Continuous Light-Induced PCOS-Like Changes in Reproduction, Metabolism, and Gut Microbiota in Sprague-Dawley Rats

Chu, Weiwei; Zhai, Junyu; Xu, Jieying; Li, Shang; Li, Weiping; Chen, Zi‐Jiang; Du, Yanzhi

doi:10.3389/fmicb.2019.03145

Cited by 55 publications

(43 citation statements)

References 50 publications

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“…At the phylum level, Bacteroidetes and Firmicutes are the dominant bacteria in the three groups. Several studies have reported that F/B ratio, which was regarded as the marker of dysbacteriosis, have positive association with enhanced inflammatory cytokines expressions ( Chu et al, 2019 ). Consistently, in the current study, this ratio was dramatically increased (12.52 folds) in the model group and reversed by the supplementation of SGD.…”

Section: Discussionmentioning

confidence: 99%

Shaoyao-Gancao Decoction Ameliorates the Inflammation State in Polycystic Ovary Syndrome Rats via Remodeling Gut Microbiota and Suppressing the TLR4/NF-κB Pathway

et al. 2021

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Background: Emerging evidence suggests that gut microbiota plays a vital role in the occurrence of multiple endocrine disorders including polycystic ovary syndrome (PCOS). Shaoyao-Gancao Decoction (SGD), a classical Chinese prescription, has been widely used in the treatment of PCOS for decades. In previous studies, we found that SGD treatment could effectively reduce ovarian inflammation in PCOS rats. However, whether the anti-inflammation effect of SGD involves the regulation of the gut microbiota remains elusive.Methods: Letrozole-induced PCOS rat models were established, and the therapeutic effects of SGD were evaluated. Specifically, body weight, serum hormone concentrations, estrus phase and ovary histopathology were assessed. Then the structure of gut microbiota was determined by 16s rRNA sequencing. Additionally, the serum levels of pro-inflammatory cytokines and LPS were measured by ELISA kits. The key gene and protein expressions of TLR4/NF-κB signaling pathway were detected by quantitative real-time PCR and western blot.Results: SGD could effectively reduce body weight, regulate estrous cycles and ameliorate hyperandrogenism in PCOS rats. In addition, SGD treatment decreased releases of pro-inflammatory cytokines, enhanced the expressions of tight junction (occludin and claudin1), and then prevented a translocation of LPS into bloodstream. SGD could significantly reduce the ratio of Firmicutes to Bacteroidetes, decrease the abundance of LPS-producing pathogens Proteobateria and enrich the abundance of Butyricicoccus, Coprococcus, Akkermansia Blautia and Bacteroides in PCOS rats. Furthermore, SGD blunted the key gene and protein expressions of TLR4/NF-κB signaling pathway both in vivo and in LPS-induced RAW264.7 cells.Conclusion: SGD administration could ameliorate the inflammatory response in PCOS rats by remodeling gut microbiome structure, protecting gut barrier, and suppressing TLR4/NF-κB signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Shaoyao-Gancao Decoction Ameliorates the Inflammation State in Polycystic Ovary Syndrome Rats via Remodeling Gut Microbiota and Suppressing the TLR4/NF-κB Pathway

et al. 2021

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“…These phenomena have also been found in rodents. Continuous light exposure could induce PCOS-like ovarian changes and glucose metabolism disorders with decreased islet beta-cell function ( 69 ). Likewise, a constant darkness treatment led to consistent results, along with arrhythmic BMAL1 expression that promoted insulin resistance via GLUT4 ( 65 ).…”

Section: Chronodisruption In the Hpg Axismentioning

confidence: 99%

“…Similarly, for PCOS, several pieces of evidence support the efficacy of light exposure modulation. In rodents, the PCOS model has been successfully built by continuous light exposure ( 69 , 106 ). The increased prevalence of PCOS in night-shift workers has been proven in a clinic survey, indicating the risk of artificial lighting ( 18 ).…”

Section: Current Progress In Circadian Medicine For the Female Reproductive Systemmentioning

confidence: 99%

Circadian Rhythms Within the Female HPG Axis: From Physiology to Etiology

Shao

Zhao

et al. 2021

Endocrinology

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Declining female fertility has become a global health concern. It results partially from an abnormal circadian clock caused by unhealthy diet and sleep habits in modern life. The circadian clock system is a hierarchical network consisting of central and peripheral clocks. It not only controls the sleep-wake and feeding-fasting cycles but also coordinates and maintains the required reproductive activities in the body. Physiologically, the reproductive processes are governed by the hypothalamic-pituitary-gonadal (HPG) axis in a time-dependent manner. The HPG axis releases hormones, generates female characteristics, and achieves fertility. Conversely, an abnormal daily rhythm caused by aberrant clock genes or abnormal environmental stimuli contributes to disorders of the female reproductive system, such as polycystic ovarian syndrome (PCOS) and premature ovarian insufficiency (POI). Therefore, breaking the "time code" of the female reproductive system is crucial. In this paper, we review the interplay between circadian clocks and the female reproductive system and present its regulatory principles, moving from normal physiology regulation to disease etiology.

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“…One such environmental factor is the disruption of the circadian cycle [ 68 ], which has for some time been suspected to be a contributing factor for PCOS pathogenesis, but has only recently been investigated experimentally [ 69 ]—prolonged exposure to continuous light was found to induce several PCOS-like changes in rats; i.e., the ovarian morphology showed abundant atretic cyst-like follicles and reduced the number of corpora lutea, demonstrating oligo/anovulation. AMH levels were significantly elevated in comparison with the control groups; the glucose metabolism, evidenced by a lower basal insulin level and decreased homeostatic model assessment, was also impaired.…”

Section: Leading Factors In Pcos Pathogenesismentioning

confidence: 99%

In Search of New Therapeutics—Molecular Aspects of the PCOS Pathophysiology: Genetics, Hormones, Metabolism and Beyond

Wawrzkiewicz-Jałowiecka

Kowalczyk

Trybek

et al. 2020

IJMS

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In a healthy female reproductive system, a subtle hormonal and metabolic dance leads to repetitive cyclic changes in the ovaries and uterus, which make an effective ovulation and potential implantation of an embryo possible. However, that is not so in the case of polycystic ovary syndrome (PCOS), in which case the central mechanism responsible for entraining hormonal and metabolic rhythms during the menstrual cycle is notably disrupted. In this review we provide a detailed description of the possible scenario of PCOS pathogenesis. We begin from the analysis of how a set of genetic disorders related to PCOS leads to particular malfunctions at a molecular level (e.g., increased enzyme activities of cytochrome P450 (CYP) type 17A1 (17α-hydroxylase), 3β-HSD type II and CYP type 11A1 (side-chain cleavage enzyme) in theca cells, or changes in the expression of aquaporins in granulosa cells) and discuss further cellular- and tissue-level consequences (e.g., anovulation, elevated levels of the advanced glycation end products in ovaries), which in turn lead to the observed subsequent systemic symptoms. Since gene-editing therapy is currently out of reach, herein special emphasis is placed on discussing what kinds of drug targets and which potentially active substances seem promising for an effective medication, acting on the primary causes of PCOS on a molecular level.

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Continuous Light-Induced PCOS-Like Changes in Reproduction, Metabolism, and Gut Microbiota in Sprague-Dawley Rats

Cited by 55 publications

References 50 publications

Shaoyao-Gancao Decoction Ameliorates the Inflammation State in Polycystic Ovary Syndrome Rats via Remodeling Gut Microbiota and Suppressing the TLR4/NF-κB Pathway

Shaoyao-Gancao Decoction Ameliorates the Inflammation State in Polycystic Ovary Syndrome Rats via Remodeling Gut Microbiota and Suppressing the TLR4/NF-κB Pathway

Circadian Rhythms Within the Female HPG Axis: From Physiology to Etiology

In Search of New Therapeutics—Molecular Aspects of the PCOS Pathophysiology: Genetics, Hormones, Metabolism and Beyond

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