scholarly journals Moxibustion against Cyclophosphamide-Induced Premature Ovarian Failure in Rats through Inhibiting NLRP3-/Caspase-1-/GSDMD-Dependent Pyroptosis

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Cai-rong Zhang ◽  
Wei-na Zhu ◽  
Wei Tao ◽  
Wan-qi Lin ◽  
Chang-cheng Cheng ◽  
...  

Premature ovarian failure (POF) is a clinical term used to describe a condition in which women present with amenorrhoea, hypergonadotropic hypogonadism, and infertility under 40 years old, which are mainly characterized by ovarian granulosa cell inflammation and death. Pyroptosis is a proinflammatory form of programmed cell death. However, the roles of pyroptosis in POF and moxibustion (Mox) on pyroptosis in POF have not been elucidated. The aim of the present study was to investigate the protective effect of moxibustion against cyclophosphamide- (CP-) induced POF and to determine the underlying mechanisms. The results indicated that Mox could decrease the follicle-stimulating hormone (FSH) and luteotropic hormone (LH) and increase estradiol (E2) in serum, which indicated that it could improve ovarian reserve capacity. Mox also ameliorated CP-induced ovarian injury accompanied by decreased levels of interleukin-1β (IL-1β), IL-18, and gasdermin D (GSDMD), which are key features of pyroptosis. Further investigation showed that Mox alleviated POF through NLRP3-mediated pyroptosis. On the one hand, Mox directly inhibited TXNIP/NLRP3/caspase-1 signaling-induced pyroptosis, and on the other hand, it indirectly decreased NLRP3, pro-IL-1β, and pro-IL-18 through inhibiting TLR4/MyD88/NF-κB signaling. Our results show that Mox might be a new therapeutic strategy for the treatment of POF.

Author(s):  
Gerard S. Conway ◽  
Jacqueline Doyle ◽  
Melanie C. Melanie

The average age of menopause, denoted by the last menstrual period, occurs at an average age of 50.7 years in the western world (1) and this age has been found to be constant across generations, although one group have reported a secular trend to advancing menopausal age (2). The age of menopause in an individual is determined by both genetic and environmental factors (1, 3). Menopause before the age of 40 is most commonly taken to be the definition of ‘premature ovarian failure’ and this coincides approximately with youngest one percent of the frequency distribution of the age of menopause (Fig. 8.1.5.1). For every decade before 40 the prevalence of POF is estimated to decrease by a factor of 10. Thus, in presence of normal karyotype, 1:1000 of women at 30 has POF, 1:10 000 at 20 and 1:100 000 of women will present with gonadal failure and primary amenorrhoea. In terms of the mode of presentation, premature ovarian failure (POF) is the aetiology of 20% of cases with primary amenorrhoea and 10% of those with secondary amenorrhoea. Premature ovarian failure (POF) refers to the cessation of ovarian function at an earlier than expected age due to ovarian pathology. Primary ovarian failure is used in two contexts—to describe very early onset ovarian failure presenting with primary amenorrhoea and also to differentiate ovarian pathology from secondary ovarian failure, which refers to lack of ovarian activity as a result of gonadotropin deficiency. Primary ovarian insufficiency is recently favoured as an all-encompassing term that accounts for the variable course and occasional remission (4). The term hypergonadotropic hypogonadism is also used to emphasize ovarian origin. Resistant ovary syndrome (ROS) is an obsolete term, used to describe the coexistence of hypergonadotropic hypogonadism with normal ovarian follicles on histology of the ovary. It was soon realized that women with ROS progressed to complete ovarian failure and that ovarian follicles on histology were commonly found in established ovarian failure, negating the usefulness of this diagnostic label. Very early onset ovarian failure with a known genetic cause is often labelled inaccurately as ‘gonadal dysgenesis’ as in most situations it is thought that early ovarian development is normal.


2021 ◽  
Author(s):  
Xiaodan Lv ◽  
Chunyi Guan ◽  
Ying Li ◽  
Xing Su ◽  
lu Zhang ◽  
...  

Abstract BackgroundAt present, there is no effective treatment for premature ovarian failure (POF), and stem cell therapy is considered the most promising treatment. Human umbilical cord blood mesenchymal stem cells (hUC-MSCs) have shown good regenerative ability in a variety of diseases including POI, but the method and dosage of hUC-MSCs to treat POI are not clear. This study aims to explore the treatment options of hUC-MSCs for POF by comparing single injection and multiple injections of hUC-MSCs on the ovarian function repair of POF caused by chemotherapy drugs.MethodsFemale mice were injected intraperitoneally with 30 mg/kg of busulfan and 120 mg/kg of cyclophosphamide to induce POF. In the single hUC-MSCs injection group, 7 days after the mice were injected with cyclophosphamide and busulfan, hUC-MSCs were transplanted into these mice. In the multiple injection group, hUC-MSCs were transplanted 7 days, 14 days and 21 days after the mice were injected with cyclophosphamide and busulfan. We evaluated ovarian morphology, fertility, follicle stimulating hormone and estradiol concentration, and follicle count, evaluated POF model and cell transplantation. In addition, real-time PCR, immunohistochemistry, miRNA chip and mRNA chip are used to evaluate the effect of cell therapy.ResultsCompared with the POF group, the ovarian size and primordial follicle count in the hUC-MSC group were significantly improved, and the fertility was also significantly improved. Immunohistochemistry showed that compared with the POF group, the anti-Mullerian hormone and Ki-67 in the ovary of the hUC-MSC group increased significantly, and ovulation was significantly restored. Real-time PCR showed that the expression of follicle stimulating hormone receptor, inhibin and inhibin in the hUC-MSCs group was significantly restored compared with the POF group. The results of mRNA and miRNA chips also showed that hUC-MSC restored ovarian function at the gene level. long-term treatment effect shows that the multiple transplantation hUC-MSCs group is better than the single transplantation hUC-MSCs group. 60 days after the mice were injected with cyclophosphamide and busulfan, the organ coefficient of multiple transplantation of hUC-MSCs increased compared with the POF group, the number of primary follicles increased, and hormone secretion increased. ConclusionThe results show that multiple trasplantation of hUC-MSCs can promote the recovery of ovarian function in POF mice more than a single transplantation. This study provides a basis for the therapeutic dose and therapeutic effect of hUC-MSCs on POF.


Author(s):  
L. V. Tkachenko ◽  
I. A. Gritsenko ◽  
K. Yu. Tikhaeva ◽  
N. I. Sviridova ◽  
I. S. Gavrilova ◽  
...  

The problem of premature ovarian failure (POF) is currently in the spotlight of obstetricians and gynecologists worldwide. Early diagnosis of this pathology is necessary to prevent the development of serious pathological conditions. The systematization of modern ideas about laboratory and instrumental methods for POF diagnosing, assessing diagnostic value of parameters such as follicle stimulating hormone, anti-Mullerian hormone as well as the count of antral ovarian follicles, intraovarian blood flow and ovarian volume using ultrasound techniques, which can then be used as prognostic criteria for POF comprise a very important modality. Based on the findings obtained, early detection may lead to proposing new prognostic strategies.


1998 ◽  
Vol 70 (3) ◽  
pp. 565-567 ◽  
Author(s):  
Maria Beatriz da Fonte Kohek ◽  
Marcelo Cidade Batista ◽  
Alan J Russell ◽  
Keith Vass ◽  
Luciano Ricardo Giacaglia ◽  
...  

1993 ◽  
Vol 60 (5) ◽  
pp. 852-857 ◽  
Author(s):  
Lawrence C. Layman ◽  
Martha E. Shelley ◽  
Lee O. Huey ◽  
Sarah W. Wall ◽  
Sandra P.T. Tho ◽  
...  

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