scholarly journals Evaluation on the characteristics of gut microbiome in polycystic ovary syndrome rats induced by dihydrotestosterone or letrozole

2021 ◽  
Author(s):  
Yan-hua Zheng ◽  
Ying Xu ◽  
Hong-xia Ma ◽  
Cheng-jie Liang ◽  
Tong Yang

Abstract Background: Etiology of polycystic ovary syndrome (PCOS) is unclear. Recent reports indicated that gut microbiota regulates metabolism and plays a major role in the development of PCOS. The present study aimed to investigate and compare the effects of dihydrotestosterone or letrozole on the gut microbiome in rats.Methods: We used dihydrotestosterone (DHT) or letrozole (LET) to induce PCOS model rats. At the end of the experiment, ovarian morphology, hormonal and metabolic status were investigated in all rats. We analyzed the gut microbiome of rats by deep sequencing the 16S rDNA V3-V4 hypervariable regions. Predictive metagenomics profiling using PICRUST revealed functional alternation of the KEGG pathways in rats.Result: Rats induced by letrozole exhibited endocrine and reproductive characteristics, such as hyperandrogenism, abnormal oestrus cycles or complete acyclic, polycystic ovaries, and obesity. DHT-induced rats were obesity, irregular oestrus cycles, polycystic ovaries, with lower level of HDL-C and lower activity of SOD than controls. The bacterial diversity (Chao1 and Ace) of DHT group was decreased compared with the control group. Furthermore, principal coordinates analysis revealed that DHT and control groups could be distinguished from each other. The DHT group exhibited increased numbers of Firmicutes, Cyanobacteria, Actinobacteria and Saccharibacteria, and decreased Bacteroidetes compared with the control group at the phylum level. Moreover, PICRUST-predicted KEGG pathways related to Carbohydrate metabolism, Amino acid metabolism, Metabolism of terpenoids and polyketides, Metabolism of other amino acids, Replication and repair, Lipid metabolism and Energy metabolism, Translation, Folding, sorting and degradation and Xenobiotics biodegradation and metabolism were significantly elevated in the DHT group. And pathways related to Metabolism of terpenoids and polyketides, Replication and repair, Xenobiotics biodegradation and metabolism, Nucleotide metabolism, Infectious diseases and Excretory system were significantly elevated in the LET group.Conclusion: The findings of the present study indicated that DHT affected the composition and diversity of gut microbial community, and leads to the gut dysbiosis. KEGG function profiles calculated by PICRUST suggested that DHT may affect metabolism of the gut microbiota more directly than letrozle.

2020 ◽  
Author(s):  
Zheng Yanhua ◽  
Ying Xu ◽  
Hongxia Ma ◽  
Chengjie Liang ◽  
Tong Yang

Abstract Background: Etiology of polycystic ovary syndrome (PCOS) is unclear. Recent reports indicated that gut microbiota regulates metabolism and plays a major role in the development of PCOS.Methods: We used dihydrotestosterone (DHT) or letrozole (LET) to induce PCOS model rat. At the end of the experiment, ovarian morphology, hormonal and metabolic status were investigated in all rats. The molecular ecology of the fecal gut microbiota was analyzed by 16S rDNA high-throughput sequencing.Result: Rats induced by letrozole exhibited endocrine and reproductive characteristics, such as hyperandrogenism, abnormal oestrus cycles or complete acyclic, polycystic ovaries, and obesity. DHT-induced rats were showed obesity, irregular oestrus cycles, polycystic ovaries, lower level of HDL-C and lower activity of SOD than controls. Our study found that DHT can reduce the microbial richness in rats. PCoA plots confirmed that DHT group was statistically significantly separated from C group and LET group. LEfSe analysis showed that the family of Bacteroidales_S24_7_group, and genus Peptococcus and Turicibacter may play vital roles in the health and function of control group. Genus of Bifidobacteriales and Vibro may play roles in the letrozole induced PCOS rats. And genus of Lachnospiraceae_NK4A136_group, Ruminococcus_1, Ruminiclostridium, Treponema_2, Anaerotruncus, Acetatifactor and Anaeroplasma may play vital roles in the intestine of DHT induced PCOS rats.Conclusion: DHT affected the composition and diversity of gut microbial community, and leads to the gut dysbiosis. Letrozole may benefit to the gut microbiome in some aspects, but it also may have a trend of inhibiting the expression of some anti-inflammatory genera in intestinal tract.


2020 ◽  
Author(s):  
Yanhua Zheng ◽  
Hongxia Ma ◽  
Ying Xu ◽  
Chengjie Liang ◽  
Tong Yang

Abstract The etiology of polycystic ovary syndrome (PCOS) is unclear. Recent reports indicated that the gut microbiome of PCOS patients and rodents has changed. In this study, we induced the nonaromatizable androgen dihydrotestosterone (DHT) or the aromatase inhibitor letrozole (LET) to induce PCOS model rat to compare the bacterial diversity distribution within and between the two groups. The molecular ecology of the fecal gut microbiota was analyzed by 16S rDNA high-throughput sequencing. Our study found that DHT can reduce the microbial richness in rats. PCoA plots confirmed that DHT group was statistically significantly separated from C group and LET group. At phylum level, DHT led to a decrease in Bacteroidetes as well as an increase in Cyanobacteria, Tenericutes, Actinobacteria, Spirochaetae and Saccharibacteria. At genus level, LEfSe analysis showed that genus of Bifidobacteriales, Vibro, Peptococcus and Turicibacter played roles in the letrozole induced PCOS rats. And Lachnospiraceae_NK4A136_group, Ruminococcus_1, Ruminiclostridium, Anaerotruncus and Anaeroplasma played vital roles in the intestine of DHT induced PCOS rats.


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):  
Zora Lazúrová ◽  
Jana Figurová ◽  
Beáta Hubková ◽  
Jana Mašlanková ◽  
Ivica Lazúrová

Abstract Objectives There is a growing evidence indicating an impact of endocrine distrupting chemicals such as bisphenol A (BPA) on human reproduction. Its higher levels in serum or urine have been documented in women with polycystic ovary syndrome (PCOS), however the relationship to ovarian steroidogenesis remains unclear. Aim of the study was to compare urinary BPA (U-BPA) concentrations among PCOS women and control group. Second aim was to assess the relationship of U-BPA to ovarian steroidogenesis in the group with PCOS. Methods Eighty six Caucasian women (age 28.5 ± 5.1 years) diagnosed with PCOS and 32 controls of age 24.9 ± 4.4 years were included in the study. Fasting blood samples were analyzed for biochemical parameters and steroid hormones. U-BPA was measured in the morning urine sample using high pressure liquid chromatography. Results PCOS women had significantly higher U-BPA as compared with control group (p=0.0001). Those with high levels of U-BPA (U-BPA ≥2.14 ug/g creatinine) demonstrated higher serum insulin (p=0.029) and HOMA IR (p=0.037), lower serum estrone (p=0.05), estradiol (p=0.0126), FSH (p=0.0056), and FAI (p=0.0088), as compared with low-BPA group (U- BPA <2.14 ug/g creatinine). In PCOS women, U-BPA positively correlated with age (p=0.0026; R2=0.17), negatively with estradiol (p=0.0001, R2=0.5), testosterone (p=0.0078, R2=0.15), free-testosterone (p=0.0094, R2=0.12) and FAI (p=0.0003, R2=0.32), respectively. Conclusions PCOS women have significantly higher U-BPA concentrations than healthy controls. U-BPA positively correlates with age and negatively with ovarian steroid hormones suggesting a possible suppressive effect of bisphenol A on ovarian steroidogenesis.


2020 ◽  
Vol 9 (6) ◽  
pp. 1831
Author(s):  
Elena Khashchenko ◽  
Elena Uvarova ◽  
Mikhail Vysokikh ◽  
Tatyana Ivanets ◽  
Lyubov Krechetova ◽  
...  

Relevance: The clinical picture of polycystic ovary syndrome (PCOS) is extremely polymorphic, especially in adolescence. At the same time, the diagnostic criteria of PCOS in adolescence are still under discussion, and the hormonal parameters, including anti-Mullerian hormone range and hyperandrogenism, are not determined. The aim of the present study was to characterize the pivotal clinical and hormonal features of PCOS in adolescents and to establish the age-specific thresholds of the most essential hormonal parameters. Design: A case-control study. Methods: The study included 130 girls with PCOS according to the complete Rotterdam criteria, aged 15 to 17 years. The control group consisted of 30 healthy girls with a regular menstrual cycle of the same age. A complete clinical and laboratory examination, hormonal assays, and ultrasound of the pelvic organs were performed. The serums anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH, prolactin, estradiol, 17α-OH progesterone (17α-OHP), androstenedione, testosterone (T), dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), leptin, and free androgen index (FAI) were analyzed. The diagnostic accuracy of AMH, FAI, LH/FSH, T, and androstenedione levels in predicting PCOS in adolescents was established using a logistic regression model and calculating area under the receiver operator characteristic (ROC) curve (AUC). Results: The serum levels of LH (9.0 (5.4–13.8) vs. 3.7 (2.5–4.7) IU/L; p < 0.0001), LH/FSH (1.6 (1.0–2.3) vs. 0.7 (0.5–1.1); p < 0.0001), 17α–OHP (4.1 (3.2–5.1) vs. 3.4 (2.7–3.8) nmol/L; p = 0.0071), cortisol (464.0 ± 147.6 vs. 284.0 ± 129.7 nmol/L; p < 0.0001), prolactin (266.0 (175.0–405.0) vs. 189.0 (142.0–269.0) mIU/L; p = 0.0141), T (1.9 (1.2–2.5) vs. 0.8 (0.7–1.1) nmol/L; p < 0.0001), androstenedione (15.8 (11.6–23.2) vs. 8.3 (6.5–10.8) ng/mL; p < 0.0001), AMH (9.5 (7.5–14.9) vs. 5.8 (3.8–6.9) ng/mL; p < 0.0001), FAI (5.5 (2.8–7.0) vs. 1.6 (1.1–2.3); p < 0.0001), SHBG (37.0 (24.7–55.5) vs. 52.9 (39.0–67.6) nmol/L; p = 0.0136), DHEAS (6.8 ± 3.2 vs. 5.1 ± 1.5 μmol/L; p = 0.0039), and leptin (38.7 ± 27.1 vs. 23.7 ± 14.0 ng/mL; p = 0.0178) were significantly altered in the PCOS patients compared to the controls. Multivariate analysis of all studied hormonal and instrumental parameters of PCOS in adolescents revealed as the most essential: AMH level > 7.20 ng/mL, FAI > 2.75, androstenedione > 11.45 ng/mL, total T > 1.15 nmol/L, LH/FSH ratio > 1.23, and the volume of each ovary > 10.70 cm3 (for each criterion sensitivity ≥ 75.0–93.0%, specificity ≥ 83.0–93.0%). The diagnostic accuracy of PCOS determination was 90.2–91.6% with the combined use of either four detected indexes, which was significantly higher than the use of each index separately. The accuracy of PCOS diagnostics reached 92% using AMH and leptin concentrations when the value of the logistic regression function [85.73 − (1.73 × AMH) − (0.12 × Leptin)] was less than 70.72. Conclusions: The results of the study estimate the threshold for AMH, FAI, androstenedione, testosterone, LH/FSH, and ovarian volume, which could be suggested for use in the PCOS diagnostics in adolescents with a high sensitivity and specificity. Moreover, the combination of either four determined indexes improved the diagnostic accuracy for the PCOS detection in adolescents.


2011 ◽  
Vol 23 (4) ◽  
pp. 520 ◽  
Author(s):  
Yun Liu ◽  
Hong Jiang ◽  
Ling-Yun He ◽  
Wu-Jian Huang ◽  
Xiao-Yu He ◽  
...  

Polycystic ovary syndrome (PCOS) may result from hypersensitivity to insulin, which is negatively regulated by uncoupling protein (UCP)-2. Because cholesterol side-chain cleavage enzyme (CYP11A1) is closely linked to PCOS, the expression of UCP-2 and CYP11A1 in ovarian tissues from PCOS patients was examined in the present study. Twelve PCOS patients with hyperandrogenaemia who underwent laparoscopic ovarian wedge resection and 12 age-matched control patients who underwent contralateral ovarian biopsy were enrolled in the study. UCP-2 expression in early stage (primordial, primary and secondary) and late stage (sinus and mature) follicles was examined using immunohistochemistry, whereas UCP-2 and CYP11A1 mRNA and protein levels in ovarian tissue were determined using quantitative reverse transcription–polymerase chain reaction and western blot analyses, respectively. UCP-2 expression increased significantly with follicular development in both control and PCOS tissue, with expression in early stage follicles from PCOS patients significantly greater than that in controls. In addition, both UCP-2 and CYP11A1mRNA and protein levels, mean fasting blood glucose concentrations and fasting serum insulin levels were significantly higher in PCOS patients compared with the control group. Finally, a significant correlation between UCP-2 and CYP11A1 expression was found in PCOS but not control patients. In conclusion, in PCOS patients, there was a correlation between UCP-2 and CYP11A1 expression, which was significantly higher than in the control group. These changes in UCP-2 and CYP11A1 expression may mediate follicle development in PCOS.


Author(s):  
Carrie Riestenberg ◽  
Anika Jagasia ◽  
Daniela Markovic ◽  
Richard P Buyalos ◽  
Ricardo Azziz

Abstract Context Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of reproductive-aged women, affecting approximately 5-20% of women of reproductive age. A previous estimate noted that the economic burden of PCOS approximates $3.7 billion annually in 2020 USD when considering only the costs of the initial diagnosis and of reproductive endocrine morbidities, not considering the costs of pregnancy-related and long-term morbidities. Objective To estimate the excess prevalence and economic burden of pregnancy-related and long-term health morbidities attributable to PCOS. Data Sources PubMed, EmBase and Cochrane Library. Study Selection Studies in which the diagnosis of PCOS was consistent with the Rotterdam, National Institutes of Health (NIH), or Androgen Excess & PCOS (AE-PCOS) Society criteria, or that used electronic medical record diagnosis codes, or diagnosis based on histopathologic sampling were eligible for inclusion. Studies that included an outcome of interest and a control group of non-PCOS patients who were matched or controlled for body mass index (BMI) were included. Data Extraction Two investigators working independently extracted data on study characteristics and outcomes. Data Synthesis Data was pooled using random-effects meta-analysis. The I 2statistic was used to assess inter-study heterogeneity. The quality of selected studies was assessed using the Newcastle-Ottawa Scale. Results The additional total healthcare-related economic burden due to pregnancy-related and long-term morbidities associated with PCOS in the United States is estimated to be $4.3 billion annually in 2020 USD. Conclusions Together with our prior analysis, the economic burden of PCOS is estimated at $8 billion annually in 2020 USD.


2020 ◽  
Vol 8 (A) ◽  
pp. 517-520
Author(s):  
Hilma Putri Lubis ◽  
Muhammad Fidel Ganis Siregar ◽  
Ichwanul Adenin ◽  
Binarwan Halim ◽  
Henry Salim Siregar ◽  
...  

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders of women in the childbearing period. However, its pathophysiology is still unclear. Certain polymorphisms of the luteinizing hormone/choriogonadotropin receptor (LHCGR) genes may lead to changes in the bioactivity of this hormone. The important functional role of LHCGR in the metabolism of androgen and ovulation, the LHCGR gene variant, may be related to the risk of PCOS. AIM: The aim of this study was to evaluate the association between LHCGR Ins18LQ gene polymorphism and PCOS. METHODS: A case–control study was performed in women with PCOS and non-PCOS from May 2019 to October 2019 in HFC IVF Center. We included 50 women with PCOS and 50 healthy controls. Polymorphism of the LHCGR (ins18LQ) gene was genotyped using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: From this study, we found that there was no significant difference in the proportion of ages between the groups (p > 0.05). There were significant differences in the characteristics of body mass index, FSH level, LH level, and LH/FSH ratio between the PCOS and control groups (p < 0.05). We also found that the proportion of heterozygote variant non-ins/ins was higher in the PCOS group compared to the control group, but there was no significant difference between the polymorphisms of the non-ins and non-nonins variants between the PCOS and control groups (p = 0.269). The frequency of ins alleles was higher in the PCOS group compared to the control group. CONCLUSION: There was no significant association between LHCGR ins18LQ gene polymorphism and PCOS.


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