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Heliyon Nov 2023Polycystic ovary syndrome (PCOS) is a common hormonal disorder that affects women of reproductive age and is characterized by multiple ovarian cysts, irregular menstrual...
Polycystic ovary syndrome (PCOS) is a common hormonal disorder that affects women of reproductive age and is characterized by multiple ovarian cysts, irregular menstrual cycles, and excessive androgen hormone production. The present study aimed to investigate the therapeutic efficacy of melatonin in alleviating PCOS-induced alterations in female Wistar rats. PCOS was induced in female albino rats by administering letrozole at a dose of 1 mg/kg for 21 days. A total of 24 rats were randomly selected and divided into four groups: group I (normal control), group II (melatonin treatment), group III (letrozole treatment), and group IV (melatonin therapy for PCOS rats). Physical parameters (body and uterus weight), hormone profile (LH and FSH), and steroidogenic enzyme activities and an oral glucose test were assessed using standard methods. Histological analysis was performed using hematoxylin and eosin staining. The results demonstrated that exogenous melatonin administration significantly improved PCOS symptoms in rats, including reduced body weight gain, changes in organ weight/body weight index, blood glucose level, percentage diestrus phase, testosterone, estradiol, progesterone, and LH/FSH ratio, as well as 3β-HSD and 17β-HSD enzyme activity. Histopathological findings revealed well-developed follicles, decreased cystic follicles, and increased antral follicles, Graafian follicles, and corpus luteum in PCOS rats treated with melatonin. These positive outcomes suggest that exogenous melatonin may hold promise as a valuable remedy for PCOS conditions in female rats. Further research is warranted to fully elucidate the underlying mechanisms and potential clinical applications of melatonin in the context of PCOS.
PubMed: 38027664
DOI: 10.1016/j.heliyon.2023.e21237 -
ACS Omega Nov 2023Polycystic ovarian syndrome (PCOS) is a complex metabolic and endocrine disorder which affects women of reproductive age. It is a condition in which ovaries produce an...
Polycystic ovarian syndrome (PCOS) is a complex metabolic and endocrine disorder which affects women of reproductive age. It is a condition in which ovaries produce an excessive amount of androgen (the male sex hormone). (Roxb.) Willd. is a plant of the Fabaceae family. This plant has been traditionally used as a uterine tonic in leucorrhea and dysmenorrhea due to its various pharmacological activities. In this study, the ethanolic extract of (EESA) was evaluated for its potential to be used for the management of PCOS. HPLC analysis revealed the presence of various phytoconstituents: kaempferol, rutin, (-)-epicatechin, salicylic acid, and gallic acid. For PCOS induction, 30 adult female rats were randomly divided into two groups: the control group ( = 5) and the PCOS group ( = 25). Letrozole (1 mg/kg/day) was administered per orally (p.o.) for a period of 7 weeks for the induction of disease. Weekly body weight measurements and daily vaginal cytology examinations were performed for disease confirmation. After disease induction, the PCOS group was further divided into five groups ( = 5), that is, disease control, metformin, and EESA (200, 400, and 600 mg/kg) groups, respectively, and given treatment doses for next 5 weeks. After the treatment period, all animals were weighed and euthanized humanly. Blood samples were collected for hormonal assays, lipid profiles, and liver function tests. For histological assessment of ovarian cysts, ovaries were dissected. Livers were preserved to evaluate EESA's antioxidant properties. Histopathology analysis revealed that EESA reduced body weight and the number of cystic follicles. Furthermore, it also lowered the elevated levels of serum testosterone, luteinizing hormone, insulin, and malonaldehyde in PCOS rats while increasing the levels of follicle-stimulating hormone, estradiol, progesterone, prolactin, and other antioxidant enzymes such as superoxide dismutase, glutathione, and catalase. It can be concluded that EESA exhibited beneficial effects in normalizing the perturbed hormonal profile and improved the ovary status by decreasing the cystic follicle and improving the ovulation status in a dose-dependent manner.
PubMed: 38024692
DOI: 10.1021/acsomega.3c05274 -
Archives of Women's Mental Health Apr 2024The goal of our study was to test whether the types of OC affect the link between anxiety and its main maintenance factors: worry and perceived stress. Women are...
Differences in anxiety, worry, and perceived stress among naturally cycling women and oral contraceptives users: a cross-sectional study investigating the role of contraceptive types.
The goal of our study was to test whether the types of OC affect the link between anxiety and its main maintenance factors: worry and perceived stress. Women are particularly at risk of being affected by excessive worrying, a core component of generalized anxiety disorder (GAD), and they are twice as likely as men to suffer from GAD. The literature suggests that gonadal hormones and types of oral contraceptives (OC) should be taken into account when exploring anxiety disorders in women, but the precise mechanism of this link remains understudied. We performed an observational cross-sectional study on a sample of 908 women, including 499 women naturally cycling (NC) and 409 taking OC (277 in the anti-androgenic group, 132 in the androgenic group). The participants filled in a battery of online questionnaires. Anxiety positively correlated with worry and perceived stress in the whole sample and in the three groups: androgenic OC, anti-androgenic OC, and NC. There was no significant difference between the groups on all the variables apart from the age of the participants. However, we found that women taking anti-androgenic OC had significantly higher levels of worry than NC women (after controlling for stress and age). The differences in OC types should be taken into account in future studies which might also lead to a better choice of OC based on women's individual needs.
Topics: Male; Humans; Female; Contraceptives, Oral; Cross-Sectional Studies; Anxiety; Anxiety Disorders; Stress, Psychological
PubMed: 38017240
DOI: 10.1007/s00737-023-01405-1 -
Life (Basel, Switzerland) Nov 2023Androgenic alopecia (AGA) is a dermatological disease with psychosocial consequences for those who experience hair loss. AGA is linked to an increase in androgen levels...
Androgenic alopecia (AGA) is a dermatological disease with psychosocial consequences for those who experience hair loss. AGA is linked to an increase in androgen levels caused by an excess of dihydrotestosterone in blood capillaries produced from testosterone by 5α-reductase type II (5αR2), which is expressed in scalp hair follicles; 5αR2 activity and dihydrotestosterone levels are elevated in balding scalps. The diverse health benefits of flavonoids have been widely reported in epidemiological studies, and research interest continues to increase. In this study, a virtual screening approach was used to identify compounds that interact with active site residues of 5αR2 by screening a library containing 241 flavonoid compounds. Here, we report two potent flavonoid compounds, eriocitrin and silymarin, that interacted strongly with 5αR2, with binding energies of -12.1 and -11.7 kcal/mol, respectively, which were more significant than those of the control, finasteride (-11.2 kcal/mol). Molecular dynamic simulations (200 ns) were used to optimize the interactions between compounds and 5αR2 and revealed that the interaction of eriocitrin and silymarin with 5αR2 was stable. The study shows that eriocitrin and silymarin provide developmental bases for novel 5αR2 inhibitors for the management of AGA.
PubMed: 38004292
DOI: 10.3390/life13112152 -
Journal of Microbiology and... May 2024Oxidative stress is a key factor in the pathogenesis of benign prostatic hyperplasia (BPH) that leads to inflammation. This study aimed to evaluate the ameliorative...
Oxidative stress is a key factor in the pathogenesis of benign prostatic hyperplasia (BPH) that leads to inflammation. This study aimed to evaluate the ameliorative effects of Bunge extract (HLT-101) on BPH through the regulation of oxidative stress and inflammation. A testosterone propionate (TP)-induced BPH rat model was orally administered HLT-101 (20, 40, or 80 mg/kg), and its effects on oxidative stress- and inflammation-related gene expression were examined. Further, HLT-101 was assessed for its effect on reactive oxygen species (ROS) levels and Nrf-2/HO-1 signaling pathways in BPH-1 cells. HLT-101 decreased testosterone-induced excessive free radical production and inflammatory factor activation. Moreover, HLT-101 treatment significantly decreased the intracellular ROS level in the TNF-α and IFN-γ treated BPH-1 cells through the activation of Nrf-2. In addition, HLT-101 treatment inhibited the NF-κB pathway and androgen receptor (AR) signaling, which is highly linked to the pathogenesis of BPH. Therefore, HLT-101 has the potential to be an effective treatment reagent for BPH because of its ability to reduce inflammation and oxidative stress via Nrf-2/HO-1 signaling.
Topics: Male; Salvia miltiorrhiza; Prostatic Hyperplasia; Oxidative Stress; Animals; NF-E2-Related Factor 2; Rats; Reactive Oxygen Species; Signal Transduction; Plant Extracts; Heme Oxygenase-1; Humans; Rats, Sprague-Dawley; Disease Models, Animal; Cell Line; NF-kappa B; Testosterone Propionate
PubMed: 37994101
DOI: 10.4014/jmb.2308.08053 -
Frontiers in Endocrinology 2023Polycystic ovary syndrome (PCOS) is a multifaceted disorder that impacts metabolism, reproduction, as well as endocrine function, characterized by excessive levels of...
BACKGROUND
Polycystic ovary syndrome (PCOS) is a multifaceted disorder that impacts metabolism, reproduction, as well as endocrine function, characterized by excessive levels of androgen and insulin resistance. The gut microbiota has been implicated in the pathogenesis of PCOS. However, the precise mechanisms through which the gut microbiota influences PCOS still require further elucidation.
METHODS
The PCOS mouse model was established through the administration of letrozole to both conventional and antibiotics-treated mice. The evaluation of glucose metabolism, sex hormone levels, and ovarian morphology was conducted. Furthermore, the fecal samples from each group of mice were subjected to 16S rRNA gene sequencing, and functional prediction of gut microbiota was proceeded using PICRUSt2 to explore potential mechanisms.
RESULTS
By using letrozole-induced PCOS mice model, we manifested that antibiotic intervention significantly reduced the serum total testosterone level and ameliorated glucose intolerance. Antibiotic treatment reduced the number of amplicon sequence variants (ASVs), as well as the Shannon and Simpson index. Meanwhile, letrozole induced a significant increase in the Shannon and Simpson index instead of ASVs. Through random forest model analysis, the results revealed significant alterations in three distinct groups of microbiota, namely Clostridia_vadinBB60_group, Enterorhabdus, and Muribaculaceae after letrozole treatment. Further correlation analysis revealed a positive association between alterations in these microbiota and both serum total testosterone levels and the area under the curve (AUC) of blood glucose in IPGTT. The administration of antibiotics led to a decrease in the absolute abundance of 5 ASVs belonging to unclassified Clostridia_vadinBB60_group, unclassified Enterorhabdus, and unclassified Muribaculaceae, which exhibited a positive correlation with the levels of total testosterone in mice serum, as well as the area under the curve of blood glucose in IPGTT. Moreover, 25 functional pathways of gut microbiome were significantly discrepant between the letrozole-treated mice with and without antibiotics.
CONCLUSION
These results suggest that disturbance of the gut microbiota may take participate in the progression of PCOS and manipulating the composition of the gut microbiota may be a therapeutic approach for managing PCOS.
Topics: Female; Humans; Mice; Animals; Polycystic Ovary Syndrome; Letrozole; Hyperandrogenism; Gastrointestinal Microbiome; Blood Glucose; RNA, Ribosomal, 16S; Testosterone; Anti-Bacterial Agents
PubMed: 37929036
DOI: 10.3389/fendo.2023.1265152 -
Frontiers in Endocrinology 2023Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age. Although promising strides have been made in the field of PCOS... (Review)
Review
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age. Although promising strides have been made in the field of PCOS over the past decades, the distinct etiologies of this syndrome are not fully elucidated. Prenatal factors, genetic variation, epigenetic mechanisms, unhealthy lifestyles, and environmental toxins all contribute to the development of this intricate and highly heterogeneous metabolic, endocrine, reproductive, and psychological disorder. Moreover, interactions between androgen excess, insulin resistance, disruption to the hypothalamic-pituitary-ovary (HPO) axis, and obesity only make for a more complex picture. In this review, we investigate and summarize the related molecular mechanisms underlying PCOS pathogenesis from the perspective of the level of signaling pathways, including PI3K/Akt, TGF-β/Smads, Wnt/β-catenin, and Hippo/YAP. Additionally, this review provides an overview of prospective therapies, such as exosome therapy, gene therapy, and drugs based on traditional Chinese medicine (TCM) and natural compounds. By targeting these aberrant pathways, these interventions primarily alleviate inflammation, insulin resistance, androgen excess, and ovarian fibrosis, which are typical symptoms of PCOS. Overall, we hope that this paper will pave the way for better understanding and management of PCOS in the future.
Topics: Pregnancy; Female; Humans; Polycystic Ovary Syndrome; Insulin Resistance; Hyperandrogenism; Androgens; Phosphatidylinositol 3-Kinases; Signal Transduction
PubMed: 37929034
DOI: 10.3389/fendo.2023.1191759 -
International Immunopharmacology Dec 2023Hyperandrogenemia and persistent chronic inflammation, two main striking features of polycystic ovary syndrome (PCOS), have been proven involved in follicular dysgenesis...
Hyperandrogenemia and persistent chronic inflammation, two main striking features of polycystic ovary syndrome (PCOS), have been proven involved in follicular dysgenesis in PCOS. However, the association between hyperandrogenism and inflammation activation in PCOS is not fully understood. Excess testosterone(T) induces inflammation and pyroptosis activation in a mouse model of PCOS, leading to ovarian dysfunction and fibrosis. Excessive endoplasmic reticulum (ER) stress is present in ovarian granulosa cells (GCs), testosterone-induced PCOS mouse and cellular models. This study found higher levels of interleukin (IL)-1β, IL-8, IL-17, and IL-18 in the follicular fluid of PCOS patients with hyperandrogenemia undergoing IVF treatment. In addition, pyroptosis in GCs was demonstrated, which was significantly elevated in PCOS patients. To clarify the association of hyperandrogenism, inflammation, and pyroptosis activation in PCOS, dehydroepiandrosterone(DHEA)-treated mouse PCOS model and T-treated KGN cell line were explored for PCOS mechanism. Markers of inflammatory activation and pyroptosis were significantly increased after DHEA treatment in mice and T treatment in KGN cells. In addition, ER stress sensor proteins were increased simultaneously. However, suppression of inflammation by genipin(GP) led to decreased pyroptosis in KGN cells but no variation in ER stress sensor proteins. In contrast, when treated with tauroursodeoxycholic acid(TUDCA) to attenuate ER stress, the markers of inflammatory factors were significantly reduced, accompanied by a reduction in pyroptosis. Our results suggest that persistent hyperandrogenemia of PCOS promotes local inflammatory activation of the ovary, and the imbalanced inflammatory microenvironment leads to pyroptosis of GCs, which is mediated by ER stress activation.
Topics: Humans; Female; Mice; Animals; Polycystic Ovary Syndrome; Hyperandrogenism; Pyroptosis; Testosterone; Inflammation; Dehydroepiandrosterone; Tumor Microenvironment
PubMed: 37918087
DOI: 10.1016/j.intimp.2023.111141 -
Human Reproduction (Oxford, England) Dec 2023Does Klinefelter syndrome (KS) lead to a distinct gene expression pattern at single-cell level in the testes that could provide insight into the reported microvascular...
STUDY QUESTION
Does Klinefelter syndrome (KS) lead to a distinct gene expression pattern at single-cell level in the testes that could provide insight into the reported microvascular dysfunction in the testes?
SUMMARY ANSWER
A distinct gene expression pattern within microvascular-associated cells of males with KS suggests excessive endothelial cell (EC) activation, disorganized vessel formation, and the presence of immature vessels with compromised integrity.
WHAT IS KNOWN ALREADY
Recent studies show that males with KS exhibit microvascular dysfunction in their testes, which affects blood flow and is associated with lower circulating levels of testosterone.
STUDY DESIGN, SIZE, DURATION
A comparative cross-sectional study of males with KS (n = 6), non-obstructive azoospermia (NOA) (n = 5), cryptozoospermia (n = 3), and controls (n = 15) was carried out.
PARTICIPANTS/MATERIALS, SETTING, METHODS
We analyzed publicly available single-cell RNA sequencing data of testicular cells from males with KS, males with NOA, males with cryptozoospermia, and controls. The integration of these datasets allowed us to analyze gene expression profiles and communication patterns among the cell types within the testis and to identify capillary ECs to investigate changes at the microvascular level.
MAIN RESULTS AND THE ROLE OF CHANCE
Rooted in changes at the single-cell level, our study demonstrates a shift in gene expression forming the foundation for altered cellular communication, microvascular remodeling, and pro-inflammatory responses within the testes of males with KS. We identified genes that were dysregulated in capillary ECs from males with KS (Padj < 0.05). Specifically, the unique microvascular gene expression in males with KS indicated enhanced capillary EC activation and increased inflammatory cross-talk, leading to impaired vessel maturation and increased EC barrier permeability.
LIMITATIONS, REASONS FOR CAUTION
Our study is constrained by an unbalanced design, with varying sample sizes and number of cells within each group. We acknowledge the restricted access to clinical information. In addition, our findings were deduced from changes in gene expression, which limits us to infer potential biological consequences arising from these alterations. Furthermore, the absence of a pre-pubertal age group limits the generalizability of our findings and warrants further investigation.
WIDER IMPLICATIONS OF THE FINDINGS
This study offers novel insights into the testicular pathophysiology in KS and underscores the potential contribution of microvascular dysfunction to the hypogonadism and infertility observed in males with KS. While this study aims to better understand the microvascular dysfunction in KS, the precise connections to testosterone deficiency and testicular atrophy remain to be fully elucidated.
STUDY FUNDING/COMPETING INTEREST(S)
A.S. was supported by the Independent Research Fund Denmark (0134-00130B). C.H.G. was supported by Novo Nordisk Foundation (NNF15OC0016474, NNF20OC0060610), 'Fonden til lægevidenskabens fremme', the Familien Hede Nielsen foundation and the Independent Research Fund Denmark (0134-00406A). E.B.J. was supported by Aarhus University and E.B.J. and C.H.G by the Independent Research Fund Denmark (2096-00165A). J.M.K. was supported by Lundbeckfonden (R307-2018-3667), Carlsberg Fonden (CF19-0687), Novo Nordisk Fonden (0073440) and Steno Diabetes Center Aarhus (SDCA). The authors declare no conflicts of interest.
TRIAL REGISTRATION NUMBER
N/A.
Topics: Male; Humans; Testis; Klinefelter Syndrome; Oligospermia; Cross-Sectional Studies; Testosterone; Microvessels
PubMed: 37910660
DOI: 10.1093/humrep/dead224 -
JCEM Case Reports Sep 2023Female androgen excess typically presents with hirsutism, acne, and frontotemporal alopecia. Although the majority of cases are due to underlying polycystic ovary...
Female androgen excess typically presents with hirsutism, acne, and frontotemporal alopecia. Although the majority of cases are due to underlying polycystic ovary syndrome, non-polycystic ovary syndrome pathology can present a diagnostic and therapeutic challenge. We present 3 cases highlighting the utility of GnRH analogues in diagnosis and treatment of ovarian hyperandrogenism. In case 1, we highlight the role of GnRH analogue testing to localize severe postmenopausal androgen excess, allowing full resolution of symptoms following resection of a benign ovarian steroid-cell tumor. Our second case demonstrates the dual utility of GnRH analogues as both a diagnostic and therapeutic agent for hyperandrogenism in a premenopausal woman with severe insulin resistance. We observed suppression of serum testosterone coupled with significant improvement in hirsutism scores. The final case describes GnRH analogue suppression as a therapeutic option for a postmenopausal woman with ovarian hyperthecosis wishing to avoid surgical intervention, with successful symptom resolution. This case series delineates the applications of GnRH analogue suppression in a variety of clinical contexts, in particular their potential role in controlling symptoms in cases of refractory androgen excess and an alternative to surgery in cases of benign ovarian hyperandrogenism.
PubMed: 37908205
DOI: 10.1210/jcemcr/luad108