Polycystic ovarian syndrome alters the expression of molecules involved in the uterine functional differentiation of peripubertal rats.

ALTAMIRANO, GABRIELA A.; BOSQUIAZZO, VERÓNICA L.; ACOSTA, MARIA V.; KASS, LAURA; BRACHO, GISELA S.; LUQUE, ENRIQUE H.

Congreso; Reunión Anual de Sociedades de Biociencias.; 2020

Sociedad Argentina de Investigación Clínica

The uterus functional differentiation is a process that involves changes in cell proliferation and differentiation at all stages of life. Polycystic ovarian syndrome (PCOS) is associated with higher risk of infertility and endometrial hyperplasia. The aim of this study was to evaluate whether PCOS alters the expression of molecules involved in functional differentiation of the rat uterus. To induce PCOS, Wistar rats were injected subcutaneously with dehydroepiandrosterone (6mg/100g body weight, PCOS group) from postnatal day 21 (PND21) to PND40, control group receive sesame oil. At PND41, the uterine horns were collected. Molecules involved in cell growth and proliferation [ie: Insulin-like growth factor 1 (IGF-1), IGF-1 receptor (IGF-1R), Homeobox gene A10 (Hoxa10), phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase (PTEN)] and involved in uterine development and differentiation [ie: Wingless-related MMTV integration site member 5a and 7a (Wnt5a and Wn7a) and β-catenin] were evaluated by RT-PCR and/or immunohistochemistry. In PCOS rats, IGF-1 mRNA was increased whereas IGF-1R mRNA was similar to Control rats. Hoxa10 mRNA expression was similar between experimental groups whereas the expression of the tumor suppressor gene, PTEN, was decreased both in subepithelial stroma and in myometrium of PCOS rats. In these rats, Wnt7a mRNA was not modified but a decrease of Wnt5a (mRNA and protein) and an increase of β-catenin (mRNA and protein) was observed. Wnt5a was expressed in all uterine compartments whereas β-catenin was markedly expressed in the cell membrane of epithelial cells. The results suggest that increased IGF-1 and decreased PTEN could be responsible for dysregulation of uterine cell proliferation in PCOS rats. Furthermore, the decrease in Wnt5a and the increase in β-catenin in the cell membrane suggest a down-regulation of mechanism regulated by canonical Wnt signaling. These changes may help explain the uterine abnormalities observed in women with PCOS.