Endoplasmic Reticulum Stress in Myometrial Smooth Muscle Cells and Spontaneous Contraction Changes in the Uterus of Dehydroepiandrosterone-induced Polycystic Ovary Syndrome Rats.

ABSTRACT

Myometrial changes in polycystic ovary syndrome (PCOS) are poorly investigated. Thus, we aimed to investigate endoplasmic reticulum (ER) stress in myometrial smooth muscle cells and changes in spontaneous uterine contraction in PCOS. Twenty-one female Sprague-Dawley rats (21 days old) were divided into control (n = 7), vehicle (n = 7) and PCOS (n = 7) groups. While the control group was not injected subcutaneously, the vehicle group was injected subcutaneously with sesame oil (0.2 ml/day) for 20 consecutive days. The PCOS group was injected subcutaneously with dehydroepiandrosterone (6 mg/100 g/day dissolved in 0.2 ml sesame oil) for 20 consecutive days. Blood samples were collected for the measurement of follicle stimulating-hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol (E2) and glucose-regulated protein 78 (GRP78). The mRNA expression of GRP78 in the uterine tissue samples was analysed by quantitative real-time polymerase chain reaction. GRP78 protein expression was assessed by immunohistochemistry. Myometrial smooth muscle cells were examined by transmission electron microscopy. Uterine contractions were evaluated with isolated organ bath experiments. In the PCOS group, T and LH levels increased significantly, although FSH and E2 levels decreased, but this decrease was not statistically significant. Additionally, GRP78 levels increased significantly in the PCOS group. In the PCOS group, the mRNA level, immunostaining intensity of GRP78, and ER damage grade increased, but the uterine tissue calcium levels, and the frequency and amplitude of spontaneous uterine contractions decreased. The results indicated that increased ER stress in myometrial smooth muscle cells may play a causative role in the decreased spontaneous uterine contractions in PCOS.