Letrozole-induced Polycystic Ovary Syndrome Research Articles

Synergistic Amelioration of Letrozole-induced Polycystic Ovary Syndrome in Rats: A Therapeutic Approach with Apple Cider Vinegar and Metformin Combination.

The present study was conducted to evaluate the combination effect of apple cider vinegar (ACV) and metformin against letrozole-induced polycystic ovary syndrome (PCOS).Female Wistar rats were administered letrozole (1mg/kg/day, p.o) for 21 days, except for the control group of animals. On the 22nd day, PCOS-induced animals were segregated into 4 groups and administered with CMC, ACV, metformin, and a combination of ACV and metformin, respectively. The treatments were continued for 15 days, and on the 36th day, all the animals were sacrificed for biochemical (blood glucose, lipid profile), hormonal (sex hormones and adiponectin), and pro-inflammatory mediator estimations in blood samples. The ovarian tissue samples were used for oxidative stress parameters and histological alterations.The PCOS control animals showed a significant alteration in the estrous cycle. The administration of letrozole resulted in the alteration of hormonal balance and elevation of body weights, glycemic state, lipid profile, pro-inflammatory mediators in serum, and oxidative stress in ovarian samples. Individual treatment groups and combination treatment groups reversed the letrozole-induced alterations in PCOS animals, and more promising results were observed with combination therapy than with individual treatment groups. Further, the therapeutic potential of the combination treatment group was also confirmed by the histological observations in the ovarian samples.The study showed that the combination of ACV and metformin significantly alleviated letrozole-induced PCOS complications in rats. This might have been achieved by mitigating the hormonal imbalance, pro-inflammatory, hyperglycemic, and hyperlipidemic states in serum, and oxidative stress in the ovary samples.

Aqueous Ethanolic Extract of Inonotus obliquus Ameliorates Polycystic Ovarian Syndrome by Modulating Oxidative Stress and Downregulating TNF-α and Interleukin-6

Polycystic ovarian syndrome (PCOS) is a complex metabolic and endocrine disorder with multifactorial etiology and complex pathogenesis. These intrinsic physiological changes cause anovulation, infertility, and miscarriage in women and exacerbate their chances of becoming hyperlipidemic and diabetic. Inonotus obliquus has been used traditionally for infertility problems. The present study aimed to investigate the therapeutic effects of aqueous ethanolic extract of Inonotus obliquus (AEIO) in female rats with letrozole-induced PCOS, along with the determination of its possible mechanism. HPLC analysis revealed the presence of gallic acid, chlorogenic acid, rutin, p-coumaric, benzoic acid, quercetin, salicylic acid, and kaempferol. Thirty female albino rats were acquired and divided into two groups (5 + 25) to induce PCOS. Letrozole (1 mg/kg) was used to induce the disease for 7 weeks (25 rats) except for the normal control (5 rats). The disease was confirmed by vaginal smear cytology, weight gain, and endocrinopathy. After disease induction, rats were divided into five groups (five rats in each group; disease control, metformin 20 mg/kg, AEIO 100, 300, and 500 mg/kg). After completion of the study, the animals were euthanized under the influence of anesthesia (chloroform). Ovaries were removed for histopathology, the liver was evaluated for oxidative stress biomarkers, and blood samples were collected for biochemical evaluation. Ovarian histopathology showed an abnormal architecture with cystic follicles and abnormal granulosa cells. Interestingly, treatment with AEIO restored normal ovarian histology with primary, growing, and developing follicles. After conducting a hormonal analysis, it was found that the induction of PCOS led to a significant increase (p < 0.001) in luteinizing hormone (LH), insulin, and testosterone levels, while the levels of follicle-stimulating hormone (FSH) decreased. However, treatment with AEIO at doses of 100–500 mg/kg restored these levels to normal. PCOS induction also resulted in oxidative stress and lipid peroxidation by significantly decreasing antioxidant enzymatic markers (SOD, CAT, and GSH) and increasing levels of lipid peroxidation enzymatic markers (MDA). AEIO restored the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), and reduced the level of malondialdehyde (MDA). In conclusion, antioxidant phytochemicals (gallic acid, chlorogenic acid, rutin, p-coumaric, benzoic acid, quercetin, salicylic acid, and kaempferol) rich extract alleviated PCOS symptomatology through modulating oxidative stress markers and eliminating ovarian low-grade inflammation by downregulating the expression of NF-κB associated TNF-α and IL-6.

Ameliorative Potentials of Vernonia amygdalina in High-fat Diet and Letrozole-induced Polycystic Ovary Syndrome in Female Wistar Rats

Ameliorative Potentials of Vernonia amygdalina in High-fat Diet and Letrozole-induced Polycystic Ovary Syndrome in Female Wistar Rats

The effect of adipose-derived mesenchymal stem cell transplantation on ovarian mitochondrial dysfunction in letrozole-induced polycystic ovary syndrome in rats: the role of PI3K-AKT signaling pathway

ObjectiveThe present study aimed to elucidate how mesenchymal stem cells (MSCs) application could efficiently attenuate pathological changes of letrozole-induced poly cystic ovary syndrome (PCOS) by modulating mitochondrial dynamic via PI3K-AKT pathway.MethodsThirty-two female rats were randomly divided into four experimental groups: Sham, PCOS, PCOS + MSCs, and PCOS + MSCs + LY294002. The Sham group received 0.5% w/v carboxymethyl cellulose (CMC); the PCOS group received letrozole (1 mg/kg, daily) in 0.5% CMC for 21 days. Animals in the PCOS + MSCs group received 1 × 106 MSCs/rat (i.p,) on the 22th day of the study. In the PCOS + MSCs + LY294002 group, rats received LY294002 (PI3K-AKT inhibitor) 40 min before MSC transplantation. Mitochondrial dynamic gene expression, mitochondrial membrane potential (MMP), citrate synthase (CS) activity, oxidative stress, inflammation, ovarian histological parameters, serum hormone levels, homeostatic model assessment for insulin resistance (HOMA-IR), insulin and glucose concentrations, p-PI3K and p-AKT protein levels were evaluated at the end of the experiment.ResultsPCOS rats showed a significant disruption of mitochondrial dynamics and histological changes, lower MMP, CS, ovary super oxide dismutase (SOD) and estrogen level. They also had a notable rise in insulin and glucose concentrations, HOMA-IR, testosterone level, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels, ovarian malondialdehyde (MDA) content as well as a notable decrease in p-PI3K and p-AKT protein levels compared to the Sham group. In the PCOS + MSCs group, the transplantation of MSCs could improve the above parameters. Administration of LY294002 (PI3K-AKT pathway inhibitor) deteriorated mitochondrial dynamic markers, oxidative stress status, inflammation markers, hormonal levels, glucose, and insulin levels and follicular development compared to the PCOS + MSCs group.ConclusionsThis study demonstrated that the protective effects of MSC transplantation in regulating mitochondrial dynamics, promoting mitochondrial biogenesis, competing with redox status and inflammation response were mainly mediated through the PI3K-AKT pathway in the PCOS model.

YKL-40 Knockdown Decreases Oxidative Stress Damage in Ovarian Granulosa Cells.

Background: Oxidative stress has been implicated in the pathogenesis of polycystic ovarian syndrome (PCOS). To develop novel antioxidant drugs, it is necessary to explore the key regulatory molecules involved in oxidative stress in PCOS. Plasma YKL-40 levels are elevated in patients with PCOS; however, its role remains unclear. Methods: The follicular fluids of 20 women with PCOS and 12 control subjects with normal ovarian function were collected, and YKL-40 in follicular fluids was measured by enzyme-linked immunosorbent assay. A letrozole-induced PCOS rat model was established and the expression level of YKL-40 in the ovaries was detected by immunohistochemistry. KGN cells were treated with H2O2 to generate an ovarian granulosa cell (OGC) model of oxidative stress. The siRNA was transfected into the cells for knockdown. The effect of YKL-40 knockdown on H2O2-treated KGN cells was evaluated by measuring proliferation, apoptosis, activities of T-SOD, GSH-Px, and CAT, levels of MDA, IL-1β, IL-6, IL-8, and TNF-α, and the PI3K/AKT/NF-κB signaling pathway. Results: YKL-40 levels were elevated in the follicular fluids of women with PCOS compared with control subjects with normal ovarian function. The expression level of YKL-40 in the ovaries of rats with PCOS is obviously higher than that in the ovaries of the control group rats. H2O2 treatment enhanced YKL-40 mRNA expression and protein secretion. YKL-40 knockdown enhanced cell proliferation and antioxidant capacity while decreasing apoptosis and inflammatory factor levels in KGN cells following H2O2 treatment. The knockdown activated the PI3K/AKT signaling pathway and suppressed NF-κB nuclear translocation from the cytoplasm. Conclusion: YKL-40 levels were elevated in the follicular fluids of women with PCOS and the ovaries of rats with PCOS. YKL-40 expression can be induced by oxidative stress, and YKL-40 knockdown can decrease oxidative stress damage in OGCs.

Ameliorative effects of Sesamum Indicum aqueous extract on Letrozole-Induced Polycystic Ovary Syndrome in Adult Female Rats and formulation of sesame syrup

Ameliorative effects of Sesamum Indicum aqueous extract on Letrozole-Induced Polycystic Ovary Syndrome in Adult Female Rats and formulation of sesame syrup

Acetate ameliorates ovarian mitochondrial dysfunction in letrozole-induced polycystic ovarian syndrome rat model by improving mitofusin-2

Androgen excess and metabolic abnormality largely contribute to the pathogenesis of polycystic ovarian syndrome (PCOS), which primarily precipitates ovarian dysfunction and infertility in reproductive-age women. Impaired mitochondrial function and epigenetic alteration have been linked to the development of PCOS. However, it is unknown whether acetate would exert a therapeutic effect on ovarian mitochondrial dysfunction in PCOS. Herein, the study hypothesized that acetate reverses ovarian mitochondrial dysfunction in experimental PCOS rat model, possibly through modulation of mitofusin-2 (MFn2). Eight-week-old female Wistar rats were randomized into four groups (n = 5). Induction of PCOS was performed by 1 mg/kg letrozole (p.o.), administered for 21 days. Thereafter, the rats were treated with acetate (200 mg/kg; p.o.) for 6 weeks. The PCOS rats demonstrated androgen excess, multiple ovarian cysts, elevated anti-mullerian hormone and leptin and decreased SHBG, adiponectin and 17-β estradiol with corresponding increase in ovarian transforming growth factor-β1. Additionally, inflammation (tumor growth factor and nuclear factor-kB), elevated caspase-6, decreased hypoxia-inducible factor-1α and elevated histone deacetylase-2 (HDAC2) were observed in the ovaries of PCOS rats, while mitochondrial abnormality with evidence of decreased adenosine triphosphate synthase and MFn2 was observed in rats with PCOS. Treatment with acetate reversed the alterations. The present results collectively suggest that acetate ameliorates ovarian mitochondrial abnormality, a beneficial effect that is accompanied by MFn2 with consequent normalization of reproductive-endocrine profile and ovarian function. Perhaps, the present data provide hope for PCOS individuals that suffer infertility.

The significant improvement in ovarian PCOS syndrome using hydralazine and alendronate aromatase inhibitor FDA-approved drugs in Wistar rat models

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. The aim of this study was to investigate the therapeutic potential of vitamin C, glutamine, mesalazine, hydralazine, and alendronate as new drug candidates for the treatment of letrozole-induced PCOS in female Wistar rats. PCOS was induced in rats by intramuscular injection of estradiol valerate (2 mg/kg body weight for 28 days). The rats then received normal saline (PCOS group), letrozole (0.5 mg/kg), vitamin C (100 mg/kg), glutamine (1000 mg/kg), mesalazine (200 mg/kg), hydralazine (30 mg/kg), and alendronate (17.5 mg/kg). Serum testosterone, LH, FSH, estradiol and progesterone levels were determined by ELISA method. H&E staining was used for histological analysis in the ovarian tissues. The groups treated with hydralazine and alendronate, show a significant decrease in testosterone, LH hormone, cystic and atretic follicles, and a significant increase in the number of single layer, multilayer, antral, graafian follicles and the volume of corpus luteum as compared to the PCOS group. Hydrolazine and alendronate appear to be effective in restoring folliculogenesis and increasing ovulation in PCOS rat. So that the natural process of ovulation and the improvement of the histology of polycystic ovaries and its shift towards healthy and active ovaries were observed. This finding supports the potential beneficial effect of hydrolazine and alendronate on improving PCOS complication.

Adiponectin improves endometrial receptivity in rats with polycystic ovary syndrome by upregulating the PPARα/HOXA10 pathway

To explore the role of the PPARα/HOXA10 signaling pathway in mediating the effect of adiponectin (APN) for improving endometrial receptivity in a rat model of polycystic ovary syndrome (PCOS). Forty female SD rat models with letrozole-induced PCOS were randomized, with 10 normal rats as the control, into 4 equal groups for treatment with APN alone, APN combined with GW6471 (a specific PPARα inhibitor) or the vehicle for 20 days, or no further treatment (PCOS model group). GW6471 treatment (daily dose of 1 mg/kg) and vehicle treatment were initiated on the 11th day following the start of APN treatment, all administered via intraperitoneal injection. The rats were observed for changes in estrous cycle, body weight, ovarian index and morphology, uterine index and morphology, serum hormone levels and lipid metabolism parameters. Endometrial expressions of PPARα and HOXA10 were detected with immunohistochemistry and Western blotting. The development of endometrial pinopodes was observed under electron microscope, and pregnancies of the rats were recorded. The rat models of PCOS exhibited obvious estrous cycle disorders with significantly prolonged estrous interval, increased body weight and ovarian index, decreased uterine index, disordered serum hormones and lipid metabolism (P < 0.05), and polycystic ovarian changes, and these changes were significantly improved by APN treatment. Endometrial expressions of PPARα and HOXA10 were significantly lowered in PCOS rats and effectively up-regulated after APN treatment, but GW6471 treatment obviously blocked the effect of APN (P < 0.05). APN showed strong protective effect against PCOS-induced impairment of endometrial pinopode development, and this effect was obviously attenuated by GW6471. APN also significantly increased the pregnancy rate and embryo number in PCOS rats, while GW6471 obviously reduced the embryo number and caused developmental retardation of the embryos. APN can improve endometrial receptivity in PCOS rats by upregulating the PARα/HOXA10 pathway.

&lt;i&gt;Artocarpus Communis&lt;/i&gt; Seed Regulates P53, IRS, HsD17β2, FTO, and CYP11a Genes in Polycystic Ovarian Syndrome Rats

Polycystic ovarian syndrome (PCOS) is a prevalent endocrine illness that affects 5-10% of reproductive women globally. It is a multifaceted hormonal disorder characterized by the involvement of numerous molecular mechanisms that contribute to its development. This study investigates the effect of &lt;em&gt;Artocarpus communis &lt;/em&gt;seed on the hormonal imbalance and P53, IRS, HsD17β2, FTO, and CYP11a genes expression in the ovaries of letrozole-induced polycystic ovarian syndrome rats. To induce PCOS in 30 female Wistar rats, letrozole was administered at a dosage of 1 mg/kg. For 12 days, &lt;em&gt;Artocarpus communis &lt;/em&gt;seed aqueous extract (100 and 250 mg/kg body weight) and Clomiphene citrate (1 mg/kg body weight), a standard medication, were given. ELISA assessed luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol levels. The levels of P53, IRS, HsD17β2, FTO, and CYP11a gene expression in the ovaries were assessed. The aqueous extract reduced LH and increased FSH levels in Letrozole-induced PCOS rats. Additionally, seed aqueous extract (250 mg/kg bw) regulated the expression of P53, type 2 17-HSD (17-HSD), fat mass and obesity-associated (FTO), 11a-hydroxylase/17,20-desmolase (CYP11a), and insulin receptor substrate (IRS) genes in the ovaries of PCOS rats. Therefore, &lt;em&gt;Artocarpus communis&lt;/em&gt; seed might have multifaceted effects on molecular pathways associated with PCOS, potentially normalizing androgen metabolism, hormonal imbalance, and ovarian function.

Oral administration of the methanolic extract of Abutilon indicum (L.) Sweet seed proves effective in reducing cystic follicles and restoring the metabolic profile of Wistar albino rats with letrozole-induced polycystic ovarian syndrome

BackgroundAbutilon indicum(L.) Sweet, a member of the Malvaceae family, is widely distributed in China and is commonly known as Dong Kui Zi. In traditional Chinese medicine, it is extensively utilized in herbal formulations to address various health conditions, and the seeds of this plant have exhibited medicinal activities relevant to polycystic ovarian syndrome (PCOS). The current investigation aimed to provide a scientific foundation for assessing the efficacy of the methanolic extract derived from A. indicum seeds (AISE) on the ovarian and metabolic functions of rats, displaying letrozole-induced PCOS. MethodologyFor this experiment, 30 Female Wistar rats were initially divided into five groups (n = 6), namely Vehicle control (VC), Low dose (LD), High dose (HD), Positive control (PC), and Negative control (NC). Four groups (LD, HD, PC, and NC) were treated with daily letrozole doses (0.5 mg/kg body weight) dissolved with 1 % Carboxymethyl cellulose (CMC) for 21 days for inducing PCOS. To assess PCOS induction, a daily examination of the estrus cycle and an Oral Glucose Tolerance Test (OGTT) were conducted on the 22ndday of the experiment. From the 22nd day, the LD and HD groups received daily oral AISE supplementation at 250 mg/kg and 500 mg/kg body weight (bw), respectively, for 28 days. Metformin (500 mg/kg) served as the PC treatment. After completion of the experimental duration, various assessments were performed to evaluate ovarian and metabolic functions. These included evaluations such as estrous cycle assessment, percentage of body weight gain, white adipose tissue (WAT) deposition, OGTT, measurement of testosterone levels, analysis of steroidogenic enzyme activity, examination of lipid profiles, assessment of oxidative stress profiles, and histopathological examinations. ResultsFollowing 21 days of letrozole treatment, the rats exhibited irregular estrous cycles and elevated OGTT. However, after 28 days of treatment with AISE and metformin, the experimental HD group demonstrated restored estrous cycle irregularity, normalized body weight gain along with WAT deposition, normalized glucose tolerance, lipid profile, antioxidative parameters, and the reinstatement of healthy ovarian architecture compared to the vehicle control group. ConclusionAdministration of AISE restores regular ovarian function in consort with homeostatic metabolic parameters in female Wister rats with PCOS and oxidative stress. These findings support the traditional use of A. indicum and further research may lead to the development of an effective natural therapy for PCOS.

Effect of Pentaclethra macrophyla Benth. Leaf on expression of P53, IRS, HsD17β2, FTO, and CYP11a genes in letrozole-induced polycystic ovarian syndrome rats

Effect of Pentaclethra macrophyla Benth. Leaf on expression of P53, IRS, HsD17β2, FTO, and CYP11a genes in letrozole-induced polycystic ovarian syndrome rats

Co-administration of probiotics and vitamin D3 ameliorates letrozole-induced polycystic ovarian syndrome in rats

Co-administration of probiotics and vitamin D3 ameliorates letrozole-induced polycystic ovarian syndrome in rats

Sinapic acid modulates oxidative stress and metabolic disturbances to attenuate ovarian fibrosis in letrozole-induced polycystic ovary syndrome SD rats.

Sinapic acid (SA) is renowned for its many pharmacological activities as a polyphenolic compound. The cause of polycystic ovary syndrome (PCOS), a commonly encountered array of metabolic and hormonal abnormalities in females, has yet to be determined. The present experiment was performed to evaluate the antifibrotic properties of SA in rats with letrozole-induced PCOS-related ovarian fibrosis. SA treatment successfully mitigated the changes induced by letrozole in body weight (BW) (p < .01) and relative ovary weight (p < .05). Histological observation revealed that SA reduced the number of atretic and cystic follicles (AFs) and (CFs) (p < .01), as well as ovarian fibrosis, in PCOS rats. Additionally, SA treatment impacted the serum levels of sex hormones in PCOS rats. Luteinizing hormone (LH) and testosterone (T) levels were decreased (p < .01, p < .05), and follicle-stimulating hormone (FSH) levels were increased (p < .05). SA administration also decreased triglyceride (TG) (p < .01) and total cholesterol (TC) levels (p < .05) and increased high-density lipoprotein cholesterol (HDL-C) levels (p < .01), thereby alleviating letrozole-induced metabolic dysfunction in PCOS rats. Furthermore, SA treatment targeted insulin resistance (IR) and increased the messenger RNA (mRNA) levels of antioxidant enzymes in the ovaries of PCOS rats. Finally, SA treatment enhanced the activity of peroxisome proliferator-activated receptor-γ (PPAR-γ), reduced the activation of transforming growth factor-β1 (TGF-β1)/Smads, and decreased collagen I, α-smooth muscle actin (α-SMA), and connective tissue growth factor (CTGF) levels in the ovaries of PCOS rats. These observations suggest that SA significantly ameliorates metabolic dysfunction and oxidative stress and ultimately reduces ovarian fibrosis in rats with letrozole-induced PCOS.

Allium ampeloprasum var. Porrum (Alliaceae) Improves Metabolic and Reproductive Disorders Associated with Polycystic Ovary Syndrome in Wistar Rats.

To provide scientific evidence of the efficacy of Allium ampeloprasum against female infertility, the effects of the aqueous extract of the said plant (AE) were evaluated in rats with letrozole-induced polycystic ovary syndrome (PCOS). AE was administered orally to PCOS rats at doses of 192, 384, and 768 mg/kg. The positive control was co-treated with clomiphene citrate (1 mg/kg) and metformin (200 mg/kg). Normal and negative controls received distilled water. The vaginal contents of rats were examined daily under a microscope before (7 days) and during treatment. Treatments were administered orally for 15 days, and then, 6 rats from each group were sacrificed for biochemical and histological analyses. The remaining rats were mated with males of proven fertility for 5 days. The daily examination of vaginal smears allowed the evaluation of fertility index. After parturition, additional fertility parameters were determined. Results showed that in PCOS rats, AE decreased body weight (p < 0.001), abdominal fat weight (p < 0.001), serum levels of LH (p < 0.001), testosterone (p < 0.001), total cholesterol (p < 0.05), and LDL cholesterol (p < 0.01). HDL cholesterol increased and atherogenic indices decreased (p < 0.001). The number of Graafian follicles and corpora lutea increased, while cystic (p < 0.001) and atretic (p < 0.05) follicles decreased. AE also decreased oxidative stress in the ovaries, restored the estrous cycle, induced uterine epithelial cell hypertrophy, and improved fertility. These effects were attributed to phenols, flavonoids, terpenoids, and anthocyanins present in AE. The overall results justify the traditional use of A. ampeloprasum against female infertility and suggest its potential use as a dietary supplement for PCOS patients.

Protective effects of vanillic acid on letrozole-induced polycystic ovarian syndrome: A comprehensive study in female wistar rats

BackgroundPolycystic ovarian syndrome (PCOS) is one of the known causes of anovulatory fertility in the world. Previous research has linked oxidative stress could contribute to PCOS, and vanillic acid has shown antioxidant potential. Hence, the present study evaluated the effect of vanillic acid on letrozole-induced polycystic ovarian syndrome in female rats. Materials and methodsPCOS was induced in Wistar female rats with letrozole (1 mg/kg, orally) in carboxymethoxycellulose (1 % w/v), administered for 21 days. After induction, the standard group received clomiphene citrate (1 mg/kg, orally) while other treatment groups were administered with vanillic acid at doses 25, 50, and 100 mg/kg, orally for 15 days, and without treatment was considered a negative control group. Different parameters studied were body weight, ovary weight, blood glucose, lipid profile, hormonal levels [luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone], markers for oxidative stress (superoxide dismutase, reduced glutathione, catalase, and malonaldehyde), and histopathology of the ovary. Statistical analysis was done for the results and p < 0.05 was considered to indicate the significance. ResultsVanillic acid-treated animals showed a concentration-dependent activity on the tested parameters. The highest tested dose (100 mg/kg) produced a more prominent effect in significantly (P < 0.001) decreasing the body weight, and ovary weight and improving the hormonal imbalance. Also, vanillic acid significantly (P < 0.01) reduced elevated blood sugar and lipid levels. Additionally, vanillic acid reduced oxidative stress significantly (P < 0.001) in the ovaries of female rats. Histopathological reports showed a reduction in cystic follicles and appearance of normal healthy follicles at different stages of development after the administration of vanillic acid. Furthermore, these effects were observed to be comparable with those recorded for standard drug, clomiphene. ConclusionThe current study data suggests that vanillic acid has protected the letrozole-induced polycystic ovarian syndrome. In the event of several side effects associated with conventional treatments used for PCOS, the findings of this study suggest the promising role of vanillic acid. More research in this direction might identify the true potency of vanillic acid in the treatment of PCOS.

Retracted: The Flavanone, Naringenin, Modifies Antioxidant and Steroidogenic Enzyme Activity in a Rat Model of Letrozole-Induced Polycystic Ovary Syndrome.

The authors requested retraction after reviewing the manuscript and determining that there were errors in the data. Reference: Yanli Hong, Yanyun Yin, Yong Tan, Ke Hong, Huifang Zhou. The Flavanone, Naringenin, Modifies Antioxidant and Steroidogenic Enzyme Activity in a Rat Model of Letrozole-Induced Polycystic Ovary Syndrome. Med Sci Monit, 2019; 25: 395-401. DOI: 10.12659/MSM.912341.

A rat study on the PTEN expression in ovarian tissue in PCOS and folliculogenesis

The objective of this investigation was to examine alterations in PTEN expression within ovarian tissue in a rat model of polycystic ovary syndrome (PCOS). The analysis also encompassed the examination of PTEN alterations in the ovarian tissue throughout the process of folliculogenesis in rats with normal ovulatory cycles. The study involved 12 adult female Sprague‒Dawley rats randomly assigned to the letrozole-induced polycystic ovary syndrome (PCOS) group as part of an animal-based research endeavour. The sections derived from the ovaries were subjected to immunohistochemical staining for PTEN. The evaluation of PTEN staining levels in ovarian tissues was conducted using electron microscopy. Follicle counts, as well as hormonal and biochemical analyses (serum luteinising hormone (LH), follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), testosterone, oestradiol levels and serum glucose, triglyceride, HDL and LDL-cholesterol levels), were conducted to provide evidence of the manifestation of polycystic ovary syndrome (PCOS) in rats. The number of primordial and Graafian follicles in the PCOS group decreased significantly, and the number of primary, secondary and antral follicles increased significantly. PTEN expression was found to be significantly higher in the PCOS group than in the control group in the primordial follicle oocyte cytoplasm, primordial follicle granulosa cells, primary follicle oocyte cytoplasm, primary follicle granulosa cells, antral follicle oocyte cytoplasm, antral follicle granulosa cells, and corpus luteum (p = 0.007, p = 0.001, p = 0.001, p = 0.001, p = 0.001, p = 0.002, and p = 0.018, respectively). In the non-PCOS group, a time-dependent comparison of the amount of oocyte cytoplasm and PTEN staining in granulosa cells of the oocytes at different stages of development was performed. While the follicles were developing from the primordial follicle to the primary and antral follicle, the amount of PTEN staining in the oocyte cytoplasm decreased, whereas the PTEN activity in the granulosa cells increased as the oocyte developed (p = 0.001 and p = 0.001, respectively). The current investigation demonstrated changes in PTEN expression in ovarian tissue throughout the course of normal folliculogenesis, as well as in instances of disrupted folliculogenesis, with a focus on rats with PCOS.

Phytochemical-Based Study of Ethanolic Extract of Saraca asoca in Letrozole-Induced Polycystic Ovarian Syndrome in Female Adult Rats.

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). Saraca asoca (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 S. asoca (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 (n = 5) and the PCOS group (n = 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 (n = 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.

Melatonin as a promising therapeutic intervention for restoring ovarian function in letrozole-induced polycystic ovary syndrome rats

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.