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

Frehner, Bianca Lourdes; Reichler, Iris M; Kowalewski, Mariusz P; Gram, Aykut; Keller, Stefanie; Goericke-Pesch, Sandra; Balogh, Orsolya (2021). Implications of the RhoA/Rho associated kinase pathway and leptin in primary uterine inertia in the dog. Journal of Reproduction and Development, 67(3):207-215.

Abstract

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.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Veterinärwissenschaftliches Institut > Institute of Veterinary Anatomy
05 Vetsuisse Faculty > Veterinary Clinic > Department of Farm Animals
Dewey Decimal Classification:570 Life sciences; biology
630 Agriculture
Scopus Subject Areas:Life Sciences > Animal Science and Zoology
Uncontrolled Keywords:Animal Science and Zoology
Language:English
Date:1 January 2021
Deposited On:17 Dec 2021 15:00
Last Modified:26 Oct 2024 01:39
Publisher:Japanese Society of Animal Reproduction
ISSN:0916-8818
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1262/jrd.2020-141
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