Hypermethylation‐mediated downregulation of lncRNA PVT1 promotes granulosa cell apoptosis in premature ovarian insufficiency via interacting with Foxo3a

2021 ◽  
Author(s):  
Fang Wang ◽  
Xuemei Chen ◽  
Bo Sun ◽  
Yujia Ma ◽  
Wenbin Niu ◽  
...  
Keyword(s):  
Granulosa Cell ◽  
Cell Apoptosis ◽  
Premature Ovarian Insufficiency ◽  
Ovarian Insufficiency

scholarly journals Establishment and Mechanism Study of a Primary Ovarian Insufficiency Mouse Model using Lipopolysaccharide

2021 ◽  
Author(s):  
Si-Ji Lv ◽  
Shu-Hui Hou ◽  
Lei Gan ◽  
Jing Sun
Keyword(s):  
Mouse Model ◽  
Granulosa Cell ◽  
Cell Apoptosis ◽  
Low Dose ◽  
Ovarian Function ◽  
Histopathological Examination ◽  
Primary Ovarian Insufficiency ◽  
High Dose ◽  
Ovarian Insufficiency ◽  
Primordial Follicles

Abstract Background: This study aimed to establish a lipopolysaccharide (LPS)-induced primary ovarian insufficiency (POI) mouse model and to investigate the underlying mechanism.Methods: C57BL/6N female mice were intraperitoneally injected with low-dose LPS (0.5 mg/kg) once daily for 14 days, high-dose LPS (2.5 mg/kg) twice weekly for 2 weeks, and cyclophosphamide (CTX; 150 mg/kg) once weekly for 2 weeks. Ovarian function was assessed by measuring the length of the estrous cycle, the number of primordial follicles, and the levels of serum pituitary/ovarian hormones. Expression and production of interleukin 1β (IL-1β) were determined to evaluate ovarian inflammation. Histopathological examination was performed to examine ovarian fibrosis. TUNEL assay was carried out to evaluate granulosa cell apoptosis. Western blotting was performed to measure the levels of inflammation-, fibrosis-, and apoptosis-related proteins in mouse ovaries.Results: Like CTX, both low- and high-dose LPS administration significantly impaired ovarian functions in mice, as evidenced by extended lengths of estrous cycles, reduced counts of primordial follicles, and alterations in the levels of serum hormones. Also, LPS administration promoted granulosa cell apoptosis and ovarian fibrosis in mice. However, LPS but not CTX significantly promoted IL-1β expression and production in mice. Moreover, LPS treatment but not CTX significantly enhanced TLR, p-p65, p65, and MyD88 protein expression in mouse ovaries, suggesting that LPS differs from CTX in triggering ovarian inflammation. In general, continuous low-dose LPS stimulation was less potent than high-dose LPS stimulation in the above-mentioned effects.Conclusions: LPS induces ovarian inflammation, fibrosis, and granulosa cell apoptosis and can be used to establish a POI model in mice.

scholarly journals Establishment and Mechanism Study of a Primary Ovarian Insufficiency Mouse Model Using Lipopolysaccharide

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Si-Ji Lv ◽  
Shu-Hui Hou ◽  
Lei Gan ◽  
Jing Sun
Keyword(s):  
Mouse Model ◽  
Granulosa Cell ◽  
Cell Apoptosis ◽  
Low Dose ◽  
Histopathological Examination ◽  
Primary Ovarian Insufficiency ◽  
High Dose ◽  
Ovarian Insufficiency ◽  
Serum Hormones ◽  
Primordial Follicles

This study is aimed at establishing a lipopolysaccharide- (LPS-) induced primary ovarian insufficiency (POI) mouse model and investigating the underlying mechanism. C57BL/6N female mice were intraperitoneally injected with low-dose LPS (0.5 mg/kg) once daily for 14 days, high-dose LPS (2.5 mg/kg) twice weekly for 2 weeks, or cyclophosphamide (CTX; 150 mg/kg) once weekly for 2 weeks. Ovarian function was assessed by measuring the length of estrous cycle, the number of primordial follicles, and the levels of serum hormones. Expression and production of interleukin 1β (IL-1β) were determined to evaluate ovarian inflammation. Histopathological examination was performed to examine ovarian fibrosis. TUNEL assay was carried out to evaluate granulosa cell apoptosis. Western blotting was performed to measure the levels of inflammation-, fibrosis-, and apoptosis-related proteins in the mouse ovaries. Like CTX, both low- and high-dose LPS significantly impaired ovarian functions in mice, as evidenced by extended lengths of estrous cycles, reduced counts of primordial follicles, and alterations in the levels of serum hormones. Also, LPS promoted granulosa cell apoptosis and ovarian fibrosis in mice. However, LPS but not CTX promoted IL-1β expression and production in mice. Moreover, LPS but not CTX enhanced TLR, p-p65, p65, and MyD88 expression in mouse ovaries, suggesting that LPS differs from CTX in triggering ovarian inflammation. In general, continuous low-dose LPS stimulation was less potent than high-dose LPS to affect the ovarian functions. In conclusion, LPS may induce ovarian inflammation, fibrosis, and granulosa cell apoptosis and can be used to establish a POI model in mice.

Evidence for an FMR1 mRNA Gain-Of-Function Toxicity Mechanism in the Pathogenesis of Fragile-X Associated Premature Ovarian Insufficiency

2021 ◽  
Author(s):  
Roseanne Rosario ◽  
Hazel Stewart ◽  
Nila Roy Choudhury ◽  
Gracjan Michlewski ◽  
Nicolas Charlet-Berguerand ◽  
...  
Keyword(s):  
Granulosa Cell ◽  
Cell Model ◽  
Fragile X ◽  
Repeat Sequence ◽  
Premature Ovarian Insufficiency ◽  
Gain Of Function ◽  
Ovarian Insufficiency ◽  
Cgg Repeat ◽  
Function Mechanism

Abstract Fragile X-associated premature ovarian insufficiency (FXPOI) is caused by expansion of a CGG repeat sequence located in the 5’ untranslated region of the FMR1 gene. Women with FXPOI have a depleted ovarian reserve, resulting in amenorrhea, hypoestrogenism, and loss of fertility before the age of 40. FXPOI is caused by CGG sequence expansions to lengths between 55 and 200 repeats, known as a FMRI premutation, however the mechanism by which the premutation drives disease pathogenesis remains unclear. Two main hypotheses exist, which describe an mRNA toxic gain-of-function mechanism or that repeat-associated non-AUG (RAN) translation results in the production of an abnormal protein, called FMRpolyG. We have developed an in vitro granulosa cell model of the FMR1 premutation by ectopically expressing CGG-repeat RNA and FMRpolyG protein. We show that expanded CGG-repeat RNA accumulated in intranuclear RNA structures, and these aggregates were able to cause significant granulosa cell death independent of FMRpolyG expression. Furthermore, using an innovative RNA pulldown, mass spectrometry-based approach we have identified proteins that bind CGG-repeat RNA in granulosa cells in vitro, and thus may be deregulated as consequence of this interaction. Collectively, these data provide evidence for the contribution of an mRNA gain-of-function mechanism to FXPOI disease biology.

Menstrual cycle characteristics in women with premature ovarian insufficiency

2019 ◽  
Author(s):  
Miomira Ivovic ◽  
Ljiljana Marina ◽  
Milina Tancic-Gajic ◽  
Zorana Arizanovic ◽  
Magdalena Stankovic ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Premature Ovarian Insufficiency ◽  
Ovarian Insufficiency
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