Oxidative stress and mitochondrial dysfunction of granulosa cells in polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is one of the leading causes of anovulatory infertility in women, affecting 5%-15% of women of reproductive age worldwide. The clinical manifestations of patients include ovulation disorders, amenorrhea, hirsutism, and obesity. Life-threatening diseases, such as endometrial cancer, type 2 diabetes, hyperlipidaemia, hypertension, and cardiovascular disease, can be distant complications of PCOS. PCOS has diverse etiologies and oxidative stress (OS) plays an important role. Mitochondria, as the core organelles of energy production, are the main source of reactive oxygen species (ROS). The process of follicular growth and development is extremely complex, and the granulosa cells (GCs) are inextricably linked to follicular development. The abnormal function of GCs may directly affect follicular development and alter many symptoms of PCOS. Significantly higher levels of OS markers and abnormal mitochondrial function in GCs have been found in patients with PCOS compared to healthy subjects, suggesting that increased OS is associated with PCOS progression. Therefore, the aim of this review was to summarize and discuss the findings suggesting that OS and mitochondrial dysfunction in GCs impair ovarian function and induce PCOS.

Corrigendum: Arachidonic acid in follicular fluid of PCOS induces oxidative stress in a human ovarian granulosa tumor cell line (KGN) and upregulates GDF15 expression as a response.

[This corrects the article DOI: 10.3389/fendo.2022.865748.].

Arachidonic Acid in Follicular Fluid of PCOS Induces Oxidative Stress in a Human Ovarian Granulosa Tumor Cell Line (KGN) and Upregulates GDF15 Expression as a Response.

Polycystic ovarian ovary syndrome (PCOS) is the main cause of ovulatory infertility and a common reproductive endocrine disease of women in reproductive age. In addition, nearly half of PCOS patients are associated with obesity, and their total free fatty acids tend to increase. Arachidonic acid (AA) is a polyunsaturated fatty acid. Oxidation products of AA reacting with various enzymes[cyclooxygenases (COX), lipoxygenases (LOX), cytochrome P450s (CYP)] can change cellular mitochondrial distribution and calcium ion concentration, and increase reactive oxygen species (ROS) production. In this study, we analyzed the follicular fluid fatty acids and found higher levels of C20:4n6 (AA) in PCOS patients than in normal control subjects. Also, to determine whether AA induces oxidative stress (OS) in the human ovarian granulosa tumor cell line (KGN) and affects its function, we treated KGN cells with or without reduced glutathione (GSH) and then stimulated them with AA. The results showed that AA significantly reduced the total antioxidant capacity (TAC) and activity of antioxidant enzymes and increased the malondialdehyde (MDA), ROS and superoxide anion(O2-)levels in KGN cells. In addition, AA was also found to impair the secretory and mitochondrial functions of KGN cells and induce their apoptosis. We further investigated the downstream genes affected by AA in KGN cells and its mechanism of action. We found that AA upregulated the expression of growth differentiation factor 15 (GDF15), which had a protective effect on inflammation and tissue damage. Therefore, we investigated whether AA-induced OS in KGN cells upregulates GDF15 expression as an OS response.Through silencing of GDF15 and supplementation with recombinant GDF15 (rGDF15), we found that GDF15, expressed as an OS response, protected KGN cells against AA-induced OS effects, such as impairment of secretory and mitochondrial functions and apoptosis. Therefore, this study suggested that AA might induce OS in KGN cells and upregulate the expression of GDF15 as a response to OS.

A Comprehensive Overview of circRNAs: Emerging Biomarkers and Potential Therapeutics in Gynecological Cancers.

Circular RNA (circRNA) is a highly conserved, stable and abundant non-coding RNA (ncRNA). Also, some circRNAs play an essential part in the progression of human cancers. CircRNA is different from traditional linear RNA. CircRNA has a closed circular structure, so it is resistant to exonuclease-mediated degradation and is more stable than linear RNA. Numerous studies have found that many circRNAs can act as a microRNA (miRNA) sponge, interact with RNA-binding proteins, regulate gene transcription, affect alternative splicing and be translated into proteins. Recently, some studies have also indicated that circRNA participates in the progression of gynecological cancers. In addition, circRNA can act as a promising biomarker for the diagnosis of gynecological tumors. Additionally, they can also play a key role in the prognosis of gynecological tumors. Furthermore, to our delight, circRNA may be a potential therapeutic target in gynecological cancers and widely used in clinical practice. This article reviews the functions and related molecular mechanisms of circRNAs in gynecological tumors, and discusses their potential as biomarkers for diagnostic and prognostic and therapeutic targets for gynecological cancers.

Stem Cell-Based Therapy for Asherman Syndrome: Promises and Challenges.

Asherman syndrome (AS) has an adverse effect on reproductive health and fertility by affecting endometrial regeneration. Stem cell-based therapies hold promise for future use in activating non-functional endometrium and reconstructing the endometrium in vivo. It has been postulated that various endometrial stem cells (EnSCs) are responsible for endometrial regeneration. Numerous studies have focused on bone marrow-derived stem cells (BMDSCs), which may provide new ideas for repairing endometrial lesions and reconstructing the endometrium. Other sources of stem cells, such as menstrual blood, umbilical cord, and amniotic membrane, have also attracted much attention as candidates for transplantation in AS. This review discusses the features and specific biomarkers among four types of resident endometrial stem cells, applications of four different sources of exogenous stem cells in AS, and development of stem cell therapy using biomaterials and exosomes.