Implications of the RhoA/Rho associated kinase pathway and leptin in primary uterine inertia in the dog

The underlying functional and molecular changes in canine primary uterine inertia (PUI) are still not clarified. Leptin (Lep) and obesity negatively affect uterine contractility in women, partly mediated by the RhoA/Rho associated kinase pathway, affecting myometrial calcium sensitization. We hypoth...

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Main Authors: Bianca Lourdes FREHNER, Iris Margaret REICHLER, Mariusz Pawel KOWALEWSKI, Aykut GRAM, Stefanie KELLER, Sandra GOERICKE-PESCH, Orsolya BALOGH
Format: Article
Language:English
Published: The Society for Reproduction and Development 2021-03-01
Series:The Journal of Reproduction and Development
Subjects:
Online Access:https://www.jstage.jst.go.jp/article/jrd/67/3/67_2020-141/_pdf/-char/en
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author Bianca Lourdes FREHNER
Iris Margaret REICHLER
Mariusz Pawel KOWALEWSKI
Aykut GRAM
Stefanie KELLER
Sandra GOERICKE-PESCH
Orsolya BALOGH
author_facet Bianca Lourdes FREHNER
Iris Margaret REICHLER
Mariusz Pawel KOWALEWSKI
Aykut GRAM
Stefanie KELLER
Sandra GOERICKE-PESCH
Orsolya BALOGH
author_sort Bianca Lourdes FREHNER
collection DOAJ
description The underlying functional and molecular changes in canine primary uterine inertia (PUI) are still not clarified. Leptin (Lep) and obesity negatively affect uterine contractility in women, partly mediated by the RhoA/Rho associated kinase pathway, affecting myometrial calcium sensitization. We hypothesized that increased uterine Lep/Lep receptor (LepR) or decreased RhoA/Rho associated kinase expression contributes to PUI in dogs, independent of obesity. Dogs presented for dystocia were grouped into PUI (n = 11) or obstructive dystocia (OD, still showing strong labor contractions; n = 7). Interplacental full-thickness uterine biopsies were collected during Cesarean section for relative gene expression (RGE) of RhoA, its effector kinases (ROCK1, ROCK2), Lep and LepR by qPCR. Protein and/or mRNA expression and localization was evaluated by immunohistochemistry and in situ hybridization. RGE was compared between groups by one-way ANOVA using body weight as covariate with statistical significance at P < 0.05. Uterine ROCK1 and ROCK2 gene expression was significantly higher in PUI than OD, while RhoA and Lep did not differ. LepR RGE was below the detection limit in five PUI and all OD dogs. Litter size had no influence. Lep, LepR, RhoA, ROCK1, ROCK2 protein and/or mRNA were localized in the myometrium and endometrium. Uterine protein expression appeared similar between groups. LepR mRNA signals appeared stronger in PUI than OD. In conclusion, lasting, strong labor contractions in OD likely resulted in downregulation of uterine ROCK1 and ROCK2, contrasting the higher expression in PUI dogs with insufficient contractions. The Lep-LepR system may affect uterine contractility in non-obese PUI dogs in a paracrine-autocrine manner.
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spelling doaj.art-63d7b43881dd41a8a4d267532ebd64852023-11-17T07:20:43ZengThe Society for Reproduction and DevelopmentThe Journal of Reproduction and Development0916-88181348-44002021-03-0167320721510.1262/jrd.2020-141jrdImplications of the RhoA/Rho associated kinase pathway and leptin in primary uterine inertia in the dogBianca Lourdes FREHNER0Iris Margaret REICHLER1Mariusz Pawel KOWALEWSKI2Aykut GRAM3Stefanie KELLER4Sandra GOERICKE-PESCH5Orsolya BALOGH6Clinic of Reproductive Medicine, Vetsuisse Faculty, University of Zurich, Zurich, SwitzerlandClinic of Reproductive Medicine, Vetsuisse Faculty, University of Zurich, Zurich, SwitzerlandInstitute of Veterinary Anatomy, Vetsuisse Faculty, University of Zurich, Zurich, SwitzerlandInstitute of Veterinary Anatomy, Vetsuisse Faculty, University of Zurich, Zurich, SwitzerlandClinic of Reproductive Medicine, Vetsuisse Faculty, University of Zurich, Zurich, SwitzerlandSection for Veterinary Reproduction and Obstetrics, Department of Veterinary Clinical Sciences, University of Copenhagen, Frederiksberg, DenmarkClinic of Reproductive Medicine, Vetsuisse Faculty, University of Zurich, Zurich, SwitzerlandThe underlying functional and molecular changes in canine primary uterine inertia (PUI) are still not clarified. Leptin (Lep) and obesity negatively affect uterine contractility in women, partly mediated by the RhoA/Rho associated kinase pathway, affecting myometrial calcium sensitization. We hypothesized that increased uterine Lep/Lep receptor (LepR) or decreased RhoA/Rho associated kinase expression contributes to PUI in dogs, independent of obesity. Dogs presented for dystocia were grouped into PUI (n = 11) or obstructive dystocia (OD, still showing strong labor contractions; n = 7). Interplacental full-thickness uterine biopsies were collected during Cesarean section for relative gene expression (RGE) of RhoA, its effector kinases (ROCK1, ROCK2), Lep and LepR by qPCR. Protein and/or mRNA expression and localization was evaluated by immunohistochemistry and in situ hybridization. RGE was compared between groups by one-way ANOVA using body weight as covariate with statistical significance at P < 0.05. Uterine ROCK1 and ROCK2 gene expression was significantly higher in PUI than OD, while RhoA and Lep did not differ. LepR RGE was below the detection limit in five PUI and all OD dogs. Litter size had no influence. Lep, LepR, RhoA, ROCK1, ROCK2 protein and/or mRNA were localized in the myometrium and endometrium. Uterine protein expression appeared similar between groups. LepR mRNA signals appeared stronger in PUI than OD. In conclusion, lasting, strong labor contractions in OD likely resulted in downregulation of uterine ROCK1 and ROCK2, contrasting the higher expression in PUI dogs with insufficient contractions. The Lep-LepR system may affect uterine contractility in non-obese PUI dogs in a paracrine-autocrine manner.https://www.jstage.jst.go.jp/article/jrd/67/3/67_2020-141/_pdf/-char/encaninecontractilitydystociaparturitionuterus
spellingShingle Bianca Lourdes FREHNER
Iris Margaret REICHLER
Mariusz Pawel KOWALEWSKI
Aykut GRAM
Stefanie KELLER
Sandra GOERICKE-PESCH
Orsolya BALOGH
Implications of the RhoA/Rho associated kinase pathway and leptin in primary uterine inertia in the dog
The Journal of Reproduction and Development
canine
contractility
dystocia
parturition
uterus
title Implications of the RhoA/Rho associated kinase pathway and leptin in primary uterine inertia in the dog
title_full Implications of the RhoA/Rho associated kinase pathway and leptin in primary uterine inertia in the dog
title_fullStr Implications of the RhoA/Rho associated kinase pathway and leptin in primary uterine inertia in the dog
title_full_unstemmed Implications of the RhoA/Rho associated kinase pathway and leptin in primary uterine inertia in the dog
title_short Implications of the RhoA/Rho associated kinase pathway and leptin in primary uterine inertia in the dog
title_sort implications of the rhoa rho associated kinase pathway and leptin in primary uterine inertia in the dog
topic canine
contractility
dystocia
parturition
uterus
url https://www.jstage.jst.go.jp/article/jrd/67/3/67_2020-141/_pdf/-char/en
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