Metformin improves epigenetic modification involved in oocyte growth and embryo development in polycystic ovary syndrome mice model

Author(s):  
Showra Amani Abkenari ◽  
Leili Safdarian ◽  
Fardin Amidi ◽  
Ali Hosseini ◽  
Roya Aryanpour ◽  
...  
2006 ◽  
Vol 91 (7) ◽  
pp. 2789-2791 ◽  
Author(s):  
T. E. Hickey ◽  
R. S. Legro ◽  
R. J. Norman

Abstract Context: The cause of polycystic ovary syndrome (PCOS) is unknown, although genetic and environmental influences are clearly implicated. Some genetic studies have suggested the involvement of X-linked genes in PCOS, but the influence of X chromosome inactivation (XCI) on manifestation of this disorder has not previously been examined. Objective: The objective of the study was to test the null hypothesis that XCI has no influence on clinical presentation of PCOS. Design: We examined patterns of XCI between sister pairs with the same genotype at a polymorphic locus on the X chromosome in families with PCOS. Setting: The study was conducted at a private practice. Participants: PCOS was defined as hyperandrogenemia with chronic anovulation. Forty families were studied in which DNA was obtained from at least one parent, the proband, and one sister that could be accurately diagnosed as being affected or unaffected. Main Outcome Measure(s): Relative expression of two X-linked alleles was determined, and the ratio of one to the other represented the pattern of XCI. Results: The statistical odds on a different clinical presentation between sisters was approximately 29 times higher in sister pairs with different patterns of XCI, compared with sister pairs with the same pattern of XCI (odds ratio 28.9; 95% confidence interval 4.0–206; P = 0.0008). Conclusions: This study provides evidence to refute the null hypothesis and propose a closer inspection of X-linked genes in PCOS, one in which both genotype and epigenotype are considered. Environmental determinants of PCOS may alter clinical presentation via epigenetic modifications, which currently remain undetected in traditional genetic analyses.


Reproduction ◽  
2019 ◽  
Vol 158 (1) ◽  
pp. R27-R40 ◽  
Author(s):  
Edgar Ricardo Vázquez-Martínez ◽  
Yadira Inés Gómez-Viais ◽  
Elizabeth García-Gómez ◽  
Christian Reyes-Mayoral ◽  
Enrique Reyes-Muñoz ◽  
...  

Polycystic ovary syndrome (PCOS) is the leading endocrine and metabolic disorder in premenopausal women characterized by hyperandrogenism and abnormal development of ovarian follicles. To date, the PCOS etiology remains unclear and has been related to insulin resistance, obesity, type 2 diabetes mellitus, cardiovascular disease and infertility, among other morbidities. Substantial evidence illustrates the impact of genetic, intrauterine and environmental factors on the PCOS etiology. Lately, epigenetic factors have garnered considerable attention in the pathogenesis of PCOS considering that changes in the content of DNA methylation, histone acetylation and noncoding RNAs have been reported in various tissues of women with this disease. DNA methylation is changed in the peripheral and umbilical cord blood, as well as in ovarian and adipose tissue of women with PCOS, suggesting the involvement of this epigenetic modification in the pathogenesis of the disease. Perhaps, these defects in DNA methylation promote the deregulation of genes involved in inflammation, hormone synthesis and signaling and glucose and lipid metabolism. Research on the role of DNA methylation in the pathogenesis of PCOS is just beginning, and several issues await investigation. This review aims to provide an overview of current research focused on DNA methylation and PCOS, as well as discuss the perspectives regarding this topic.


Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 279
Author(s):  
Tiange Li ◽  
Yue Zhang ◽  
Jiajia Song ◽  
Lijun Chen ◽  
Min Du ◽  
...  

The effects of synbiotic yogurt supplemented with inulin on the pathological manifestations and gut microbiota–bile acid axis were investigated using a dehydroepiandrosterone (DHEA)-induced polycystic ovary syndrome (PCOS) mice model. Female C57BL/6J mice were injected subcutaneously with DHEA at a dose of 6 mg/100 g BW for 20 days to establish a PCOS mouse model. Then, the PCOS mice were treated with yogurt containing inulin (6% w/w) at 15 mL/kg BW for 24 days. Results showed that supplementation of synbiotic yogurt enriched with inulin to PCOS mice decreased the body weight gain, improved estrus cycles and ovary morphology, and reduced the levels of luteinizing hormone while increasing the levels of follicle-stimulating hormone and interleukin-22 in serum. At the genus level, synbiotic yogurt increased the relative abundance of Lactobacillus, Bifidobacterium, and Akkermansia. PICRUSt analysis indicated that KEGG pathways including bile acid biosynthesis were changed after inulin-enriched synbiotic yogurt supplementation. Synbiotic yogurt enriched with inulin also modulated the bile acid profiles. In conclusion, inulin-enriched synbiotic yogurt alleviated reproductive dysfunction and modulated gut microbiota and bile acid profiles in PCOS mice.


Author(s):  
Fatemeh Eini ◽  
Khojasteh Joharchi ◽  
Maryam Azizi Kutenaei ◽  
Pegah Mousavi

Background: Nigella Sativa (NS) and its active component, thymoquinone, have beneficial protective effects on experimental animal models of polycystic ovary syndrome (PCOS) and different human diseases. Objective: The present study aimed to investigate the effects of NS hydro-alcoholic extract (NSE) on the oocyte quality of PCOS mice during in vitro maturation. Materials and Methods: For induction of PCOS, 40 prepubertal 21-days old female B6D2F1 mice (18-22 g body weight) received subcutaneous dehydroepiandrosterone daily. After validation of the model, germinal vesicle-stage oocytes of superovulated mice were collected and placed in the culture medium containing different concentrations (0, 1, 50, and 100 μg/ml) of NSE. For the measurement of developmental competency, some mature oocytes were fertilized with epididymal spermatozoa. Other mature oocytes were assessed for oxidative stress. Also, some mRNA expression levels involved in oocyte maturation and epigenetic modification were evaluated. Results: The 50 μg/ml NSE treated group showed significantly higher r ates o f maturation, f ertilization, and blastocyst formation in comparison with both control and PCOS groups. A high level of glutathione concentration and glutathione peroxidase mRNA expression, besides a low level of reactive oxygen species content all, were observed in oocytes treated with 50 μg/ml NSE, indicating the modification of oxidative statue. Furthermore, the oocytes in the 50 μg/ml-treated group showed an upregulation of mRNA expression in epigenetic-related genes (Dnmt1 and Hdac1) and maternally derived genes (Mapk and Cdk1), correspondingly downregulation of cyclooxygenase2 mRNA expression, in comparison to other groups. Conclusion: The results of this study indicated that 50 μg/ml NSE improves oocyte maturation, oxidative statues and epigenetic modifications. These may be the all reasons for the developmental competency in the control and PCOS mice oocytes. Key words: Epigenetic modification, In-vitro maturation, Nigella sativa, Oxidative stress, Polycystic ovary syndrome. Key words: Epigenetic modification, In-vitro maturation, Nigella sativa, Oxidative stress, Polycystic ovary syndrome. Key words: Epigenetic modification, In-vitro maturation, Nigella sativa, Oxidative stress, Polycystic ovary syndrome.


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