Implications of the RhoA/Rho associated kinase pathway and leptin in primary uterine inertia in the dog
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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 Margaret; Kowalewski, Mariusz Pawel; Gram, Aykut; Keller, Stefanie; Goericke-Pesch, Sandra; Balogh, Orsolya.
In: The Journal of reproduction and development, Vol. 67, No. 3, 2021, p. 207-215.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Implications of the RhoA/Rho associated kinase pathway and leptin in primary uterine inertia in the dog
AU - Frehner, Bianca Lourdes
AU - Reichler, Iris Margaret
AU - Kowalewski, Mariusz Pawel
AU - Gram, Aykut
AU - Keller, Stefanie
AU - Goericke-Pesch, Sandra
AU - Balogh, Orsolya
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Canine
KW - Contractility
KW - Dystocia
KW - Parturition
KW - Uterus
U2 - 10.1262/jrd.2020-141
DO - 10.1262/jrd.2020-141
M3 - Journal article
C2 - 33746146
AN - SCOPUS:85108741828
VL - 67
SP - 207
EP - 215
JO - Journal of Reproduction and Development
JF - Journal of Reproduction and Development
SN - 0916-8818
IS - 3
ER -
ID: 273641338