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Cells
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Polycystic Ovary Syndrome (PCOS): From Molecular Mechanisms to Therapeutic Opportunities
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Polycystic Ovary Syndrome (PCOS): From Molecular Mechanisms to Therapeutic Opportunities

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Reproductive Cells and Development".

Deadline for manuscript submissions: closed (15 March 2023) | Viewed by 19012

Special Issue Editors

Prof. William Atiomo

E-Mail Website
Guest Editor
College of Medicine, Mohammed Bin Rashid University Of Medicine And Health Sciences, Dubai, UAE
Interests: polycystic; ovary; syndrome; endometrial; cancer
Prof. Dr. Thozhukat Sathyapalan

E-Mail Website
Guest Editor
Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, University of Hull, Hull HU6 7RU, UK
Interests: diabetes; obesity; nutrition; insulin resistance; glucose variability; polycystic ovary syndrome (PCOS); metabolic diseases; lipid metabolism
Special Issues, Collections and Topics in MDPI journals
Dr. Mahmood AlMashhadani

E-Mail Website
Guest Editor
College of Medicine, Mohammed Bin Rashid University Of Medicine And Health Sciences, Dubai, UAE
Interests: biomarkers; bioinformatics; diabetes; chronic, microbiome

Special Issue Information

Dear Colleagues,

Polycystic ovary syndrome (PCOS) continues to remain an enigma. Although several strides have been made in our understanding of the underlying molecular mechanisms, presenting features and long-term health consequences, there remain several unanswered questions. We still do not completely understand the mechanisms of insulin resistance, how best to predict which women will respond to fertility treatment and weight loss strategies or precisely identify which women with PCOS will go on to develop some of the long-term health conditions it has been associated with (gestational diabetes, type 2 diabetes, pre-eclampsia and endometrial cancer). The molecular mechanisms underlying psychological co-morbidities are also still unclear. This Special Issue will focus on the molecular mechanisms contributing to the development of PCOS. The Issue will also cover research investigating novel therapies directed at the underlying molecular features of PCOS. Original manuscripts and review articles addressing this very important topic are most welcome as we all work in our respective roles towards the United Nations SDG3.

Prof. William Atiomo
Prof. Thozhukat Sathyapalan
Dr. Mahmood AlMashhadani
Guest Editors

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Keywords

  • Polycystic
  • Ovary
  • Syndrome
  • Mechanisms
  • Treatment

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Published Papers (5 papers)

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Research

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17 pages, 3458 KiB  
Article
HDL-Associated Proteins in Subjects with Polycystic Ovary Syndrome: A Proteomic Study
by Alexandra E. Butler, Abu Saleh Md Moin, Željko Reiner, Thozhukat Sathyapalan, Tannaz Jamialahmadi, Amirhossein Sahebkar and Stephen L. Atkin
Cells 2023, 12(6), 855; https://doi.org/10.3390/cells12060855 - 9 Mar 2023
Cited by 4 | Viewed by 2470
Abstract
Introduction. Serum lipoproteins, with the exception of high-density lipoprotein cholesterol (HDL-C), are increased in polycystic ovary syndrome (PCOS) and their levels may reflect the associated obesity and insulin resistance, but the nature of this association is not fully explained. Therefore, proteomic analysis of [...] Read more.
Introduction. Serum lipoproteins, with the exception of high-density lipoprotein cholesterol (HDL-C), are increased in polycystic ovary syndrome (PCOS) and their levels may reflect the associated obesity and insulin resistance, but the nature of this association is not fully explained. Therefore, proteomic analysis of key proteins in lipoprotein metabolism was performed. Methods. In this cohort study, plasma was collected from 234 women (137 with PCOS and 97 controls without PCOS). Somalogic proteomic analysis was undertaken for the following 19 proteins involved in lipoprotein, and particularly HDL, metabolism: alpha-1-antichymotrypsin; alpha-1-antitrypsin; apolipoproteins A-1, B, D, E, E2, E3, E4, L1, and M; clusterin; complement C3; hemopexin; heparin cofactor II; kininogen-1; serum amyloid A-1; amyloid beta A-4; and paraoxonase-1. Results. The levels of apolipoprotein E were higher in PCOS (p = 0.012). However, the other isoforms of ApoE, ApoE2, E3, and E4, did not differ when compared with controls. ApoM was lower in PCOS (p = 0.000002). Complement C3 was higher in PCOS (p = 0.037), as was heparin cofactor II (HCFII) (p = 0.0004). The levels of the other proteins associated with lipoprotein metabolism did not differ between PCOS and controls. Conclusions. These data contribute to the concern of the deleterious dyslipidemia found in PCOS, with the novel combination reported here of higher levels of ApoE, C3 and HCFII together with lower ApoM. The dysregulation of these proteins could circumvent the protective effect of HDL-C and contribute to a more atherogenic profile that may increase cardiovascular risk. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome (PCOS): From Molecular Mechanisms to Therapeutic Opportunities)
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8 pages, 270 KiB  
Article
Expression of Markers of Endometrial Receptivity in Obese Infertile PCOS Women before and after the Weight Loss Program—A Preliminary Study
by Gaber Bergant, Dzhamilyat Abdulkhalikova, Ana Šuštaršič, Borut Peterlin, Eda Vrtačnik Bokal, Aleš Maver, Mateja Videmšek and Tanja Burnik Papler
Cells 2023, 12(1), 164; https://doi.org/10.3390/cells12010164 - 30 Dec 2022
Cited by 5 | Viewed by 2037
Abstract
Obesity is an increasing worldwide problem, and it is common in women with polycystic ovaries syndrome (PCOS). It is well known that women with PCOS have lower chances of spontaneous conception as well as lower success with IVF procedures. The mechanisms by which [...] Read more.
Obesity is an increasing worldwide problem, and it is common in women with polycystic ovaries syndrome (PCOS). It is well known that women with PCOS have lower chances of spontaneous conception as well as lower success with IVF procedures. The mechanisms by which obesity causes lower fertility are not yet fully understood. The aim of the present study was to determine the effect of a lifestyle intervention weight loss program on the expression of the endometrial genes during the window of implantation (WOI). For this purpose, 15 infertile women with obesity and PCOS were included in the study. Endometrial samples were taken during the WOI before and at the end of the program, and RNASeq analysis was performed. There were no significantly differentially expressed genes before and after the weight loss program. We then compared the results of our study with previously published studies on markers of endometrial receptivity. The biomarker genes that were found to be down-regulated during the WOI in previous studies were more down-regulated after the weight loss program in the present study. Furthermore, 25% of the women who achieved the desired 5% or more weight reduction conceived spontaneously. Our study shows that weight loss might positively impact endometrial receptivity. which may lead towards the improved fertility of obese women with PCOS. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome (PCOS): From Molecular Mechanisms to Therapeutic Opportunities)
8 pages, 245 KiB  
Article
Increased Prevalence of Elevated DHEAS in PCOS Women with Non-Classic (B or C) Phenotypes: A Retrospective Analysis in Patients Aged 20 to 29 Years
by Enrico Carmina and Rosa Alba Longo
Cells 2022, 11(20), 3255; https://doi.org/10.3390/cells11203255 - 17 Oct 2022
Cited by 7 | Viewed by 3161
Abstract
It is well known that a subgroup of women with PCOS present an excessive adrenal androgen production, generally associated with ovarian hyperandrogenism. In the past, it has been impossible to correlate adrenal hyperandrogenism to any clinical or hormonal pattern of PCOS. However, adrenal [...] Read more.
It is well known that a subgroup of women with PCOS present an excessive adrenal androgen production, generally associated with ovarian hyperandrogenism. In the past, it has been impossible to correlate adrenal hyperandrogenism to any clinical or hormonal pattern of PCOS. However, adrenal androgens are strictly dependent on age and their blood values reduce by 40% in patients moving from their twenties to thirties. Due to this, serum DHEAS values are strongly influenced by the age distribution of studied populations. To avoid this bias, in this study we retrospectively analyzed the clinical and hormonal data of PCOS women in their twenties (age between 20 and 29 years). Data of 648 young hyperandrogenic women with PCOS were evaluated. Serum DHEAS was increased in a third (33%) of studied patients and was associated with higher values of testosterone (T) and androstenedione (A). In each phenotype, patients with high DHEAS had higher values of T and A than patients with normal DHEAS of the same phenotype. Therefore, a DHEAS increase is generally part of a generalized higher androgen production in a subgroup of PCOS patients, independently of the finding of anovulatory or ovulatory cycles or of polycystic or normal ovaries. However, our study showed some important differences between PCOS phenotypes. A lower prevalence of increased DHEAS in A phenotype PCOS patients who generally have the highest androgen levels, versus non-classic (B or C) PCOS phenotypes, was observed. It was also found that patients with A phenotype PCOS present significantly lower BMI and serum insulin than patients with normal DHEAS of the same phenotype while, in patients with the B or C phenotype, the opposite occurs. We conclude that adrenal hyperandrogenism is more common in patients with non-classic (B and C) phenotypes of PCOS and is generally part of a generalized higher production of androgens in a subgroup of PCOS patients. However, other factors may increase the adrenal androgen production and influence the clinical expression of the syndrome. More studies in large, selected for age, populations of PCOS women with different phenotypes are needed. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome (PCOS): From Molecular Mechanisms to Therapeutic Opportunities)

Review

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13 pages, 620 KiB  
Review
Polycystic Ovary Syndrome and Endometrial Cancer: A Scoping Review of the Literature on Gut Microbiota
by Amog Prakash, Milad Nourianpour, Abiola Senok and William Atiomo
Cells 2022, 11(19), 3038; https://doi.org/10.3390/cells11193038 - 28 Sep 2022
Cited by 4 | Viewed by 3040
Abstract
Gut dysbiosis has been associated with polycystic ovary syndrome (PCOS) and endometrial cancer (EC) but no studies have investigated whether gut dysbiosis may explain the increased endometrial cancer risk in polycystic ovary syndrome. The aim of this scoping review is to evaluate the [...] Read more.
Gut dysbiosis has been associated with polycystic ovary syndrome (PCOS) and endometrial cancer (EC) but no studies have investigated whether gut dysbiosis may explain the increased endometrial cancer risk in polycystic ovary syndrome. The aim of this scoping review is to evaluate the extent and nature of published studies on the gut microbiota in polycystic ovary syndrome and endometrial cancer and attempt to find any similarities between the composition of the microbiota. We searched for publications ranging from the years 2016 to 2022, due to the completion date of the ‘Human Microbiome Project’ in 2016. We obtained 200 articles by inputting keywords such as ‘gut microbiome’, ‘gut microbiota’, ‘gut dysbiosis’, ‘PCOS’, and ‘endometrial cancer’ into search engines such as PubMed and Scopus. Of the 200 identified in our initial search, we included 25 articles in our final review after applying the exclusion and inclusion criteria. Although the literature is growing in this field, we did not identify enough published studies to investigate whether gut dysbiosis may explain the increased EC risk in PCOS. Within the studies identified, we were unable to identify any consistent patterns of the microbiome similarly present in studies on women with PCOS compared with women with EC. Although we found that the phylum Firmicutes was similarly decreased in women with PCOS and studies on women with EC, there was however significant variability within the studies identified making it highly likely that this may have arisen by chance. Further research pertaining to molecular and microbiological mechanisms in relation to the gut microbiome is needed to elucidate a greater understanding of its contribution to the pathophysiology of endometrial cancer in patients with polycystic ovarian syndrome. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome (PCOS): From Molecular Mechanisms to Therapeutic Opportunities)
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36 pages, 19362 KiB  
Review
Cannabinoids and PPAR Ligands: The Future in Treatment of Polycystic Ovary Syndrome Women with Obesity and Reduced Fertility
by Piotr Przybycień, Danuta Gąsior-Perczak and Wojciech Placha
Cells 2022, 11(16), 2569; https://doi.org/10.3390/cells11162569 - 18 Aug 2022
Cited by 14 | Viewed by 7413
Abstract
Cannabinoids (CBs) are used to treat chronic pain, chemotherapy-induced nausea and vomiting, and multiple sclerosis spasticity. Recently, the medicinal use of CBs has attracted increasing interest as a new therapeutic in many diseases. Data indicate a correlation between CBs and PPARs via diverse [...] Read more.
Cannabinoids (CBs) are used to treat chronic pain, chemotherapy-induced nausea and vomiting, and multiple sclerosis spasticity. Recently, the medicinal use of CBs has attracted increasing interest as a new therapeutic in many diseases. Data indicate a correlation between CBs and PPARs via diverse mechanisms. Both the endocannabinoid system (ECS) and peroxisome proliferator-activated receptors (PPARs) may play a significant role in PCOS and PCOS related disorders, especially in disturbances of glucose-lipid metabolism as well as in obesity and fertility. Taking into consideration the ubiquity of PCOS in the human population, it seems indispensable to search for new potential therapeutic targets for this condition. The aim of this review is to examine the relationship between metabolic disturbances and obesity in PCOS pathology. We discuss current and future therapeutic interventions for PCOS and related disorders, with emphasis on the metabolic pathways related to PCOS pathophysiology. The link between the ECS and PPARs is a promising new target for PCOS, and we examine this relationship in depth. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome (PCOS): From Molecular Mechanisms to Therapeutic Opportunities)
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