whether the addition of CRISP-3 and lactoferrin at the time of insemination had an effect on the mRNA expression of endometrial cytokines in susceptible mares after breeding. Six mares classified as susceptible to PMIE were inseminated during four consecutive oestrous cycles with treatments in randomized order of: 1 mg/ml CRISP-3, 150 μg/ml lactoferrin, seminal plasma (positive control) or lactated Ringer's solution (LRS; negative control) to a total volume of 10 ml combined with 1 × 10 spermatozoa pooled from two stallions. Six hours after treatment, an endometrial biopsy was obtained for qPCR analysis of selected genes associated with inflammation (pro-inflammatory cytokines interleukin (IL)-1β, IL-8, tumour necrosis factor (TNF)-α, interferon (INF)-γ, anti-inflammatory cytokines IL-1RN and IL-10, and inflammatory-modulating cytokine IL-6). Seminal plasma treatment increased the mRNA expression of IL-1β (p = .019) and IL-8 (p = .0068), while suppressing the mRNA expression of TNF (p = .0013). Lactoferrin also suppressed the mRNA expression of TNF (p = .0013). In conclusion, exogenous lactoferrin may be considered as one modulator of the complex series of events resulting in the poorly regulated pro-inflammatory response seen in susceptible mares.

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“…Interleukin-1 alpha, interleukin-1 beta, and interleukin-6 stimulate the production of PGF2α and PGE2 by epithelial and stromal cells in vitro, with estrogen and progesterone modulating the response (Szostek et al 2014 ). Tumor necrosis factor alpha stimulates prostaglandin production by mixed epithelial and stromal cells in vitro obtained from mare during the follicular phase but not when cells were obtained from mares during the mid-luteal phase (Galvao et al 2013 ).…”

Section: Regulation Of the Pathway For Prostaglandin Synthesismentioning

confidence: 95%

Pregnancy Recognition and Implantation of the Conceptus in the Mare

Klein

2015

Regulation of Implantation and Establishment of Pregnancy in Mammals

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Few, if any, biological processes are as diverse among domestic species as establishment of early pregnancy, in particular maternal recognition of pregnancy. Following fertilization and initial development in the mare oviduct, selective transport of the embryo through the uterotubal junction driven by embryo-derived PGE2 occurs. Upon arrival in the uterus, an acellular glycoprotein capsule is formed that covers the embryo, blastocyst, and conceptus (embryo and associated extraembryonic membranes) between the second and third weeks of pregnancy. Between Days 9 and 15/16 of pregnancy, the conceptus undergoes an extended phase of mobility. Conceptus mobility is driven by conceptus-derived PGF2α and PGE2 that stimulate uterine contractions which in turn propel migration of the conceptus within the uterine lumen. Cessation of conceptus mobility is referred to as fixation and appears to be attributable to increasing size of the conceptus, preferential thickening of the endometrium near the mesometrial attachment referred to as encroachment, and a reduction in sialic acid content of the capsule. During maternal recognition of pregnancy, endometrial PGF2α release is attenuated, a consequence of reduced expression of key enzymes involved in prostaglandin production. Oxytocin responsiveness is altered during early pregnancy, and reduced expression of the oxytocin receptor appears to be regulated at the posttranscriptional level rather than the transcriptional level. Prostaglandin release is attenuated temporarily only during early pregnancy; during the third week of pregnancy, the endometrium resumes the ability to secrete PGF2α. The equine conceptus initiates steroidogenesis as early as Day 6 and synthesizes estrogens, androgens, and progesterone. Estrogens are metabolized locally, presumably regulating their bioavailability and actions. Results of experiments attempting to prove that conceptus-derived estrogens are responsible for extension of corpus luteum function have been inconclusive. By the fourth week of pregnancy, the chorionic girdle becomes visible on the trophoblast. Subsequent invasion of chorionic girdle cells leads to formation of endometrial cups which secrete equine chorionic gonadotropin. Equine chorionic gonadotropin has luteinizing hormone functions in the mare, causing luteinization of follicles resulting in the formation of secondary corpora lutea essential to production of progesterone and maintenance of pregnancy.

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Interleukins Affect Equine Endometrial Cell Function: Modulatory Action of Ovarian Steroids

Cited by 14 publications

References 49 publications

Enzymes Present in Neutrophil Extracellular Traps May Stimulate the Fibrogenic PGF2α Pathway in the Mare Endometrium

Enzymes Present in Neutrophil Extracellular Traps May Stimulate the Fibrogenic PGF2α Pathway in the Mare Endometrium

The effect of select seminal plasma proteins on endometrial mRNA cytokine expression in mares susceptible to persistent mating‐induced endometritis

Pregnancy Recognition and Implantation of the Conceptus in the Mare

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