Reactive oxygen species‐induced SIAH1 promotes granulosa cells' senescence in premature ovarian failure

Abstract

Premature ovarian failure (POF) is a common disease in women, characterized as abnormal declines in ovarian follicle numbers and oocyte quality. Patients have early depletion of primordial follicle pool associated with amenorrhea before the age of 40, which could be diagnosed by elevated serum FSH levels (>40 IU/L). 1,2 Causes of this disease could be mitochondrial dysfunction, auto-immune, chemotherapeutic treatments and cell senescence. 3 During ageing and senescence, accumulation of endogenous reactive oxygen species (ROS) and weakened antioxidant defences promoted oxidative damage in cell structures, rendering membranal lipid peroxidation, enzyme inactivation, protein oxidation and DNA damage. 4,5 As stated in the widely acknowledged 'free radical theory', oxidative damage continuously occurs during ageing and ROS is the driving force of ageing and cell senescence, whereas ageing is also a result of oxidative damage. 6,7 In addition, crosstalk between oocytes and GCs regulates oocytes competency and female fertility, deciding

Preventive Electroacupuncture Alleviates Oxidative Stress and Inflammation via Keap1/Nrf2/HO-1 Pathway in Rats with Cyclophosphamide-Induced Premature Ovarian Insufficiency

“…Excess germinal primordial follicles, inadequate development of follicles at all stages, and follicular pool depletion result in diminished ovarian reserve [ 3 ]. Previous studies have shown that its mechanism is mainly through oxidative stress damage, affecting hormone levels, and inducing germ cell apoptosis [ 5 ]. Based on the literature, we established a CTX-induced chemogenic POI rat model [ 21 ] and investigated the effect of preventative acupuncture on the Keap/Nrf2/HO-1 pathway in the pathogenic phase of POI.…”

“…During the therapeutic process, blood circulation abnormalities and related body stress injuries might cause a large amount of free radicals to be released. It promotes peroxidation and releases a substantial number of reactive oxygen species (ROS) which will damage the mitochondrial membrane and cell membrane of ovarian granulosa cells, induce an inflammatory cascade, release alarm signals (alarmins), and initiate a cellular response [ 5 ]. Granulosa cells in the ovary offer an important environment for the formation and development of egg cells [ 6 ].…”

Human Umbilical Cord Mesenchymal Stem Cells Improve Premature Ovarian Failure through Cell Apoptosis of miR-100-5p/NOX4/NLRP3

“…Premature ovarian failure refers to a series of symptoms of perimenopausal hot flashes, night sweats, decreased libido, vaginal dryness, insomnia, reduced menstruation, sparse hair, even amenorrhea, and even infertility before the age of 40 due to the decline of ovarian function [ 1 , 2 ]. At the same time, it is accompanied by the decrease of estrogen, the increase of follicle stimulating hormone, and the increase or unchanged of luteinizing hormone [ 3 ].…”

Cellular senescence in the pathogenesis of ovarian dysfunction

“…This was indicated by high SA-β-gal activity and ROS accumulation, along with the expression of the machinery for telomere shortening, which is upregulated by p53. 33 The relationship of cellular senescence with POI induced by gonadotoxic agents has been more thoroughly investigated than that with the idiopathic form. Various agents used in chemotherapy, including methotrexate, cisplatin, doxorubicin, and cyclophosphamide, have been reported to induce cellular senescence in the ovary.…”

“…Another study showed that GCs from patients with idiopathic POI have a senescent phenotype, unlike those from age‐matched controls. This was indicated by high SA‐β‐gal activity and ROS accumulation, along with the expression of the machinery for telomere shortening, which is upregulated by p53 33 …”