scholarly journals Esculentoside A rescues granulosa cell apoptosis and folliculogenesis in mice with premature ovarian failure

Aging ◽  
2020 ◽  
Vol 12 (17) ◽  
pp. 16951-16962 ◽  
Author(s):  
Zhenteng Liu ◽  
Fenghua Li ◽  
Jingwen Xue ◽  
Meimei Wang ◽  
Shoucui Lai ◽  
...  
2018 ◽  
Vol 51 (5) ◽  
pp. 2341-2358 ◽  
Author(s):  
Xiaowei Nie ◽  
Youjin Dai ◽  
Yuan Zheng ◽  
Dan Bao ◽  
Qin Chen ◽  
...  

Background/Aims: This study investigated the effect of consecutive superovulation on the ovaries and established a premature ovarian failure (POF) model in mice. Methods: The mouse POF model was induced by 5-15 consecutive superovulation treatments with pregnant mare serum gonadotropin (PMSG), human chorionic gonadotropin (HCG) and prostaglandin F2α (PGF2α). Normal adult mice were compared with mice displaying natural ovarian aging. The following serum biochemical parameters were measured: including follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), estradiol (E2), inhibin B (INH B), malondialdehyde (MDA), total superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels. Follicles were counted using H&E staining. Levels of 8-hydroxyguanosine (8-OhdG), 4-hydroxynonenal (4-HNE), nitrotyrosine (NTY), anti-Mullerian hormone (AMH) and CDKN2A/ p16 (p16) were detected using immunohistochemical staining. Reactive oxygen species (ROS) levels were measured using dihydroethidium (DHE) staining. Cell apoptosis was detected using an in situ TUNEL fluorescence staining assay. Levels of proteins involved in ROS-related pathways and the p16 protein were detected using Western blotting. Sod1, Sod2 and Sod3 mRNA levels were detected using quantitative polymerase chain reaction (Q-PCR). Oocyte quality was evaluated using in vitro fertilization (IVF) and zygote culture. Results: Consecutive superovulation groups presented lower P, E2, SOD, GSH-Px and INH B levels, significantly higher FSH, LH, MDA and ROS levels, and significantly fewer primordial follicles compared with the control group. Consecutive superovulation groups presented significantly increased levels of Sod2, 8-OhdG, 4-HNE, NTY, significantly increased levels of the SIRT1 and FOXO1 proteins, significantly increased levels of the senescence-associated protein p16, as well as decreased AMH, Sod1 and Sod3 levels and increased granulosa cell apoptosis compared with the control group. Conclusion: Consecutive superovulation significantly decreased ovarian function and oocyte quality and increased oxidative stress and apoptosis in the ovary via a mechanism involving the p16 and SIRT1/FOXO1 signaling pathways. These findings suggest that consecutive superovulation may be used to establish a mouse model of ovarian aging.


2004 ◽  
Vol 18 (4) ◽  
pp. 953-967 ◽  
Author(s):  
Carolina J. Jorgez ◽  
Michal Klysik ◽  
Soazik P. Jamin ◽  
Richard R. Behringer ◽  
Martin M. Matzuk

Abstract Follistatin plays an important role in female physiology by regulating FSH levels through blocking activin actions. Failure to regulate FSH has been implicated as a potential cause of premature ovarian failure. Premature ovarian failure is characterized by amenorrhea, infertility, and elevated gonadotropin levels in women under the age of 40. Because follistatin is essential for postnatal viability, we designed a cre/loxP conditional knockout system to render the follistatin gene null specifically in the granulosa cells of the postnatal ovary using Amhr2cre transgenic mice. The follistatin conditional knockout females develop fertility defects, including reduced litter number and litter sizes and, in the most severe case, infertility. Reduced numbers of ovarian follicles, ovulation and fertilization defects, elevated levels of serum FSH and LH, and reduced levels of testosterone were observed in these mice. These findings demonstrate that compromising granulosa cell follistatin function leads to findings similar to those characterized in premature ovarian failure. Follistatin conditional knockouts may therefore be a useful model with which to further study this human syndrome. These studies are the first report of a granulosa cell-specific deletion of a gene in the postnatal ovary and have important implications for future endeavors to generate ovary-specific knockout mouse models.


Planta Medica ◽  
2015 ◽  
Vol 81 (11) ◽  
Author(s):  
M Wei ◽  
Y Lu ◽  
GB Mahady ◽  
D Liu ◽  
ZS Zheng

2021 ◽  
Author(s):  
CHETAN SAHNI ◽  
Rima DADA

Introduction: Premature Ovarian Failure (POF) being a heterogeneous genetic disease involves the interaction of multiple genetic defects and environmental factors and has been associated with several chromosomal abnormalities, single gene mutations, and genetic polymorphisms. BMP15 is a member of the transforming growth factor β (TGF-β) family. BMP15 gene product (protein) have 3 domians, mature domain (c-terminal region) of BMP15 binds to receptors located on granulosa cell surface to participate in key steps regarding ovarian function, such as granulosa cell proliferation and follicle maturation, ovulation rate modulation, oocyte competence determination and regulating granulosa cell sensitivity to FSH. Single nucleotide polymorphisms (SNPs) of the BMP-15 gene are associated with POF. Materials & Methods: 30 POF patients and 30 healthy age matched controls were recruited for cytogenetic and molecular analysis. 10 ml whole blood was collected for karyotyping and PCR and PCR was performed for known SNPs of BMP-15 gene (-9C>G, 538G>A, 788insTCT and 852C>T) respectively. Amplified PCR products were sequenced commercially. Observation/Result: Thirty cases (mean age 30 years) and thirty healthy controls (mean age 23 years) were recruited for the study. On cytogenetic analysis 2 cases had a 45, XO chromosomal complement. One case was heterozygous for the SNP (-9C>G) and one control was homozygous for the same SNP. Discussion: The prevalence of this SNP was about 10.7% in cases & 3.3% in healthy controls. This polymorphism in promoter region may cause altered expression of the gene and results in POF.


Sign in / Sign up

Export Citation Format

Share Document