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Prostaglandin-mediated effects in early canine corpus luteum: In vivo effects on vascular and immune factors


Tavares Pereira, Miguel; Gram, Aykut; Nowaczyk, Renata; Boos, Alois; Hoffmann, Bernd; Janowski, Tomasz; Kowalewski, Mariusz P (2019). Prostaglandin-mediated effects in early canine corpus luteum: In vivo effects on vascular and immune factors. Reproductive Biology, 19(1):100-111.

Abstract

Prostaglandins (PGs) are important regulators of the early corpus luteum (CL) in the dog. Whereas, initially, CL is gonadotropin independent, in the second half of its lifespan, hypophyseal support is required. The transition period is marked by decreased availability of PGs, in particular of PGE2. We previously reported that inhibition of COX2/PTGS2 in vivo suppressed luteal production of PGE2, lowered circulating progesterone and negatively affected luteal development. Therefore, bitches were treated with a COX2-specific blocker, firocoxib, for 5, 10, 20 and 30 days after ovulation, leading to suppression of the steroidogenic machinery. Control groups received a placebo for the same periods. Considering the wide range of possible modulatory roles of PGs shown in different organ systems, this follow-up project aimed to understand further possible PG-mediated effects in early canine CL. Thirty-four (34) factors related predominantly to vascularization and immune response were screened (mRNAs and proteins) on samples from the above described in vivo study. Most of the effects were observed during the transitional period (days 20 and 30). The inhibition of COX2 diminished the expression of angiopoietin family members ANGPT1, -2, Tie1 and -2 receptors. The expression of endothelin (ET)-1 was increased. Concerning the immune system, increased expression of the pro-inflammatory cytokines, IL1β, IL6 and IL12a, and elevated expression levels of CD4, was observed. Cumulatively, besides its involvement in regulating steroidogenesis, our results indicate a broader role of PGs in the canine CL, including modulation of angiogenesis, vascular stabilization and local immunomodulation. Possible cross-species translational effects are strongly implied.

Abstract

Prostaglandins (PGs) are important regulators of the early corpus luteum (CL) in the dog. Whereas, initially, CL is gonadotropin independent, in the second half of its lifespan, hypophyseal support is required. The transition period is marked by decreased availability of PGs, in particular of PGE2. We previously reported that inhibition of COX2/PTGS2 in vivo suppressed luteal production of PGE2, lowered circulating progesterone and negatively affected luteal development. Therefore, bitches were treated with a COX2-specific blocker, firocoxib, for 5, 10, 20 and 30 days after ovulation, leading to suppression of the steroidogenic machinery. Control groups received a placebo for the same periods. Considering the wide range of possible modulatory roles of PGs shown in different organ systems, this follow-up project aimed to understand further possible PG-mediated effects in early canine CL. Thirty-four (34) factors related predominantly to vascularization and immune response were screened (mRNAs and proteins) on samples from the above described in vivo study. Most of the effects were observed during the transitional period (days 20 and 30). The inhibition of COX2 diminished the expression of angiopoietin family members ANGPT1, -2, Tie1 and -2 receptors. The expression of endothelin (ET)-1 was increased. Concerning the immune system, increased expression of the pro-inflammatory cytokines, IL1β, IL6 and IL12a, and elevated expression levels of CD4, was observed. Cumulatively, besides its involvement in regulating steroidogenesis, our results indicate a broader role of PGs in the canine CL, including modulation of angiogenesis, vascular stabilization and local immunomodulation. Possible cross-species translational effects are strongly implied.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Veterinary Anatomy
05 Vetsuisse Faculty > Center for Clinical Studies
Dewey Decimal Classification:570 Life sciences; biology
Uncontrolled Keywords:Developmental Biology, Animal Science and Zoology, Endocrinology, Corpus luteum; Dog (Canis lupus familiaris); Immune system; Prostaglandins; Vascularization
Language:English
Date:1 March 2019
Deposited On:29 Jan 2020 16:18
Last Modified:06 Feb 2020 12:38
Publisher:Elsevier
ISSN:1642-431X
OA Status:Green
Publisher DOI:https://doi.org/10.1016/j.repbio.2019.02.001
PubMed ID:30929911
Project Information:
  • : FunderSNSF
  • : Grant ID31003A_160251
  • : Project TitleEndocrine and cellular mechanisms of decidualization in the early pregnant canine uterus: remodelling processes and role of PGE2.

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