Miyuki Harada

On the basis of this current understanding, three areas are proposed to be subjects for future research, with the ultimate goals of developing therapeutic and preventive strategies and providing appropriate lifelong management, including preconception care.

Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and growth arrest of antral follicles. Previously, we found that endoplasmic reticulum (ER) stress is activated in granulosa cells of antral follicles in PCOS, evidenced by activation of unfolded protein response (UPR) genes. Based on this observation, we hypothesized that ER stress is activated by androgens in granulosa cells of antral follicles, and that activated ER stress promotes apoptosis via induction of the UPR transcri

Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism, and we previously found that androgens activate endoplasmic reticulum (ER) stress in granulosa cells from patients with PCOS. In addition, recent studies demonstrated the accumulation of advanced glycation end products (AGEs) in granulosa cells from PCOS patients, which contribute to the pathology. Therefore, we hypothesized that androgens upregulate the receptor for AGEs (RAGE) expression in granulosa cells by activating ER s

Intra-ovarian local factors regulate the follicular microenvironment in coordination with gonadotrophins, thus playing a crucial role in ovarian physiology as well as pathological states such as polycystic ovary syndrome (PCOS). One recently recognized local factor is endoplasmic reticulum (ER) stress, which involves the accumulation of unfolded or misfolded proteins in the ER related to various physiological and pathological conditions that increase the demand for protein folding or attenuate t

Uterine movement is suggested to play roles in various events related to the uterus. In view of the current concept underscoring the biological implications of mechanical stretch, we speculated that the mechanical stretch exerted by uterine movement might stimulate the production of biochemical mediators in endometrial cells and contribute to inflammation-associating processes, such as menstruation and endometriosis. To address the possible effects of mechanical stretch in the endometrium, endom

The objective of the present study is to investigate whether unfolded protein response (UPR), activated by endoplasmic reticulum (ER) stress, in granulosa cells (GC) and cumulus cells (CC) is involved in the process of follicular growth and maturation. First, to examine the presence of UPR in growing follicles, the expression of spliced form of X-box-binding protein 1 (XBP1(S)) and heat shock 70 kDa protein 5 (HSPA5) mRNA, typical UPR genes, in mice ovaries were examined by in situ hybridization

Endometriosis exerts detrimental effects on ovarian physiology and compromises follicular health. Granulosa cells from patients with endometriosis are characterized by increased apoptosis, as well as high oxidative stress. Endoplasmic reticulum (ER) stress, a local factor closely associated with oxidative stress, has emerged as a critical regulator of ovarian function. We hypothesized that ER stress is activated by high oxidative stress in granulosa cells in ovaries with endometrioma and that th

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-age women, affecting up to 15% of women in this group, and the most common cause of anovulatory infertility. Although its etiology remains unclear, recent research has revealed the critical role of endoplasmic reticulum (ER) stress in the pathophysiology of PCOS. ER stress is defined as a condition in which unfolded or misfolded proteins accumulate in the ER because of an imbalance in the demand for protein