Molecular regulation of polycystic ovary syndrome: altered gene expression levels in mouse models pretreatment and post-treatment

Summary Polycystic ovary syndrome (PCOS) is a complex disorder and genetic factors are believed to play a role. The main aim was to investigate expression levels of genes involved in PI3K/AKT signalling pathway pretreatment and post-treatment. Mouse models of PCOS were generated. Group one included control mice with no polycystic ovaries (n = 4), Group 2 included a PCOS mouse model (n = 8), Group 3 included PCOS mice treated with clomiphene citrate (n = 7) and Group 4 included PCOS mice treated with clomiphene citrate, metformin and pioglitazone (n = 8). Histochemical analyses were performed. Total RNA was extracted and cDNA was synthesized. Irs, Akt1 and Akt2, mTor and Pdpk1 gene expression levels were evaluated by RT-PCR amplification. In Group 1, cortex and medulla were evaluated as normal; in Group 2, ovarian cortex was composed of immature oocytes and cystic follicles with atretic follicles. In Groups 3 and 4, follicles were in the process of normal follicle differentiation. The expression levels of Akt1 and Pi3k were significantly different (P < 0.0001) between Groups 1 and 2. The significant differences in expression levels of Pi3k and Akt1 were also observed between the Group 1 and both Groups 3 and 4 (P < 0.0001). Furthermore, significant variations of the expression levels of mTor between Groups 1 and 4 were observed. The extrapolation of results of this study may imply that follicular development may be regulated by molecular pathways involving Pi3k, Akt1 and mTor expression. Therefore, genes in the PI3K/AKT pathway may have a direct regulatory role in the development of PCOS.

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Comparision of Rosiglitazone Maleat Only Use with Combination with Clomiphene Citrate in Infertile Cases with Clomiphen Resistant Polycystic Ovary Syndrome Cases

İstanbul Kanuni Sultan Süleyman Tıp Dergisi ◽

10.5222/iksstd.2021.87609 ◽

2021 ◽

Author(s):

Sevinç Ünal ◽

Memet Şimşek

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Statistical Significance ◽

Clomiphene Citrate ◽

Pregnancy Rates ◽

Induction Agent ◽

Ovary Syndrome ◽

Insulin Sensitizer ◽

Group 2 ◽

Group 1

INTRODUCTION: Most of the obese PCOS patients are resistant to clomiphene citrate standard doses. In these cases metabolic syndromes are treated by using insulin sensitizing drugs so that ovulation can be achieved.In this study rosiglitazine maleat was used in order to induce ovulation in obese clomiphene resistant PCOS patients. METHODS: 30 women(18-40 year old) with clomiphene resistant polycystic ovary syndrome that were obese (BMI>25 kg/m2) and hyperinsulinemic were seperated in two groups. In the first group (n=15) oral antidiabetic Rosiglitazone maleate( 4mg bid) which belongs to thiazolidinediones were used.In the second group(n=15) in addition to clomiphen citrate(50 bid)and Rosiglitazone maleate(4 mg bid) were used, ovulation and pregnancy rates were compared. In both groups ovulation and pregnancy were recorded, in the second group ovulation and pregnancy rates were higher than the first group but these rates were not significant. RESULTS: In group 1, ovulation was achieved in 5 patients (%33) and pregnancy was achieved in 1 patient (%7). In group 2, ovulation was achieved in 9 patients (%60) and pregnancy was achieved in 3 patients (%20).There was no statistical significance between two groups. DISCUSSION AND CONCLUSION: In our study in obese and hyperinsulinemic patients rosiglitazone maleat can induce ovulation and in addition to clomiphene citrate also ovulation can be achieved although it is statistical insignificant. As a result Rosiglitazone maleate can be used alternatively as an insulin sensitizer and ovulation induction agent.

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Impact of Luteal phase clomiphene citrate on endometrial thickness and clinical pregnancy rates in women with polycystic ovary syndrome

Obstetrics & Gynecology International Journal ◽

10.15406/ogij.2020.11.00503 ◽

2020 ◽

Vol 11 (3) ◽

pp. 158-161

Author(s):

Elsayed Elshamy ◽

Ayman Soliman

Keyword(s):

Polycystic Ovary Syndrome ◽

Luteal Phase ◽

Polycystic Ovary ◽

Endometrial Thickness ◽

Clomiphene Citrate ◽

Clinical Pregnancy ◽

Ovary Syndrome ◽

Clinical Pregnancy Rates ◽

Group 2 ◽

Group 1

Objective: To compare between luteal phase clomiphene citrate and second cycle day clomiphene citrate on the thickness of the endometrium and clinical pregnancy rates in women with polycystic ovary syndrome. Methods: a prospective observational study conducted on 196 women with Polycystic ovary syndrome divided into two groups: Group 1 (98 patients) received 100mg of clomiphene citrate daily for 5 days starting on second cycle day and Group 2 (98 patients) received 100mg of clomiphene citrate daily starting in the luteal phase before onset of withdrawal bleeding for 5 days. Treatment and follow up applied for three cycles. Outcome measures were collected and analyzed and women who got pregnant were followed until 12 weeks of pregnancy. Results: no significant differences between the two groups regarding pre-ovulatory endometrial thickness (8.3mm in group 1vs 8.8mm in group 2), number of mature follicles (1.62 in group 1vs 1.57 in group 2) and mid-luteal serum progesterone levels(14.63ng/ml in group 1vs 14.9ng/ml in group 2). 34 women (35%) got pregnant in group 1 and 37 women (38%) in-group 2 and three patients had miscarriage in each group without any statistical significance. Conclusion: the present study does not support luteal clomiphene citrate over second cycle day clomiphene citrate to induce ovulation in infertile women with polycystic ovary syndrome.

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The Effectiveness of Herbal Mixture Supplements with and without Clomiphene Citrate in Comparison to Clomiphene Citrate on Serum Antioxidants and Glycemic Biomarkers in Women with Polycystic Ovary Syndrome Willing to Be Pregnant: A Randomized Clinical Trial

Biomolecules ◽

10.3390/biom9060215 ◽

2019 ◽

Vol 9 (6) ◽

pp. 215 ◽

Cited By ~ 2

Author(s):

Nava Ainehchi ◽

Arash Khaki ◽

Azizeh Farshbaf-Khalili ◽

Mohamad Hammadeh ◽

Elaheh Ouladsahebmadarek

Keyword(s):

Clinical Trial ◽

Polycystic Ovary Syndrome ◽

Randomized Clinical Trial ◽

Polycystic Ovary ◽

Clomiphene Citrate ◽

Ovary Syndrome ◽

Herbal Mixture ◽

Group 3 ◽

Group 2 ◽

Group 1

This paper aimed to evaluate the effect of herbal mixture (Mentha spicata, Zingiber officinale, Cinnamomum zeylanicum, and Citrus sinensis) only and along with clomiphene citrate (CC) compared to CC on serum antioxidants, glycemic status, menstrual regulation, and rate of pregnancy. This single-blind randomized clinical trial was carried out on 60 infertile participants with polycystic ovary syndrome (PCOS) willing to be pregnant. They were randomly allocated into group 1 (n = 20) who received routine dose of CC pills (50–150 mg) for three menstrual cycles from the fifth day of menstruation for five days; group 2 (n = 20) who consumed herbal mixture daily (700 mg); and group 3 (n = 20) who used up herbal mixture along with CC for 3 months. Catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), malondialdehyde (MDA), fasting blood sugar (FBS), insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) were measured in their blood samples. No statistically significant differences were observed between the three groups in terms of socio-demographic characteristics. After intervention, however, the levels of CAT in group 2 (adjusted mean difference (aMD): = 9.0; confidence interval (CI) 95% = 1.1–16.9) and group 3 (aMD = 12.2; CI 95% = 4.5–19.9), GPx in group 2 (aMD = 986.1; CI 95% = 141.1–1831.1) and group 3 (aMD = 1781.2; CI 95% = 960.7–2601.8), and SOD in group 2 (aMD = 55.1; CI 95% = 26.0–84.2) increased. While FBS in group 3 (aMD = −8.7; CI 95% = −14.7 to −2.7), insulin in group 2 (aMD = −5.6; CI 95% = −10.8 to −0.4), and HOMA-IR in group 2 (aMD = −1.3; CI 95% = −2.4 to −0.2) significantly decreased compared to the group 1. To summarize, herbal mixture supplements along with CC have beneficial effects on serum antioxidant levels, as well as glycemic biomarkers of infertile PCOS, menstrual regulation, and pregnancy rate.

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The relationship between Vitamin D deficiency and polycystic ovary syndrome

African Health Sciences ◽

10.4314/ahs.v20i4.45 ◽

2020 ◽

Vol 20 (4) ◽

pp. 1880-6

Author(s):

Feyzi Gokosmanoglu ◽

Attila Onmez ◽

Hasan Ergenç

Keyword(s):

Vitamin D ◽

Polycystic Ovary Syndrome ◽

Vitamin D Deficiency ◽

Polycystic Ovary ◽

Serum Testosterone ◽

Dehydroepiandrosterone Sulfate ◽

Thyroid Function Tests ◽

Ovary Syndrome ◽

Group 2 ◽

Group 1

Background: Vitamin D deficiency is frequently seen in patients with polycystic ovary syndrome (PCOS) and has been shown to exhibit multiple effects on the disease process. The purpose of this study was to investigate the role of vitamin D deficiency in complex PCOS pathophysiological pathways. Methods: Two hundred sixty-seven patients with PCOS were divided into two groups Group 1 with 25(OH)D3 deficiency, and Group 2 with normal 25(OH)D3. Biochemical and hormonal parameters (androgen hormones, gonadotropins, and thyroid function tests) were compared between the two groups. Results: Eighty-six percent of the patients (n=231) were in Group 1 and 14% (n=36) in Group 2. Statistically signifi- cantly higher concentrations of serum testosterone, dehydroepiandrosterone-sulfate and LH were determined in Group 1 (p<0.05). 25(OH)D3 concentrations were negatively correlated with body mass index (r=−0.459), serum testosterone (r =−0.374) and dehydroepiandrosterone-sulfate levels (r=−0.418); (all; p< 0.05). Conclusion: The study findings show that low 25(OH)D3 levels are associated with high androgen levels in women with PCOS. Vitamin D deficiency should be considered as an additional risk factor in the development of PCOS. We think that providing vitamin D supplementation for women from identified deficiency areas can reduce the risk of PCOS development. Keywords: Polycystic ovarian syndrome; vitamin D deficiency; androgen hormones; testosterone.

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Accuracy and efficacy of diagnosis using clinical characteristics integrated with metabolomics in patients with polycystic ovary syndrome: study protocol for a randomized controlled trial

10.21203/rs.2.12197/v2 ◽

2019 ◽

Author(s):

Cheng-Ming Ni ◽

Wen-Long Huang ◽

Yan-min Jiang ◽

Juan Xu ◽

Ru Duan ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Polycystic Ovary Syndrome ◽

Clinical Characteristics ◽

Polycystic Ovary ◽

Controlled Trial ◽

Control Group ◽

Ovary Syndrome ◽

Randomized Controlled ◽

Group 2 ◽

Group 1

Abstract Background Polycystic ovary syndrome (PCOS) is defined as a complex endocrine syndrome, and the mechanisms underlying its various clinical signs and symptoms are still poorly understood. It is critical to precisely diagnose the phenotypes of PCOS in order to provide patients with individualized therapy[1, 2] . However, the criteria by which to diagnose different phenotypes, which are mostly based on symptoms, physical examination, and laboratory evaluation, remain unclear. The aim of this study is to compare the accuracy and precision of metabolomic markers with common clinical characteristics to determine a more effective way to diagnose and treat two subgroups, one based on clinical indexes and another based on metabolomic indexes[3], of PCOS patients. The effects of different the interventions based on the two subgroups will also be observed. Methods This is a prospective, multicenter, analyst-blinded, randomized controlled trial. There will be one healthy control group and two parallel experimental arms in this study: (1) people without PCOS (health control group); (2) PCOS patients diagnosed based on clinical indexes (group 1); (3) PCOS patients diagnosed based on metabolomic indexes (group 2). A total of 276 eligible people will be recruited, including 60 healthy people and 216 PCOS patients, who will be randomly assigned to different diagnosis groups in a 1:1 ratio. Patients in the two different diagnosis groups will be divided into two different subgroups based on their clinical characteristics (group 1 based on clinical indexes, group 2 based on metabolomic indexes); thereafter, they will receive a 6-month different treatment. The primary outcome for experimental groups will be the treatment effect of PCOS. Discussion The purpose of this trial is to determine whether integrated metabolomic indexes are more accurate and effective than clinical characteristics in the diagnosis of the phenotypes of reproductive females with PCOS. This trial will therefore contribute to the provision of a solid foundation for the precise clinical diagnosis of two PCOS subgroups, as well as for future research on individualized PCOS therapy.

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The frequency and structure of metabolic disorders in obese women in combination with polycystic ovary syndrome

Obesity and metabolism ◽

10.14341/omet12374 ◽

2021 ◽

Vol 18 (3) ◽

pp. 254-262

Author(s):

E. V. Bolotova ◽

A. V. Dudnikova ◽

V. A. Krutova ◽

N. S. Prosolupova

Keyword(s):

Polycystic Ovary Syndrome ◽

Metabolic Disorders ◽

Polycystic Ovary ◽

Reproductive Age ◽

Control Group ◽

Obese Women ◽

Women Of Reproductive Age ◽

Ovary Syndrome ◽

Group 2 ◽

Group 1

Background: Obesity is considered a global epidemic and is one of the most significant medical and social problems. Research in recent years shows that in 25-45% of cases of obesity, polycystic ovary syndrome (PCOS) is detected. The influence of obesity on the pathogenesis of metabolic disorders in this category of patients remains controversialAims: to determine the frequency and structure of metabolic disorders in obese women in combination with polycystic ovary syndrome (PCOS).Materials and methods: A single-center cross-sectional sample survey of women of reproductive age was conducted. The study included clinical anthropometry with measurement of body weight, height, waist circumference (OT) and hip circumference (OB), followed by calculation of body mass index (BMI) and OT/OB ratio, and measurement of blood pressure (BP). A biochemical blood test was performed, the hormonal status was examined, and an ultrasound examination of the pelvic organs was performed.Results: A survey of 136 women of reproductive age was conducted. Group 1 included obese women without PCOS (59 patients), group 2 included obese women in combination with PCOS (45 patients), and the control group included 38 healthy women. Group 1 included obese women without PCOS (59 patients), and group 2 included obese women with PCOS (45 patients), in the control group — 38 healthy women. Among group 2 patients, dyslipidemia, visceral obesity, arterial hypertension, insulin resistance, hyperinsulinemia, and hyperuricemia were significantly more common (p<0,05). Correlations between BMI and triglycerides, testosterone and total cholesterol were found (p<0,05). Obese and PCOS patients had significantly higher levels of C-reactive protein(CRP), fibrinogen, anti-Müllerian hormone (AMH), and hepatic transaminases (p<0,05). Vitamin D deficiency was detected in 13,2% of patients, and insufficiency — in 22,7% of patients. There is a statistically significant correlation between the level of 25 (OH)D and indicators of BMI, follicle-stimulating hormone, luteinizing hormone (p<0,05), the level of AMH (p=0,008).Conclusions: A high frequency of metabolic disorders in obese women in combination with PCOS has been identified, which necessitates early screening, diagnosis and treatment of these disorders to strengthen reproductive health and prevent chronic non-communicable diseases.

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