Polycystic Ovary Syndrome Induction Research Articles

All-trans retinoic acid and fibroblast growth factor-2 enhance the fertility rate and embryo development in polycystic ovary syndrome mouse model.

Polycystic ovary syndrome (PCOS) causes a developmental arrest of antral follicles and disrupts oocyte maturation. Retinoic acid (RA) and Fibroblast Growth Factor-2 (FGF2) are effective in follicle growth, thus their effects on histopathology and in vitro fertility of oocytes were investigated in PCOS-induced mice. Eighty female NMRI mice were randomly divided into 8 groups including 1-Normal mice, 2-PCOS mice without any treatment, 3-Normal mice treated with RA, 4-Normal mice treated with FGF2, 5-PCOS mice treated with RA, 6- PCOS mice treated with FGF2, 7- PCOS mice treated with RA and FGF2, and 8- Normal mice treated with RA and FGF2. Following PCOS induction, the mice were treated with intraperitoneal RA and FGF2 as a treatment. Then ovarian stimulation, for preparing the oocyte and embryo microscopic examinations was performed. After oocyte morphometry, through in vitro fertilization, the embryo formation was assessed. Data was analyzed by one-way ANOVA and Tukey tests. The results showed simultaneous injection of RA and FGF2 into PCOS-induced mice increases antral follicles and corpus luteum, but decreases cystic follicles. Simultaneous injection of these two substances into healthy mice increases the pre-antral follicles and corpus luteum. Simultaneous injection of RA and FGF2 increases the number of embryos in both control and intervention groups. It can be concluded that RA and FGF2 increase the maturity of ovarian follicles, the number of two-celled embryos, and the number of grade-A embryos in mice with PCOS, which is more effective when these two substances are injected simultaneously.

Enhancement of Melanocortin-4 Receptor (MC4R) and Constancy of Kiss1 mRNAs Expression in the Hypothalamic Arcuate Nucleus in a Model of Polycystic Ovary Syndrome Rat

Background: Hypothalamic Melanocortin-4 Receptor (MC4R) and kiss1/kisspeptin systems play roles in reproductive processes. This study was conducted to evaluate changes in MC4R and kiss1 genes expression in the arcuate nucleus (ARC) of the hypothalamus and its relationship with polycystic ovary syndrome (PCOS) in rats. Materials and Methods: In the current experimental study, 24 female rats were randomly and equally allocated into nulliparous and primiparous groups and then were divided into two subgroups of PCOS and control. PCOS was induced by exposure to continuous light. Sex-related hormones were evaluated by radioimmunoassay or immunoradiometric assay. Expressions of MC4R and kiss1 gene in the ARC of the hypothalamus of the rats were evaluated by real-time PCR. Histomorphometric alterations of ovaries were compared between groups. Results: Number of tertiary follicles and their size and number of atretic follicles in the PCOS subgroups were more than those in the controls (P<0.05) whereas the number of secondary follicles and corpus luteum in the PCOS subgroups were lower than those in the controls (P<0.05). Antrum and total diameters of tertiary follicles in the PCOS subgroups were greater and granulosa layer diameter was lower than those in the controls (P<0.05). The MC4R mRNA expression in the PCOS subgroups was 6.5-fold in nulliparous and 3.5-fold in primiparous groups more than their controls’ pairs (P<0.05). However, parity did not affect the expression of MC4R gene (P>0.05).The kiss1 mRNA expression in the PCOS and control subgroups was not significantly different (P>0.05). Conclusion: Overexpression of MC4R gene after PCOS induction in the ARC of the hypothalamus may link to metabolic disorders of induced PCOS in the rats. However, alteration in the kiss1 mRNA expression after PCOS induction was not observed in the rats. [GMJ.2018;7:e1070]

The Comparative Effect of Citrullus colocynthis Hydro-Alcoholic Extract and Metformin on Morphometric Ovarian Follicles Disorders in Estradilol valerate-Iinduced Polycystic Ovary Syndrome Rats

Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects 6-10% of women in reproductive age. The medicinal values of Citrullus colocynthis extract (CCT) stems from its anti-oxidative and anti-inflammatory effects. This study evaluated the comparative effect of CCT and metformin on morphometric ovarian disorders in PCOS rats. Materials and Methods: Fifty female Wistar rats having 2-3 consecutive estrous cycles during two weeks were divided into five groups (n=10 each group). The rats in the control group only received sesame oil as estradiol valerate solvent, whereas the rats in the sham group were injected intramuscularly with 4 mg/rat estradiol valerate-induced PCOS. Following PCOS induction, the rats in the metformin group received 50 mg/kg metformin orally for three weeks. Rats in the Extract group were treated with 50 mg/kg plant extract for 21 days following the induction with PCOS. Additionally, the rats in metformin+ extract group were treated with the combination of 50 mg metformin plus plant extract for three weeks. The ovaries were removed and were fixed for tissue processing. The slices were stained by hematoxylin-eosin after clearing and hydration. Follicular count and morphometric changes were evaluated in primordial, primary, pre-antral and antral follicles. Results: The mean diameter of primordial follicle was similar in all groups, but mean diameter of primary follicle decreased in the sham group (145.50± 49.26 µm) compared to metformin (278.76± 156.64 µm), extract (311.70± 147.74 µm) and metformin+ extract groups (265.35± 88.16 µm). The diameter of pre-antral and antral follicles in the sham group were significantly larger than those in the control group, but were not significantly different in all other groups including metformin, extract, and metformin+ extract in comparison with control group (P< 0.05). Conclusion: In this study, the data has demonstrated that CCT like metformin could improve follicular morphometric disorders in PCOS rats. [GMJ.2018;7:e1045] Â

The effects of low-level laser therapy on polycystic ovarian syndrome in rats: three different dosages.

The main objective of this in vivo study was to investigate the effect of different low-level laser therapy (LLLT) doses on polycystic ovary syndrome (PCOS). In the present experimental study, a single dosage of estradiol valerate (EV) was administered to induce PCOS in female rats. After administration of the EV for induction of PCOS, rats were divided into 5 groups (n = 8/group): C group (animals that were not exposed to any form of procedure), PC group (no treatment following EV induction), L1 group (1 J/cm2 LLLT treatment following EV induction), L2 group (2 J/cm2 LLLT treatment following EV induction), L3 group (6 J/cm2 LLLT treatment following EV induction). The results indicated that no significant difference was found in the serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and progesterone (P4) between the C and L2 groups (p < 0.05). Although the serum levels of testosterone (T) were significantly higher in the C group compared with other groups (p < 0.05), the L2 group was determined to be the closest to the C group. Additionally, the LH, FSH, and T receptor level of the L2 group was closest to the C group. In conclusion, a 2 J/cm2 dosage of LLLT (L2 group) can be considered the most potentially effective treatment of PCOS in the rat. However, more studies are needed to determine the optimal dose of LLLT for the treatment of PCOS.

Chemical Characterization and Ameliorating Effect of Centratherum anthelminticum Extract against Polycystic Ovary Syndrome in Wistar Rats.

Polycystic ovary syndrome (PCOS) in females is an endocrine pathological condition of reproductive age which is usually caused by insulin resistance, hyperlipidemia, and oxidative stress. This research was aimed at evaluating the therapeutic effect of the Centratherum anthelminticum seed extract (CA) against PCOS in rodents as it is traditionally used to treat diabetes, inflammation, and gynecological problems. The CA was chemically characterized by high-performance liquid chromatography-diode array detection (HPLC-DAD). For the induction of PCOS, a high-fat diet (HFD) was given to all female Wistar rats for nine weeks except the normal control group, which was given a normal chow diet. Estradiol valerate was given to all rats except normal control. After the induction of PCOS, oral metformin (300 mg/kg) was given to the standard group, while CA was orally administered to diseased rats at 250, 500, and 750 mg/kg/day for 28 days. HPLC-DAD analysis revealed that kaempferol-3-pcoumaroylglucoside was present in the highest amount (146.8 ± 1.8 mg/g) of the extract followed by ferulic acid and malvidin-3-(6-caffeoyl)-glucoside. The in vivo results revealed a marked reduction in cholesterol and triglyceride levels in CA treatment groups. A significant rise was observed in progesterone and follicle stimulating hormone with a decrease in luteinizing hormone in the treatment groups as compared to disease control, which indicated normalization of the estrus cycle. The decrease in insulin resistance was characterized by low serum insulin levels in treatment groups. Treatment with CA also reduced inflammatory markers, such as IL-6 and NF-κB in PCOS rats. NrF2 and oxidative stress markers such as catalase, superoxide dismutase, malondialdehyde, and reduced glutathione were also improved by CA in the ovary of diseased rats. Histopathological examination showed the different developmental stages of normal follicles in CA-treated diseased rats which were indicative of a normal fertile estrous cycle. Overall, the results confirmed the efficacy of CA against PCOS in treating estradiol-HFD-induced PCOS due to its antidiabetic, anti-inflammatory, antihyperlipidemic, and antioxidant properties.

The Effects of Coenzyme Q10 on Hormonal and Histopathological Changes in Female Wistar Rats with Polycystic Ovary Syndrome

Background: Polycystic ovary syndrome (PCOS) is one the most common diseases in women in the fertility age. PCOS alters ovarian follicles and affects blood lipid profiles, liver enzymes and hormones. In this study, we tried to investigate the effects of coenzyme Q10 (CoQ10) on PCOS pathological conditions. Methods: Twenty-four female rats were randomly divided into the three groups; 1: control group, 2: PCOS group (received 1 mg/ kg letrozole daily for 21 days, PO) and 3: PCOS+CoQ10 group (received 1 mg/kg letrozole with 10 mg/kg of CoQ10 for 21 days orally). Blood lipid profiles, liver enzymes, blood glucose and testosterone levels were measured and ovarian histopathology was evaluated. Results: Histological examination showed reduced number of antral follicles in PCOS+CoQ10 group as compared with PCOS group (P&lt;0.001). PCOS increased the alanine aminotransferase (ALT) enzyme by acting on the liver (P&lt;0.01). Administration of CoQ10 during PCOS induction was able to reduce ALT levels (P&lt;0.01). PCOS increased the cholesterol (P&lt;0.05), fasting blood sugar (FBS) (P&lt;0.05), triglyceride (P&lt;0.001), low-density lipoprotein (LDL) (P&lt;0.05) and testosterone levels (P&lt;0.001) compared to the control group. However, CoQ10 treatment significantly reduced the above-mentioned parameters compared to the PCOS group. Conclusion: The results of the present study confirm that CoQ10 has a therapeutic potential for PCOS-induced lipid and hormonal changes and ovarian tissue damages. CoQ10 supplementation and its concomitant use with letrozole could inhibit the development of PCOS in rats. Testosterone reduction could be an important mechanism for CoQ10 beneficial effects.

Role of diacerein on steroidogenesis and folliculogenesis related genes in ovary of letrozole-induced PCOS mice

Polycystic ovary syndrome (PCOS), an intricate and multifaceted metabolic-endocrine disorder that typically affects 6–20% of women of reproductive age and accounts for 70–80% of all occurrences of infertility globally. In this study we focussed on the effect of diacerein (DIC) on steroidogenesis and follicle development in addition to the basic metabolic and endocrine problems which are associated with PCOS. Eighteen mature female parkes strain mice were separated into three groups at random with 6 animals in a group as follows: Group I, received water and normal diet for 66 days; group II received letrozole (LETZ) (6 mg/kg bw) for the induction of PCOS; Group III received LETZ (6 mg/kg) for 3 weeks followed by the administration of DIC (35 mg/kg) for 45 days. In our study we observed that mice with PCOS had irregular estrous cycle with increased LH/FSH, estrogen level and decline in expression of Kitl, Bmp, Cyp11a1, CYP19a1, Ar, lhr, Fshr and Esr1 as well as decreased SOD and CAT activity in ovary. Moreover, we observed increase in the expression of CYP17a1, as well as increase in serum cholesterol, triglycerides, testosterone, LH, VEGF and insulin levels. All these changes were reversed after the administration of DIC in PCOS mice. Diacerin administration reversed abnormalities in mice with PCOS by modulating the regulation of genes which are related to steroidogenesis and folliculogenesis.

Chamomile and Urtica dioica extracts improve immunological and histological alterations associated with polycystic ovarian syndrome in DHEA -induced mice

BackgroundOne of the novel mechanisms in the pathogenesis of Polycystic ovary syndrome (PCOS) is low-grade chronic inflammation. Chamomile (Matricaria recutita L.) and Nettle (Urtica dioica), with phytoestrogenic and antioxidant properties, are traditionally used to treat gynecological diseases. This study investigated the immune-modulating effects of these two plants.MethodsFollowing the induction of PCOS by subcutaneous injection (SC) of Dehydroepiandrosterone (DHEA) in BALB / C mice. Mice were treated in five groups: Sham, PCOS, PCOS + Chamomile, PCOS + Nettle, and PCOS + Chamomile and Nettle for 21 days. Ovarian morphology, blood antioxidant capacity, the abundance of Treg cells, and expression of matrix metalloproteinase-9 (MMP-9), transforming growth factor-ß (TGF-ß), cyclooxygenase-2 genes (COX-2), and tumor necrosis factor-alpha (TNF-α) were measured.ResultsFolliculogenesis, Cystic follicles, and corpus luteum improved in the treatment groups (P < 0. 05). Treg cells in the DHEA group were significantly reduced compared to the Sham group (P < 0. 01). However, this decrease was not corrected in treatment groups (P > 0. 05). Total serum antioxidant capacity was significantly increased in the treatment group of Nettle and Chamomile + Nettle (P < 0. 05). The expression of MMP9 and TGFβ genes in the PCOS group was significantly higher than the Sham group (P < 0. 05), which the expression of MMP9 was corrected by treatment with Chamomile + Nettle extract (P < 0. 05).ConclusionChamomile and Nettle extract may be an effective supplement in improving the histological and immunological changes of PCOS. However, more research is needed to confirm its effectiveness in humans.

The Effects of Clove Oil on The Biochemical and Histological Parameters, and Autophagy Markers in Polycystic Ovary Syndrome-Model Rats.

This study aimed to determine whether syzygium aromaticum (clove) could help polycystic ovary syndrome (PCOS) rats. In this experimental study, forty adult female Wistar rats (weighing 250 ± 10 g) were divided randomly into five groups; G1: control, G2: PCOS group, G3: PCOS+clove (30 mg/kg/ orally/daily) group, G4: PCOS+clove (60 mg/kg/orally/daily) group, and G5: PCOS+gonadectomy group. The PCOS was induced by a single dose injection of estradiol valerate (16 mg/kg/IM). Following PCOS induction, the rats were treated for 14 days. Histological parameters, follicle apoptosis, mRNA expression of autophagy markers (Lc3, Beclin1), oxidative stress markers, insulin and blood glucose levels, as well as serum levels of aromatase and testosterone were evaluated in these rats. Finally, the ratio of serum luteinizing hormone (LH) to follicle-stimulating hormone (FSH) levels was also calculated. The autophagy markers (Lc3, Beclin1), histological parameters, oxidative stress, insulin, and hormone levels changed significantly in the PCOS rats (G2). In G3 and G5 groups, it was observed that the levels of LH/FSH and testosterone decreased significantly in comparison to the PCOS group, and inhibition of autophagy was also observed in these groups. Treatment with cloves in the G3 group significantly improved oxidative stress, histological parameters, and insulin levels. These findings demonstrated that oxidative stress, apoptosis, and excessive autophagy could be improved by treatment with low doses of clove and gonadectomy. Cloves may help to improve these parameters by regulating and inhibiting excessive autophagy. However, discovering the direct role of this extract in regulating the parameters such as oxidative stress, insulin, and androgens requires further investigation. In the present study, P<0.05 was considered statistically significant.

Milicia excelsa (Moraceae) reversed the effects of letrozole-induced aromatase inhibition in rats with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is an endocrinopathy affecting 5-20% of women of childbearing age.There is no single drug for the treatment of PCOS and current therapies have significant side effects. This study evaluated the ability of Milica excelsa to improve PCOS symptoms in rats. Induction of PCOS was achieved using letrozole (areversible aromatase inhibitor; 1mg/kg; given orally for21days). From day 22, PCOS rats received the aqueous extract of M.excelsa roots (14 and 140mg/kg). Clomiphene citrate (1mg/kg) was administered to the positive control. The negative and the normal controls received the vehicle (5%DMSO). Treatments were given orally for 7 or 14days. Vaginal smears were scrutinized daily during the experiment. Body weight was measured hebdomadal. Animals were sacrificed after the two treatment periods for biochemical and histological analyses. Aromatase inhibition caused hyperandrogenism (p<0.001), overweight (p<0.001) and fat accumulation (p<0.001). It also blocked the estrous cycle at the diestrus phase and altered ovarian dynamics as evidenced by the accumulation of cystic (p<0.001) and atretic (p<0.001) follicles. In contrast, M.excelsa induced weight loss (p<0.001), reduction in fat weight (p<0001), and lower serum androgen and LH levels (p<0.001). It also restored the estrous cycle andimproved ovarian dynamics by increasing the amount of Graafian follicles (p<0.001) and corpora lutea (p<0.001), and decreasing that of cystic and atretic follicles (p<0.001). Milica excelsa corrected hyperandrogenism and overweight in PCOS animals, and reduced cyst formation and follicle atresia in their ovaries.

Quercetin modulates ovarian autophagy–related molecules and stereological parameters in a rat model of PCOS

Objective: To examine the effect of quercetin on stereological parameters and autophagy-related genes in ovaries of polycystic ovary syndrome (PCOS) rats.Methods: Fifty female Sprague-Dawley rats were randomly divided into five groups: the control group, the ethanol group, the quercetin group (15 mg/kg/day), the PCOS group, as well as the PCOS + quercetin group. After the induction of PCOS, quercetin was administered orally for 30 days. Histological, stereological and real-time PCR analyses were carried out to evaluate the effect of quercetin on PCOS rats.Results: Stereological analysis revealed that quercetin significantly increased the number of ovarian follicles and the volume of corpus luteum and induced a significant decrease in atretic follicles in comparison to the PCOS group. In addition, quercetin markedly increased mTOR gene expression while decreasing Beclin-1 and LC3 gene expression.Conclusions: Quercetin strongly modulates the expression of ovarian autophagy-related genes and stereological parameters in PCOS rats. Therefore, it can be considered as an ameliorative component for ovarian follicular impairments.

Protective effect of astaxanthin and metformin in the liver of rats in which the polycystic ovary syndrome model was formed by giving letrozole.

In this study, the effects of astaxanthin on liver tissue in rats with polycystic ovary syndrome (PCOS) were evaluated. Fifty-four Spraque-Dawley rats were divided into 9 groups: Groups: Control, PCOS, PCOS+Metformin (Met), PCOS+ Astaxanthin (ASX)10, PCOS+ASX20, PCOS+ASX40, PCOS+Met+ASX10, PCOS+Met+ASX20, and PCOS+Met+ASX40. PCOS was induced in female rats by oral administration of letrozole (1 mg/kg) for 21 days. Rats were treated with ASX (10 mg/kg), ASX (20 mg/kg), ASX (40 mg/kg), and metformin (20 mg/kg) for 7 days after PCOS induction. At the end of the experiment, malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured in the liver tissue. The liver was stained with hematoxylin/eosin for histological examination. Additionally, NF-kB and caspase 3 were analyzed immunohistochemically. A remarkable abnormality was observed in the biochemical and histological parameters in the liver tissue of the PCOS model rats. Astaxanthin dose-dependently normalized the MDA level. Additionally, astaxanthin showed a protective effect by increasing the SOD level and increasing its antioxidant activities. We observed that administration of astaxanthin in addition to metformin applied in the standard was more effective. Caspase 3 and NF-kB immune positivity was lower in the groups given astaxanthin compared with PCOS. Histologically, it was observed that astaxanthin improved the deteriorated liver morphology in the letrozole-induced PCOS group. According to our results, it was observed that astaxanthin had antioxidant, anti-inflammatory and anti-apoptotic effects on PCOS in the treatment groups. Therefore, it was concluded that astaxanthin may have a protective effect against PCOS side effects.

A novel herbal combination ameliorates ovarian dysfunction and regulates altered biochemical parameters in rats with letrozole-induced polycystic ovary syndrome

Objective: To investigate the potential activity of novel herbal combination and novel herbal formulation (syrup) in female Sprague Dawley rats with letrozole-induced polycystic ovary syndrome (PCOS).Methods: Forty-two rats were randomly divided into seven groups with six rats in each group. Group 1 received 0.5% carboxy methylcellulose orally for 37 days and served as the normal control group. Group 2 was orally administered with letrozole of 1 mg/kg for 21 days and served as the PCOS induction group without treatment. Group 3 to 7 were administered with letrozole of 1 mg/kg for 21 days orally to induce PCOS, and then respectively received clomiphene citrate at 1 mg/kg, 100 and 200 mg/kg of novel herbal combination, 200 mg/kg of novel herbal formulation (syrup), and 400 mg/kg of marketed formulation of Pushyanuga churna, once daily for 15 days. Effects of the novel herbal combination and its syrup formulation were evaluated on the hormonal profile, the levels of antioxidants, the lipid profile and on the ovarian morphology, using letrozole-induced PCOS model in rats.Results: Letrozole caused alterations in hormonal levels and lipid levels similar to PCOS and ovarian histology showed presence of ovarian cysts confirming the induction of PCOS in rats. On treatment with the novel herbal combination and its syrup formulation in PCOS-induced rats, the altered hormonal and lipid profiles showed significant recovery to normal levels. Ovarian histology confirmed the restoration of folliculogenesis in the PCOS-induced rats. The treatment with the syrup formulation of novel herbal combination was found to be more effective than novel herbal combination and showed better recovery in various parameters evaluated. The results of the study, however, suggested that treatment with novel herbal combination and its syrup formulation provided minimal protection against oxidative stress caused due to the induction of PCOS.Conclusions: The integrated approach for management of PCOS is to counterbalance the limitations associated with modern therapy. Both the novel herbal combination and the syrup formulation of novel herbal combination show efficacy in the management of PCOS in rats and restore folliculogenesis in the ovary. The syrup formulation of novel herbal combination is most effective in the management of PCOS and shows potential to be developed as an adjuvant therapeutic agent.

Beneficial effects of Teucrium polium hydroalcoholic extract on letrozole-induced polycystic ovary syndrome (PCOS) in rat model.

Polycystic ovary syndrome (PCOS) is an endocrine disorder that disrupts the menstrual cycle and causes infertility. Considering the increasing use of medicinal plants, the present study aimed to evaluate the effects of Teucrium polium L. on letrozole-induced PCOS in female rats. Six groups of rats (n=7 each) were evaluated. The control group received 1% carboxy methyl cellulose as vehicle, while the five other groups received letrozole 1 mg/kg orally for 21 days. After PCOS induction, the rats were orally administered T. polium extract (50, 100, 200 mg/kg) or metformin (200 mg/kg) for 28 days. Subsequently, body and ovarian weights and serum levels of follicle stimulating hormone, luteinizing hormone (LH), estradiol, progesterone, and testosterone were measured. Finally, the ovarian tissues were isolated for histological examination. There were no significant changes in weekly body weight in any group. After 21 days of letrozole administration, PCOS induction was confirmed by estrous cycle irregularities and increased LH and testosterone levels. After treatment with the hydroalcoholic extract of T. polium, testosterone and LH levels were significantly reduced in all groups (P<0.05). Histological studies of ovaries in the metformin and T. polium groups exhibited normal follicular development with fewer and smaller cystic follicles than those in the PCOS group. The hydroalcoholic extract of T. polium improves serum levels of sex hormones, restores ovarian morphology in PCOS-induced rats, and is a good candidate for further clinical trials.

Therapeutic effect of Ferula assa-foetida oleo-gum resin in rats with letrozole-induced polycystic ovary syndrome.

Asafoetida is a gum derived from Ferula assa-foetida, which is used in traditional Iranian medicine to treat some reproductive system disorders. The effects of asafoetida on ovarian tissue, expression of certain genes associated with polycystic ovary syndrome (PCOS), and levels of liver, kidney, and blood cell factors after treatment in a rat model were investigated. Thirty rats were divided into five groups: normal, polycystic, and treatment with three doses of asafoetida (12.5, 25, and 50 mg/kg for 3 weeks after PCOS induction). PCOS was induced by letrozole at a dose of 1 mg/kg administered orally for 3 weeks. Blood samples were taken, and the ovaries were removed and prepared for histomorphometric examination. Liver and kidney parameters were measured. The mRNA expression levels of luteinizing hormone receptor, CYP11A1, adenosine monophosphate-activated protein kinase, adiponectin, and adiponectin receptors 1 and 2 were also measured by real-time polymerase chain reaction. The levels of liver, kidney, and blood parameters did not significantly differ between the treatment groups and the control group. At doses of 25 and 50 mg/kg, ovarian histopathology, especially the thicknesses of the theca and granulosa layers, was significantly improved relative to the PCOS group. The expression of target genes also improved in the 25 and 50 mg/kg treatment groups. Asafoetida can be used to treat PCOS as a complementary approach to conventional therapies. Asafoetida appears to act by regulating and activating metabolic and ovarian cycle enzymes.

Efficacy of Flavonoids on Animal Models of Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.

Polycystic ovary syndrome (PCOS) is one of the most common gynecological endocrinopathies. Evidence suggest that flavonoids have beneficial effects on endocrine and metabolic diseases, including PCOS. However, high-quality clinical trials are lacking. We aimed to conduct a systematic review and meta-analysis of experimental studies to determine the flavonoids’ effects in animal models of PCOS. Three electronic databases including PubMed, Scopus, and Web of Science were systematically searched from their inception to March 2022. The Systematic Review Center for Laboratory Animal Experimentation’s risk of bias tool was used to assess methodological quality. The standardized mean difference was calculated with 95% confidence intervals as the overall effects. R was used for all statistical analyses. This study was registered in PROSPERO (registration number: CRD42022328355). A total of eighteen studies, including 300 animals, met the inclusion criteria. Our analyses demonstrated that, compared to control groups, flavonoid groups showed a significantly lower count of atretic follicles and cystic follicles and the count of corpus luteum was higher. A significant reduction in the luteinizing hormone (LH), LH/follicle-stimulating hormone (FSH), and free testosterone were observed in intervention groups. Nevertheless, there was no significant difference in the effects of flavonoids on the level of FSH, estradiol, and progesterone. Subgroup analyses indicated that the type of flavonoid, dose, duration of administration, and PCOS induction drug were relevant factors that influenced the effects of intervention. Current evidence supports the positive properties of flavonoids on ovarian histomorphology and hormonal status in animal models of PCOS. These data call for more randomized controlled trials and further experimental studies investigating the mechanism in more depth.

Fenofibrate ameliorates letrozole-induced polycystic ovary in rats via modulation of PPARα and TNFα/CD95 pathway.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine health problem during the childbearing period that seriously affects fertility in females. Fenofibrate, a peroxisome proliferator-activated receptor-alpha (PPARα) agonist, showed beneficial effects in models of endocrine disturbances. Thus, we evaluated the potential therapeutic effect of fenofibrate in experimental PCOS. Rats received oral fenofibrate (300 mg/kg/day) for three weeks following a three-week PCOS induction regimen using oral letrozole (1 mg/kg/day). We determined the changes in body weight, levels of serum testosterone, insulin, anti-Müllerian hormone (AMH), ovarian malondialdehyde (MDA), superoxide dismutase (SOD), and tissue tumor necrosis factor-alpha (TNFα) and CD95 protein expressions. The tissue expression of interleukin-10 (IL10) and PPARα genes was determined. Letrozole-treated rats showed successful induction of PCOS, confirmed by histopathology and significantly increased body weight, testosterone, insulin, AMH, and MDA, and decreased SOD. Ovaries of untreated PCOS rats showed increased TNFα and CD95 and decreased PPARα and IL10 expression. Administration of fenofibrate ameliorated the letrozole-induced PCOS changes. Fenofibrate-mediated amelioration of PCOS in rats is attributed partly to its antioxidant, anti-inflammatory, and anti-apoptotic properties and activation of PPARα.

Effect of Silibinin on Dyslipidemia and Glycemic Alteration Associated with Polycystic Ovarian Syndrome: An Experimental Study on Rats.

PurposeFemales with polycystic ovary syndrome (PCOS) are found to have hormonal and metabolic alterations. This study investigated the efficacy of the flavonolignan silibinin in restoring the metabolic alterations associated with letrozole-induced PCOS in rats.MethodsThe study allocated 42 albino rats into two groups. The first group was a normal control group (n=12) in which only the vehicle was given. The second group, the PCOS group (n=30), received letrozole (1 mg/kg/day) orally for 21 days. On day 21, six animals from the first group and six animals from the second group were sacrificed to confirm the development of PCOS, and the rest of the animals (n=24) in the second group were distributed equally into four groups: the PCOS group received vehicle, the metformin (MET) group received 300 mg/kg metformin orally, and the low-dose silibinin (LD-100) and high-dose silibinin (HD-200) groups received 100 and 200 mg/kg silibinin intraperitoneally, respectively. Blockade of the estrus cycle in the diestrus phase, hyperglycemia, and body weight elevation were related to a positive PCOS induction. An oral glucose tolerance test (OGTT) was also carried out for all animals on day 21 and on the last day of the experiment (day 40) to investigate the effect of silibinin on insulin resistance. The rats’ lipid profile, insulin level, estrus cycle patterns, body weight, and weights of the ovaries and uterus were also measured on day 40.ResultsA 19-day silibinin treatment led to the restoration of regular estrus cyclicity, reduced the glucose spike in OGTT analysis, and alleviated insulin resistance in PCOS rats. There was a statistically non-significant decrement in insulin level and lipid profile in the treatment groups.ConclusionSilibinin flavonolignan ameliorated some metabolic and reproductive alterations associated with PCOS. This could be related to the decreased insulin resistance, and antiandrogenic and phytoestrogenic activity of silibinin. Further study with longer term therapy is recommended to clarify more potential effects of silibinin and its mechanism of action in PCOS.

The Efficacy of Chinese Herbal Medicine in Animal Models of Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.

Objective This study aimed to evaluate the efficacy of Chinese herbal medicine (CHM) on ovarian mass, weight, sex hormone disorders, and insulin resistance in animal models of polycystic ovary syndrome (PCOS). Methods This systematic review and meta-analysis was conducted through a comprehensive search in three databases to find studies testing CHM in animal models of PCOS. Two researchers independently reviewed the retrieval, extraction, and quality assessment of the dataset. The pooled effects were calculated using random-effect models; heterogeneity was explored through subgroup analysis; and stability was assessed through sensitivity analysis. In addition, publication bias was assessed using the Egger's bias test. Results Fifteen studies with twelve mice and 463 rats published from 2016 to 2021 met the inclusion criteria. The results of primary outcomes revealed that CHM therapy was significantly different with control animals in ovarian mass and testosterone (SMD, −1.01 (95% CI, −1.58, −1.45); SMD, −1.62 (95% CI, −2.07, −1.16), respectively). The secondary outcomes as well showed an overall positive effect of CHM compared with control animals in weight (SMD, −1.02 (95% CI, −1.39, −0.65)), follicle-stimulating hormone (FSH) (SMD, 0.58 (95% CI, 0.19, 0.97)), luteinizing hormone (LH) (SMD, −0.94 [95% CI, −1.25, −0.64)), homeostasis model assessment-insulin resistance (HOMA-IR) (SMD, −1.24 (95% CI, −1.57, −0.92)). Subgroup analyses indicated that PCOS induction drug, formula composition, random allocation, and assessment of model establishment were relevant factors that influenced the effects of interventions. The stability of the meta-analysis was showed robust through sensitivity analysis. The publication bias was substantial. Conclusions Administration with CHM revealed a statistically positive effect on ovarian mass, weight, sex hormone disorders, and insulin resistance. Moreover, these data call for further high-quality studies investigating the underlying mechanism in more depth.

Interplay between polycystic ovary syndrome and hypothyroidism on serum testosterone, oxidative stress and StAR gene expression in female rats.

IntroductionEndocrine disorders such as polycystic ovary syndrome (PCOS) and hypothyroidism can cause infertility. There are evidence that they happen jointly in some circumstances. It still remains unknown, how these two illnesses interact and influence the body.MethodsAccordingly, a five‐group was designed, first is the control group, followed by the PCOS group. Estradiol valerate (EV) induced PCOS, the second group had only PCOS and the third, fourth and fifth groups were given varied dosages of propylthiouracil (PTU) to cause hypothyroidism after induction of PCOS. Steroidogenic acute regulatory protein (StAR) expression was measured in the ovaries, and serum was obtained to determine testosterone levels, as well as superoxide dismutase (SOD) as an antioxidant and malondialdehyde (MDA) as an oxidant.ResultsBased on radioimmunoassay data, testosterone levels were significantly higher in the PCOS group than the control group, and significantly lower (p ˂ .05) in PTU groups comparing with the PCOS group. According to the quantitative real‐time polymerase chain reaction (qRT‐PCR) data, the same results were obtained for the StAR gene as well. The data also indicated a positive correlation between these two. Although both oxidant and antioxidant level increased in PCOS group compared than control group, after hypothyroidism, oxidant level increased significantly (p ˂ .05), meanwhile antioxidant level decreased significantly (p ˂ .05).ConclusionsThe results of this study illustrate that the presence of both PCOS and hypothyroidism alters the situation more than just PCOS. They also indicate that this situation is associated with imbalanced oxidative/antioxidative status.