Expression and activity of Rac1 is negatively affected in the dehydroepiandrosterone induced polycystic ovary of mouse

Maurya, Vineet Kumar; Chadchan, Sangappa B.; Kumar, Vijay; Mahfooz, Sahil; Singh, Abhishek; Rajender, Singh; Jha, Rajesh Kumar

doi:10.1186/1757-2215-7-32

Cited by 26 publications

(23 citation statements)

References 55 publications

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“…The Ras superfamily is the most common of small GTPases, which is further divided into subfamilies: RAS, RHO, RAB, RAP, ARF, RAN, RHEB, RAD and RIT. To date, RAS [ 18 , 19 ], RAC1 [ 20 ], RAB5B [ 21 ] and RAB8A [ 22 ] have been shown to be involved in the PCOS pathophysiology, but other GTPase-related members were not reported.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide DNA methylation and gene expression patterns provide insight into polycystic ovary syndrome development

et al. 2014

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Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. However, the epigenetic mechanism involved in PCOS progression remains largely unknown. Here, combining the DNA methylation profiling together with transcriptome analysis, we showed that (i) there were 7929 differentially methylated CpG sites (β > 0.1, P < 0.05) and 650 differential transcripts (fold change > 1.5, P < 0.005) in PCOS compared to normal ovaries; (ii) 54 genes were identified with methylated levels that were correlated with gene transcription in PCOS; and (iii) there were less hypermethylated sites, but many more hypomethylated sites residing in CpG islands and N_Shore in PCOS. Among these genes, we identified that several significant pathways, including the type I diabetes mellitus pathway, p53 signaling pathway and NOD-like receptor signaling pathway, and some immune and inflammatory diseases may be highly involved in PCOS development. These results suggested that differences in genome-wide DNA methylation and expression patterns exist between PCOS ovaries and normal ovaries; epigenetic mechanisms may in part be responsible for the different gene expression and PCOS phenotype. All of this may improve our understanding of the basic molecular mechanism underlying the development of PCOS.

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Section: Discussionmentioning

confidence: 99%

Genome-wide DNA methylation and gene expression patterns provide insight into polycystic ovary syndrome development

et al. 2014

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“…To examine ovarian morphology, every 12th section was mounted on a glass slide. Numbers of corpora lutea and large antral follicles were counted [ 28 , 29 ]. The follicle diameter was calculated as the mean distance between opposite basal membrane portions, while the wall thickness was calculated as the sum of theca interna and granulosa cell layers.…”

Section: Methodsmentioning

confidence: 99%

The effect of cinnamon on polycystic ovary syndrome in a mouse model

Dou

Zheng

et al. 2018

Reprod Biol Endocrinol

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BackgroundPolycystic ovary syndrome (PCOS) is the most prevalent cause of anovulatory infertility and hyperandrogenism. Evidence favors insulin resistance and compensatory hyperinsulinemia as the predominant, perhaps primary, defects in PCOS. The use of insulin-sensitizing drugs has been shown to improve both the reproductive and the metabolic aspects of PCOS. Cinnamon has been found to have insulin sensitizing effect and improve menstrual cyclicity in women with PCOS. The aim of this study was to determine the effect and mechanism of cinnamon on PCOS using a dehydroepiandrosterone (DHEA) induced PCOS mouse model.MethodsPrepubertal C57BL/6 mice (age 25 days) were raised to developed into control group, DHEA group and DHEA plus cinnamon group for 20 days. The stages of the estrous cycle were determined based on vaginal cytology; metabolic characteristics were examined by intraperitoneal glucose tolerance test and insulin tolerance test, the serum levels of hormones (testosterone, insulin, LH, FSH, IGF-1, IGFBP-1) were checked using enzyme-linked immunosorbent assay (ELISA) method, the ovarian morphology was observed by stained with hematoxylin and eosin. IGF-1 and IGFBP-1 expression in ovary were detected by immunohistochemical stain.ResultsCinnamon restores the cyclicity and ovary morphology in PCOS mice model induced by DHEA. There are significant differences of serum level of total testosterone (0.033 ± 0.009 ng/ml), among control group, DHEA and cinnamon group (0.052 ± 0.011 ng/ml), and DHEA group (0.079 ± 0.015 ng/ml); There was an increasing tendency of serum FSH level from DHEA group (5.02 ± 0.31 ng/ml), DHEA and cinnamon group (5.81 ± 0.51 ng/ml), to control group (7.13 ± 0.74 ng/ml); and there was a decreasing trend of serum LH level from DHEA group (3.75 ± 0.57 ng/ml), DHEA and cinnamon group (1.35 ± 0.61 ng/ml), or control group (0.69 ± 0.34 ng/ml); serum insulin level is significantly higher in DHEA treated mice (1.61 ± 0.31 ng/ml) than control group (0.93 ± 0.19 ng/ml), or DHEA and cinnamon effect (1.27 ± 0.23 ng/ml) (p < 0.05). The DHEA group also has a higher serum IGF-1 level (0.35 ± 0.06 ng/ml) than control group (0.17 ± 0.04 ng/ml) or DHEA and cinnamon group (0.21 ± 0.05 ng/ml) (p < 0.05). While DHEA group has a lower IGFBP-1 level (5.5 ± 1.6 ng/ml) than control group (15.8 ± 2.1 ng/ml) or DHEA and cinnamon group (10.3 ± 2.5 ng/ml) (p < 0.05). Cinnamon also attenuates DHEA induced a higher IGF-1 and lower IGFBP-1 expression in ovary by immunohistochemistry.ConclusionsThese preliminary data suggest that cinnamon supplementation improves insulin resistance and may be a potential therapeutic agent for the treatment of PCOS.

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“…Furthermore, both progesterone and oestradiol of PCOS mice were increased dramatically (P < 0.001 and P < 0.01, respectively) as compared with the normal mice ( Figure 2C). 37 29 Furthermore, hyperandrogenism increased plasma concentrations of oestradiol, after the increase in the number of dormant follicles, together with the breakdown of later stages of follicle development and subsequently anovulation.…”

Section: Hormonal Assays Of Pcos Modelmentioning

confidence: 99%

Improvement of oocyte in vitro maturation from mice with polycystic ovary syndrome by human mesenchymal stromal cell–conditioned media

Jafarzadeh

Nazarian

Novin

et al. 2018

J of Cellular Biochemistry

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The outcome of in vitro maturation (IVM) in the patients with polycystic ovary syndrome (PCOS) is poor. Abnormal intraovarian paracrine interplay alters microenvironment for oocyte development through folliculogenesis and decreases developmental competence of oocytes in patients with PCOS. Mesenchymal stromal cells (MSCs) secrete a variety of cytokines and growth factors that could promote oocyte maturation in vitro. Thus, in the current study we aimed to evaluate the effect of human bone marrow MSC-conditioned media (hBM-MSC-CM), as a supplement, to enrich IVM medium for PCOS germinal vesicles (GVs). For this purpose, oocytes at GV and metaphase II (MII) stages were harvested from PCOS mice. The GVs were randomly divided into four groups and incubated for 24 hours in an IVM medium (TCM199, as the control group) or TCM199 supplemented by 25%, 50%, and 75% of hBM-MSC-CM (PCOS-CM25, PCOS-CM50, and PCOS-CM75 groups, respectively) so as to evaluate which dose(s) could enhance maturation rate of the GVs and their subsequent in vitro fertilization (IVF) outcome. Furthermore, MII oocytes and their subsequent IVF outcome were considered as the in vivo matured (PCOS-IVO) group. The data showed that supplementation of IVM medium with 50% hBM-MSC-CM significantly increased cytoplasmic and nuclear maturation of the GVs (P < 0.001), and also fertilization and two-cell rate (P < 0.001) and blastocyst formation (P < 0.01) of in vitro matured oocytes from mice with PCOS. Overall, higher oocyte maturation and fertilization outcome in PCOS-CM50 group proposed that enrichment of IVM medium with hBM-MSC-CM could be considered as a promising approach to improve IVM of PCOS oocytes.

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Expression and activity of Rac1 is negatively affected in the dehydroepiandrosterone induced polycystic ovary of mouse

Cited by 26 publications

References 55 publications

Genome-wide DNA methylation and gene expression patterns provide insight into polycystic ovary syndrome development

Genome-wide DNA methylation and gene expression patterns provide insight into polycystic ovary syndrome development

The effect of cinnamon on polycystic ovary syndrome in a mouse model

Improvement of oocyte in vitro maturation from mice with polycystic ovary syndrome by human mesenchymal stromal cell–conditioned media

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