Low dose spironolactone-mediated androgen-adiponectin modulation alleviates endocrine-metabolic disturbances in letrozole-induced PCOS

Olaniyi, Kehinde S.; Oniyide, Adesola A.; Adeyanju, O.; Ojulari, Lekan Sheriff; Omoaghe, Adams O.; Olaiya, Oluranti

doi:10.1016/j.taap.2020.115381

Cited by 27 publications

(18 citation statements)

References 57 publications

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“…Rats were maintained under standard environmental conditions of temperature (22–26°C), relative humidity (50–60%), and 12-hour dark/light cycle. Polycystic ovarian syndrome was experimentally induced by administering letrozole (1 mg/kg) once daily for 21 days as previously reported [ 8 , 26 – 28 ].…”

Section: Methodsmentioning

confidence: 99%

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Short chain fatty acid, acetate restores ovarian function in experimentally induced PCOS rat model

et al. 2022

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Background Polycystic ovarian syndrome (PCOS) is pathogenically characterized with hyperandrogenism and metabolic alterations, which often result in ovarian changes and infertility in women of reproductive age. Epigenetic changes have been linked to the development of PCOS. However, the involvement of epigenetic regulator, histone deacetylase (HDAC) in PCOS-driven ovarian dysfunction is not clear. Howbeit, the present study hypothesized that acetate, an HDAC inhibitor (HDACi) would protect against ovarian dysfunction in experimentally induced PCOS. Materials and methods Female Wistar rats weighing 120–150 g were randomly divided into four groups (n = 6). The groups received vehicle, sodium acetate (200 mg/kg), letrozole (1 mg/kg) and letrozole with acetate by oral gavage respectively. The administrations were done daily for 21 days. Results The rat model of PCOS had increased body weight and ovarian weight, 1-hr postload glucose and plasma insulin, testosterone and LH/FSH ratio as well as reduced insulin sensitivity and plasma 17-β estradiol and sex hormone binding globulin. This model of PCOS in addition showed a significant increase in plasma and ovarian triglyceride, total cholesterol, TNF-α and HDAC, and ovarian malondialdehyde as well as a significant reduction in ovarian glutathione peroxidase/reduced glutathione and NrF2 with the histology of ovarian tissues showing disrupted morphology with significant increase in the number of degenerated follicles compared with control group. These alterations were however attenuated when treated with HDACi, acetate. Conclusion Altogether, the present results suggest that acetate protects ovarian function with evidence of normal growing follicles and enhanced circulating 17-β estradiol by inhibition of HDAC.

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Section: Methodsmentioning

confidence: 99%

“…The sections (5-μm widths) were captured and then processed with an image-processing and analysis software Image-J (Version 1.52). The mean total number of degenerated follicles per section was determined after counting every ten sections as previously reported [ 28 , 31 ].…”

Section: Methodsmentioning

confidence: 99%

Short chain fatty acid, acetate restores ovarian function in experimentally induced PCOS rat model

et al. 2022

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“…In some previous studies, human PCOS patients and PCOS model rats exhibited significantly lower adiponectin values. In the current study, administration of adiponectin could significantly improve DHEA-induced PCOS in rats (40,41). Whether batokines are involved in PCOS pathophysiology is unknown, and this important question warrants further investigation.…”

Section: Discussionmentioning

confidence: 64%

Brown Adipose Tissue Activation by Cold Treatment Ameliorates Polycystic Ovary Syndrome in Rat

Yan

Zhou

et al. 2021

Front. Endocrinol.

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Polycystic ovary syndrome (PCOS) is a common endocrine disease accompanied by energetic metabolic imbalance. Because the etiology of PCOS is complex and remains unclear, there is no effective and specific treatment for PCOS. It is often accompanied by various metabolic disorders such as obesity, insulin resistances, and others. Activated brown adipose tissue (BAT) consumes excess energy via thermogenesis, which has positive effects on energy metabolism. Our previous research and that of others indicates that BAT activity is decreased in PCOS patients, and exogenous BAT transplantation can improve PCOS rodents. Notably however, it is difficult to apply this therapeutic strategy in clinical practice. Therapeutic strategies of enhancing endogenous BAT activity and restoring whole-body endocrine homeostasis may be more meaningful for PCOS treatment. In the current study, the dehydroepiandrosterone-induced PCOS rat was exposed to low temperature for 20 days. The results show that cold treatment could reverse acyclicity of the estrous cycle and reduce circulating testosterone and luteinizing hormone in PCOS rats by activating endogenous BAT. It also significantly reduced the expression of steroidogenic enzymes as well as inflammatory factors in the ovaries of PCOS rats. Histological investigations revealed that cold treatment could significantly reduce ovary cystic follicles and increase corpus luteum, indicating that ovulation was recovered to a normal level. Concordant with these results, cold treatment also improved fertility in PCOS rats. Collectively, these findings suggest that cold treatment could be a novel therapeutic strategy for PCOS.

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“…Other exclusion criteria included diabetes, hypertension, chronic renal disease, smoking, and the use of alcohol or medications. The inclusion criteria for women with normal ovulation (control group; n = 3) were a normal menstrual cycle of 21–35 d, normal ovulation confirmed by the basal body temperature test, normal ovarian form confirmed by ultrasound, normal androgen levels (<0.6 μg/L), a basic level of follicle-stimulating hormone (<10 IU/L), and a body mass index of 18.0–25.0 kg/cm 2 . Stimulation protocol for all the patients was according to the standard long protocol.…”

Section: Methodsmentioning

confidence: 99%

“…Polycystic ovary syndrome (PCOS) is a multifactorial disease associated with endocrine and metabolic disturbances in women of reproductive age and affects both fertility and pregnancy. 1 , 2 Defects in oocyte and embryo development are associated with PCOS. 3 , 4 Alteration in oocyte competence is considered to be a potential causative factor of subfertility in women with PCOS.…”

Section: Introductionmentioning

confidence: 99%

Transcriptome Profiling of Oocytes at the Germinal Vesicle Stage from Women from Mongolia with Polycystic Ovary Syndrome

Du¹,

Chen²

2021

IJGM

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Background Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders. Evidence indicates that genetic and environmental factors contribute to the pathogenesis of PCOS. The molecular basis of PCOS is not well understood. Methods Whole-genome RNA sequencing was performed on single oocyte at the germinal vesicle (GV) stage from females with normal ovulation and females with PCOS. All subjects were women from Mongolia undergoing intracytoplasmic sperm injection in vitro fertilization (ICSI-IVF) who met the Rotterdam criteria for PCOS. Women with normal ovulation who were undergoing ICSI-IVF owing to male factor infertility were recruited as control subjects. Results A total of 1313 differentially expressed genes were found by bio-informatics software in the GV oocytes of PCOS patients and compared with the control group. There were 367 upregulated and 946 downregulated genes (fold change > 2, false discovery rate < 0.01). When compared with the healthy controls, it was shown that the DEGs like VEGF, IGF, FADS1 et al were investigated as potential causes of PCOS oocytes. The DEGs were related to kinase activity, cell proliferation, gene regulation, and the signaling pathways of phosphatidylinositol 3-kinase, Hippo, and ECM-receptor pathway in patients with PCOS. In addition, the interconnected gene co-expression network was constructed by gene bionetwork analysis, indicating that ITGB5, ITGB3, and CAV2 were the core genes in regulating the module expression of DEGs in PCOS. Conclusion RNA sequencing analysis demonstrated DEGs were linked to inflammation, cardiovascular disease, and lipid metabolism in the GV oocytes of women with PCOS. We hypothesize that ITGB5, ITGB3, and CAV2 may be involved in metabolic disorders associated with the different phenotypes of PCOS.

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Low dose spironolactone-mediated androgen-adiponectin modulation alleviates endocrine-metabolic disturbances in letrozole-induced PCOS

Cited by 27 publications

References 57 publications

Short chain fatty acid, acetate restores ovarian function in experimentally induced PCOS rat model

Short chain fatty acid, acetate restores ovarian function in experimentally induced PCOS rat model

Brown Adipose Tissue Activation by Cold Treatment Ameliorates Polycystic Ovary Syndrome in Rat

Transcriptome Profiling of Oocytes at the Germinal Vesicle Stage from Women from Mongolia with Polycystic Ovary Syndrome

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