Ginsenoside Rg1 attenuates premature ovarian failure of D-gal induced POF mice through downregulating p16INK4a and upregulating SIRT1 expression

2021 ◽  
Vol 21 ◽  
Author(s):  
Xiao-Hu Liu ◽  
Shi-Zhong Cai ◽  
Yue Zhou ◽  
Ya-Ping Wang ◽  
Yan-Jun Han ◽  
...  
Keyword(s):  
Growth Rate ◽  
Corpus Luteum ◽  
Premature Ovarian Failure ◽  
Weight Coefficient ◽  
Ovarian Failure ◽  
Ovarian Weight ◽  
Sirt1 Expression ◽  
Weight Growth ◽  
Phosphate Buffered Saline ◽  
Type Information

Background: Premature ovarian failure (POF) refers to pathological amenorrhea before 40 years. Aim/Objective: To explore regulatory effect of Rg1 on POF and clarify associated mechanisms. Materials and methods: POF mice were induced by injecting with D-galactose (D-gal, 200 mg/kg/day). Mice were divided into phosphate buffered saline (PBS), D-gal (POF mice), D-gal/Rg1 group (POF mice administrating D-gal/Rg1). Weight growth rate and ovarian weight coefficient were measured. Serum estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH), superoxide dismutase (SOD), catalase (CAT) levels were examined using ELISA. Status of follicle and corpus luteum was determined using hematoxylin-eosin (HE) staining. P16INK4a and silent-mating type information regulation-2 homolog-1 (SIRT1) was determined using western blotting and RT-PCR. Findings: Weight growth rate and ovarian weight coefficient of mice in D-gal group were significantly decreased than PBS group (p<0.05). Serum E2, LH, SOD, CAT levels were significantly decreased, FSH levels were remarkably increased in D-gal group than PBS group (p<0.05). Rg1 (D-gal/Rg1 group) significantly increased weight growth rate and ovarian weight coefficient, enhanced E2, LH, SOD, CAT levels and decreased FSH levels than D-gal group (p<0.05). HE staining demonstrated normal follicle morphology/structure of mice in PBS group and decreased number of follicles, obvious vacuolation of corpus luteum and increased atretic follicles of mice in D-gal group. Compared with D-gal group, number of follicles was increased, luteal follicles was decreased of mice in D-gal/Rg1 group (p<0.05). Rg1 significantly (D-gal/Rg1) downregulated p16INK4a and upregulated SIRT1 expression in ovarian tissues of mice compared to D-gal group (p<0.05). Conclusions: Rg1 could delay premature ovarian failure in D-gal induced POF mouse model through downregulating p16INK4a and upregulating SIRT1 expression.

scholarly journals A new heterozygous mutation of the FOXL2 gene is associated with a large ovarian cyst and ovarian dysfunction in an adolescent girl with blepharophimosis/ptosis/epicanthus inversus syndrome

2005 ◽  
Vol 153 (3) ◽  
pp. 353-358 ◽  
Author(s):  
K Raile ◽  
H Stobbe ◽  
R B Tröbs ◽  
W Kiess ◽  
R Pfäffle
Keyword(s):  
Corpus Luteum ◽  
Premature Ovarian Failure ◽  
Adolescent Girl ◽  
Ovarian Failure ◽  
Clinical Aspects ◽  
Type I ◽  
Type Ii ◽  
Ovarian Dysfunction ◽  
Corpus Luteum Cyst ◽  
Large Corpus

Blepharophimosis/ptosis/epicanthus inversus syndrome (BPES), an autosomal dominant syndrome in which eyelid malformation is associated with (type I BPES) or without premature ovarian failure (type II BPES). Mutations of a putative winged helix/forkhead transcription factor FOXL2 account for both types of BPES. We report on a 16-year-old adolescent girl with blepharophimosis and ptosis. Subsequently she developed oligomenorrhea, secondary amenorrhea for 6 months, and an extremely large cyst of one ovary. The cyst contained 8 l of cyst fluid and histopathology displayed a large corpus luteum cyst. Following laparotomy, gonadotropin levels were elevated (LH 17.2 U/l, FSH 29.4 U/l) and estradiol levels decreased (67 pmol/l). Because of clinical aspects of BPES and abnormal ovarian function we suspected a mutation of her FOXL2 gene and found a new in-frame mutation (904_939dup36) on one allele, leading to a 12 alanine expansion within the polyalanine domain. We conclude that the FOXL2 mutation 904_939dup36 may account not only for blepharophimosis and ptosis but also for ovarian dysfunction and growth of the large corpus luteum cyst. In contrast to known FOXL2 mutations with polyalanine expansions and association with BPES type II, clinical aspects of our girl may indicate some degree of ovarian dysfunction that might finally lead to BPES type I with premature ovarian failure.

scholarly journals Premature ovarian failure: morphological and ultrastructural aspects

1994 ◽  
Vol 112 (2) ◽  
pp. 534-538 ◽  
Author(s):  
Mauro Abi Haidar ◽  
Edmund Chada Baracat ◽  
Manuel de Jesus Simões ◽  
Gustavo Rubino de Azevedo Focchi ◽  
Joaquim Evêncio Neto ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Connective Tissue ◽  
Corpus Luteum ◽  
Premature Ovarian Failure ◽  
Ovarian Follicles ◽  
Ovarian Failure ◽  
Primordial Follicles ◽  
Dense Connective Tissue ◽  
Transmission Electron

The authors documented by means of light and transmission electron microscopy that the ovaries of women with premature ovarian failure (POF) displayed dense connective tissue and rare corpora albicantia. Eight of the ten studied cases did not present ovarian follicles; in two cases, it was verified the presence of ovarian follicles, atypical primordial follicles and in one case, a corpus luteum was identified (after stimulation with exogenous gonadotrophin). Regarding the ultrastructural analysis, it was noted that the fibroblasts were united one to each other by cellular prolongations that formed a woof, constituting a cellular syncicius.

EPIGENETIC ALTERATIONS ASSOCIATED WITH PREMATURE OVARIAN FAILURE

2008 ◽  
Vol 31 (4) ◽  
pp. 11
Author(s):  
Manda Ghahremani ◽  
Courtney W Hannah ◽  
Maria Peneherrera ◽  
Karla L Bretherick ◽  
Margo R Fluker ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Premature Ovarian Failure ◽  
Promoter Region ◽  
Gene Promoter ◽  
Ovarian Failure ◽  
P Value ◽  
Epigenetic Alterations ◽  
Methylation Array ◽  
Cpg Sites ◽  
Deficient Mice

Background/Purpose: Premature ovarian failure (POF) affects 1% of women with a largely idiopathic and poorly understood etiology. The objective of this study was to identify specific epigenetic alterations by measuring DNA methylation of gene regulatory regions in women with POF vs. controls. Methods: Blood samples were collected from idiopathic POFpatients (Amenorrhea for at least 3 months and 2 serum FSH levels of > 40mIU/ml obtained > 1 month apart prior to age 40) and control women (CW) (healthy pregnancy after age 37 with out a pregnancy loss). Genomic DNA was extracted from EDTA anticoagulated blood and bisulfite converted for analysis using the Illumina Golden Gate Methylation Panel which measures DNA methylation at 1506 CpG sites in the promoter regions of 807 genes in 10 POF and 12 CW. Candidate genes with altered epigenetic marks between POF and CW at a nominal P-value < 0.05 were identified using a t-testcomparison within the Illumina bead studio software. Genes of interest were further analyzed for quantitative methylation at specific CpG sites using pyrosequencing in 30 POF and 30 CW. Results: Comparison of DNA methylation profiles of our initial POF and CW groups identified several genes with statistically significanthyper- or hypo- methylation in the POF group (P < 0.05), including the Androgen Receptor (AR)promoter region, which was significantly hypermethylated. To further validate these results, DNA methylation of the AR gene promoter was quantified bypryosequencing in a larger group of POF and CW. Pyrosequencing further confirmed a significantly higher DNA methylation of the AR promoter region inPOF vs. CW (P=0.007). Conclusions: This is a novel study identifying epigenetic alterations in POF. The hypermethylation of the AR gene in POF patients may cause decreased level of the AR in these women. This is especially interesting given a recent report of induced POF in AR deficient mice^1. Specific epigenetic markers, as identified by DNA methylation array profiling in blood, may serve as useful biomarkers for POF and other fertility disorders. However, it will need to be determined if these methylation changes are present prior to diagnosis, or are a consequence of menopause itself. Reference: 1.Hiroko S. et al. Premature ovarian failure in androgenreceptor deficient mice. PNAS;103:224-9

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