scholarly journals Inhibition of the NLRP3 inflammasome prevents ovarian aging

2020 ◽  
Author(s):  
José M. Navarro-Pando ◽  
Elísabet Alcocer-Gómez ◽  
Beatriz Castejón-Vega ◽  
Jordi Muntané ◽  
Pedro Bullon ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Ovarian Tissue ◽  
Female Fertility ◽  
Reproductive Aging ◽  
Ovarian Insufficiency ◽  
Ovarian Aging ◽  
Age Dependent ◽  
Estradiol Levels ◽  
Hormonal Levels

Inflammation is a hallmark of many processes during aging and reproductive physiology, negatively affecting female fertility. The goal of this study was to evaluate the role of the NLRP3 inflammasome in ovarian aging and female fertility. Age-dependent increased expression of NLRP3 in the ovary was observed in female WT mice during reproductive aging. High expression of NLRP3, caspase 1 and IL-1β was also observed in granulosa cells from patients with primary ovarian insufficiency. Ablation of the NLRP3 inflammasome improved the survival and pregnancy rates in mice, increased hormonal levels of AMH, a biochemical marker of ovarian reserve, and autophagy rates in ovarian tissue. Deficiency of the NLRP3 inflammasome also reduced serum FSH and estradiol levels. Consistent with these results, pharmacological inhibition of NLRP3 using a direct NLRP3 inhibitor, MCC950, improved fertility in female mice to levels comparable to those of Nlrp3−/− mice. These results suggest that the NLRP3 inflammasome is implicated in the age-dependent loss of female fertility and position this inflammasome as a potential new therapeutic target for the treatment of infertility.

scholarly journals Inhibition of the NLRP3 inflammasome prevents ovarian aging

2021 ◽  
Vol 7 (1) ◽  
pp. eabc7409
Author(s):  
José M. Navarro-Pando ◽  
Elísabet Alcocer-Gómez ◽  
Beatriz Castejón-Vega ◽  
Elena Navarro-Villarán ◽  
Mónica Condés-Hervás ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Nlrp3 Inflammasome ◽  
Therapeutic Target ◽  
Female Fertility ◽  
Reproductive Aging ◽  
Ovarian Insufficiency ◽  
Ovarian Aging ◽  
Age Dependent ◽  
Estradiol Levels

Inflammation is a hallmark of aging and is negatively affecting female fertility. In this study, we evaluate the role of the NLRP3 inflammasome in ovarian aging and female fertility. Age-dependent increased expression of NLRP3 in the ovary was observed in WT mice during reproductive aging. High expression of NLRP3, caspase-1, and IL-1β was also observed in granulosa cells from patients with ovarian insufficiency. Ablation of NLRP3 improved the survival and pregnancy rates and increased anti-Müllerian hormone levels and autophagy rates in ovaries. Deficiency of NLRP3 also reduced serum FSH and estradiol levels. Consistent with these results, pharmacological inhibition of NLRP3 using a direct NLRP3 inhibitor, MCC950, improved fertility in female mice to levels comparable to those of Nlrp3−/− mice. These results suggest that the NLRP3 inflammasome is implicated in the age-dependent loss of female fertility and position this inflammasome as a potential new therapeutic target for the treatment of infertility.

scholarly journals Mitochondrial Dysfunction and Ovarian Aging

Endocrinology ◽  
2020 ◽  
Vol 161 (2) ◽  
Author(s):  
Işıl Kasapoğlu ◽  
Emre Seli
Keyword(s):  
Mitochondrial Dysfunction ◽  
Ovarian Reserve ◽  
Reproductive Aging ◽  
Ovarian Dysfunction ◽  
Ongoing Research ◽  
Ovarian Aging ◽  
Age Related ◽  
Age Related Changes

Abstract As women delay childbearing because of demographic and socioeconomic trends, reproductive aging and ensuing ovarian dysfunction become increasingly more prevalent causes of infertility. Age-related decline in fertility is characterized by both quantitative and qualitative deterioration of the ovarian reserve. Importantly, disorders of aging are frequently associated with mitochondrial dysfunction, as are impaired oogenesis and embryogenesis. Ongoing research explores the role of mitochondrial dysfunction in ovarian aging, and potential ways to exploit mitochondrial mechanisms to slow down or reverse age-related changes in female gonads.

scholarly journals Anti-Mullerian hormone and polycystic ovary syndrome

2013 ◽  
Vol 62 (6) ◽  
pp. 55-61
Author(s):  
Igor Pavlovich Nikolaenkov ◽  
Vladimir Vsevolodovich Potin ◽  
Marina Anatol’evna Tarasova
Keyword(s):  
Literature Review ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Ovarian Tissue ◽  
Biological Properties ◽  
Ovary Syndrome ◽  
Ovarian Insufficiency

Polycystic ovary syndrome (PCOS) is the most common form of normogonadotropic ovarian insufficiency, hyperandrogenaemy and anovulation sterility. One of the probable causes of this disease is disturbance of folliculogenesis, which is accompanied by overproduction of anti-Mullerian hormone (AMH) by ovarian tissue. There is a literature review about structure, biological properties and the role of AMH in pathogenesis of PCOS in this article.

scholarly journals BRCA1, BRCA2 and primary ovarian insufficiency

2020 ◽  
Vol 165 ◽  
pp. 05009
Author(s):  
Yinuo Zhang
Keyword(s):  
Primary Ovarian Insufficiency ◽  
Dna Breaks ◽  
Brca1 And Brca2 ◽  
Dsb Repair ◽  
Ovarian Insufficiency ◽  
Ovarian Aging ◽  
Brca Genes ◽  
Mutation Carriers ◽  
Increased Risk

BRCA1 and BRCA2 genes belong to the family of ataxia-telangiectasia-mutated (ATM)-mediated DNA DSB repair genes that play a critical role in the DNA double-strand break (DSB) repair. Mutations in BRCA genes significantly increase the lifetime risk of breast, ovarian, fallopian tube and primary peritoneal cancers. In addition to the increased risk for multiple malignancies, recent literature suggest that mutations in BRCA genes could lead to decreased ovarian reserve and subsequent ovarian aging. In this review, we will focus on role of BRCA1 and BRCA2 in ovarian function, particularly ovarian aging and primary ovarian insufficiency. Serum AMH values are generally lower in BRCA1 mutation carriers but not in BRCA2 mutation carriers. BRCA2 carriers were more likely to have chemotherapy-induced amenorrhea DNA not stable, linking with ovarian aging. The mechanism by which BRCAs mutation in the pathogenesis of POI is the inpaired function of repairing DNA breaks. Future studies investigating the knockout models to elucidate the role of the BRCAs genes in ovarian development and oocyte maturation will be interesting.

ANDROST-5-ENE-3β,17β-DIOL IN OVARY OF POST-MENOPAUSAL HYPEROESTROGENIC WOMEN

1968 ◽  
Vol 58 (3) ◽  
pp. 364-376 ◽  
Author(s):  
S. Pesonen ◽  
M. Ikonen ◽  
B-J. Procopé ◽  
A. Saure
Keyword(s):  
Ovarian Tissue ◽  
Cortical Layer ◽  
Vaginal Smears ◽  
Incubation Experiments ◽  
Cell Groups ◽  
Post Menopause ◽  
Reducing Activity ◽  
Post Menopausal ◽  
One Year

ABSTRACT The ovaries of ten patients, at least one year after the post-menopause, were incubated with two Δ5-C19-steroids and also studied histochemically. All these patients had post-menopausal uterine bleeding and increased oestrogen excretion of the urine. The urinary estimations of gonadotrophins, 17-KS, 17-OHCS and pregnanediol were carried out on all patients. Vaginal smears were read according to Papanicolaou, and the endometrium and ovaries were studied histologically. The incubation experiments indicate the presence of Δ5-3β-hydroxysteroid-dehydrogenase. When androst-5-ene-3β,17β-diol was used as precursor the formation of testosterone occurred without any concomitant production of DHA and/or androstenedione. This seems to indicate the possible role of the Δ5-pathway in the formation of testosterone by post-menopausal ovarian tissue. The histochemical reactions indicated a reducing activity on NADH, lactate and glucose-6-phosphate, in certain corpora albicantia, atretic follicles and in diffuse thecoma regions in the cortical layer of the ovary. Steroid-3β-ol-dehydrogenase and β-hydroxybutyrate-dehydrogenase were found only at the edges of certain corpora albicantia, in some individual stroma cell groups and in some atretic follicles. Our studies, both biochemical and histochemical, suggest that the observed increase in the urinary oestrogens of the patients studied might in part at least, be of ovarian origin. This opinion is also supported by the postoperative oestrogen values.

Understanding the role of Inflammasome in Angina Pectoris

2020 ◽  
Vol 21 ◽  
Author(s):  
Ishita Sharma ◽  
Tapan Behl ◽  
Simona Bungau ◽  
Monika Sachdeva ◽  
Arun Kumar ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Angina Pectoris ◽  
Nlrp3 Inflammasome ◽  
Vital Role ◽  
Death Process ◽  
Cell Death Process ◽  
Artery Disease ◽  
Species Production ◽  
Pro Inflammatory Cytokines

Abstract:: Angina pectoris, associated with coronary artery disease, a cardiovascular disease where, pain is caused by adverse oxygen supply in myocardium, resulting in contractility and discomfort in chest. Inflammasomes, triggered by stimuli due to infection and cellular stress have identified to play a vital role in the progression of cardiovascular disorders and thus, causing various symptoms like angina pectoris. Nlrp3 inflammasome, a key contributor in the pathogenesis of angina pectoris, requires activation and primary signaling for the commencement of inflammation. Nlrp3 inflammasome elicit out an inflammatory response by emission of pro inflammatory cytokines by ROS (reactive oxygen species) production, mobilization of K+ efflux and Ca2+ and by activation of lysosome destabilization that eventually causes pyroptosis, a programmed cell death process. Thus, inflammasome are considered to be one of the factors involved in the progression of coronary artery diseases and have an intricate role in development of angina pectoris.

scholarly journals Flavonoids Ameliorate Stress-Induced Depression by Preventing NLRP3 Inflammasome Priming

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1231-1231
Author(s):  
Giulio Pasinetti
Keyword(s):  
Mrna Expression ◽  
Chronic Stress ◽  
Nlrp3 Inflammasome ◽  
Signaling Cascades ◽  
Dietary Polyphenols ◽  
Funding Sources ◽  
Glycation End Products ◽  
Molecular Patterns

Abstract Objectives Chronic stress activates danger-associated molecular patterns (DAMPs), stimulating the NLRP3 inflammasome. NLRP3 activation triggers the release of pro-inflammatory cytokine IL-1β. The activity of the NLRP3 inflammasome propagates pro-inflammatory signaling cascades implicated in the onset of depression. Our previous studies show that polyphenolic compounds were found to ameliorate stress induced depression in mouse models. However, the relevant mechanism has not been identified. This study examined the effect of administering polyphenols on DAMP signaling in enriched mice microglia. Methods This study examined the effect of administering polyphenols on DAMP signaling in mice microglia. To recapitulate stress-induced depression, mice underwent chronic unpredictable stress (CUS). Microglia were isolated at various time points throughout the CUS protocol. We also assessed long-term persistent changes after CUS and susceptibility to subthreshold unpredictable stress (US) re-exposure. Results Interestingly, the development of US – induced depression and anxiety depended upon a previous exposure to CUS. We found that CUS caused robust upregulation of IL-1β mRNA in enriched microglia, an effect that persists for up to 4 weeks following CUS exposure. Following the subthreshold US re-exposure, we observed the upregulation of pro- IL-1β as well as pro-receptor for advanced glycation end products (RAGE). Toll-like receptor 4 (TLR-4) was not. We also observed an increase in RAGE mRNA expression when mice were exposed to US prior to the start of the CUS paradigm. Importantly, a primary exposure to US, was sufficient to increase RAGE mRNA expression. We found that polyphenol administration significantly improved CUS-induced depressive-like phenotypes and also reversed neuroinflammation in mice. Treatment with dietary flavonoids prevented upregulation of IL-1β, RAGE mRNA, which reflects the ability of polyphenols that may have begun following the primary exposure to US. Conclusions Taken all together, the results provide evidence of the role of dietary polyphenols in preventing persistent microglial activation, which has been shown to result in reduced long term vulnerability to depressive-like behaviors following expose to chronic stress. Funding Sources This study was supported by a P50 CARBON Center grant from the NCCIH/ODS.

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