-
Frontiers in Endocrinology 2023This article reviewed the relationship between the autonomic nervous system and the development of polycystic ovary syndrome (PCOS). PCOS is the most common reproductive... (Review)
Review
This article reviewed the relationship between the autonomic nervous system and the development of polycystic ovary syndrome (PCOS). PCOS is the most common reproductive endocrine disorder among women of reproductive age. Its primary characteristics include persistent anovulation, hyperandrogenism, and polycystic ovarian morphology, often accompanied by disturbances in glucose and lipid metabolism. The body's functions are regulated by the autonomic nervous system, which consists mainly of the sympathetic and parasympathetic nervous systems. The autonomic nervous system helps maintain homeostasis in the body. Research indicates that ovarian function in mammals is under autonomic neural control. The ovaries receive central nervous system information through the ovarian plexus nerves and the superior ovarian nerves. Neurotransmitters mediate neural function, with acetylcholine and norepinephrine being the predominant autonomic neurotransmitters. They influence the secretion of ovarian steroids and follicular development. In animal experiments, estrogen, androgens, and stress-induced rat models have been used to explore the relationship between PCOS and the autonomic nervous system. Results have shown that the activation of the autonomic nervous system contributes to the development of PCOS in rat. In clinical practice, assessments of autonomic nervous system function in PCOS patients have been gradually employed. These assessments include heart rate variability testing, measurement of muscle sympathetic nerve activity, skin sympathetic response testing, and post-exercise heart rate recovery evaluation. PCOS patients exhibit autonomic nervous system dysfunction, characterized by increased sympathetic nervous system activity and decreased vagal nerve activity. Abnormal metabolic indicators in PCOS women can also impact autonomic nervous system activity. Clinical studies have shown that various effective methods for managing PCOS regulate patients' autonomic nervous system activity during the treatment process. This suggests that improving autonomic nervous system activity may be an effective approach in treating PCOS.
Topics: Female; Humans; Rats; Animals; Polycystic Ovary Syndrome; Hyperandrogenism; Autonomic Nervous System; Neurotransmitter Agents; Mammals
PubMed: 38313837
DOI: 10.3389/fendo.2023.1295061 -
Journal of Ovarian Research Jan 2024Polycystic ovarian syndrome (PCOS) is a genetically complex disorder that involves the interplay of multiple genes and environmental factors. It is characterized by...
Polycystic ovarian syndrome (PCOS) is a genetically complex disorder that involves the interplay of multiple genes and environmental factors. It is characterized by anovulation and irregular menses and is associated with type 2 diabetes. Neuroendocrine pathways and ovarian and adrenal dysfunctions are possibly implicated in the disorder pathogenesis. The melatonin system plays a role in PCOS. Melatonin receptors are expressed on the surface of ovarian granulosa cells, and variations in the melatonin receptor genes have been associated with increased risk of PCOS in both familial and sporadic cases. We have recently reported the association of variants in MTNR1A and MTNR1B genes with familial type 2 diabetes. In this study, we aimed to investigate whether MTNR1A and MTNR1B contribute to PCOS risk in peninsular families. In 212 Italian families phenotyped for PCOS, we amplified by microarray 14 variants in the MTNR1A gene and 6 variants in the MTNR1B gene and tested them for linkage and linkage disequilibrium with PCOS. We detected 4 variants in the MTNR1A gene and 2 variants in the MTNR1B gene significantly linked and/or in linkage disequilibrium with the risk of PCOS (P < 0.05). All variants are novel and have not been reported before with PCOS or any of its related phenotypes, except for 3 variants previously reported by us to confer risk for type 2 diabetes and 1 variant for type 2 diabetes-depression comorbidity. These findings implicate novel melatonin receptor genes' variants in the risk of PCOS with potential functional roles.
Topics: Female; Humans; Polycystic Ovary Syndrome; Diabetes Mellitus, Type 2; Phenotype; Anovulation
PubMed: 38217063
DOI: 10.1186/s13048-024-01343-1 -
Journal of Ovarian Research Jan 2024For women of childbearing age, the biggest problem caused by polycystic ovary syndrome (PCOS) is infertility, which is mainly caused by anovulation, abnormal follicular...
BACKGROUND
For women of childbearing age, the biggest problem caused by polycystic ovary syndrome (PCOS) is infertility, which is mainly caused by anovulation, abnormal follicular development, proliferation of small antral follicles, and cystic follicles. The mechanism underlying its occurrence is not clear. The abnormal proliferation and development of follicles in PCOS patients is a complex process, which is affected by many factors. The objective of this study was to investigate the relationship between the Hippo pathway and follicular development in PCOS, and to further explore this relationship by using the YAP inhibitor verteporfin (VP).
METHOD
30 3-week-old BALB/C female rats were randomly divided into control group (n = 10), DHEA group (n = 10) and DHEA + VP group (n = 10). The morphology of ovary and the degree of follicular development were observed by HE staining, and the expression and location of AMH in ovarian follicles were observed by immunofluorescence. The ovarian reserve function index AMH, cell proliferation index PCNA and the ratio of Hippo pathway related proteins MST, LATS, YAP, P-YAP and P-YAP/YAP were detected by Western blot.
RESULTS
After dividing 30 3-week-old female mice into control, dehydroepiandrosterone (DHEA; model of PCOS), and DHEA + VP groups, we found that the number of small follicles increased in the DHEA group compared to the control group. Additionally, in the DHEA group compared to the control group, anti-müllerian hormone (AMH; ovarian reserve index) increased, proliferating cell nuclear antigen (PCNA; cell proliferation index) decreased, and upstream (MST and LATS) and downstream (YAP and p-YAP) proteins in the Hippo pathway increased, though the p-YAP/YAP ratio decreased. VP ameliorated the increases in AMH, MST, LATS, YAP and p-YAP, but did not ameliorate the decrease in the p-YAP/YAP ratio.
CONCLUSIONS
This study indicates that the increased small follicles in the ovaries and changes in ovarian reserve and cell proliferation may be closely related to Hippo pathway activation. This suggests that the Hippo pathway may be an important pathway affecting the proliferation and development of follicles and the occurrence of PCOS.
Topics: Humans; Female; Rats; Animals; Mice; Polycystic Ovary Syndrome; Proliferating Cell Nuclear Antigen; Hippo Signaling Pathway; Mice, Inbred BALB C; Anti-Mullerian Hormone; Dehydroepiandrosterone
PubMed: 38216976
DOI: 10.1186/s13048-023-01305-z -
PloS One 2023Polycystic Ovary Syndrome (PCOS) affects many people and is often distressing. Much medical literature about diagnosis and treatment exists, but little is known about...
Polycystic Ovary Syndrome (PCOS) affects many people and is often distressing. Much medical literature about diagnosis and treatment exists, but little is known about PCOS menstrual cycle-related experiences except that cycles tend to be far-apart and unpredictable. Our purpose was to examine the menstrual cycle and daily life experiences in those with PCOS having approximately month-apart cycles compared with age and BMI-matched cohort controls using data from the Menstruation & Ovulation Study 2 (MOS2) during the first 1.5 years of SARS-CoV-2 pandemic. We hypothesized that those with PCOS would experience lower self-worth and more negative moods. This is a single-cycle prospective case-control study in community-dwelling women ages 19-35 years. Eight reported physician-diagnosed PCOS and were matched (1:3 ratio) with controls by age (within .6 years) and BMI (within .19 BMI units). Experiences were recorded daily (Menstrual Cycle Diary©, Diary). All kept daily morning temperatures to assess luteal phase lengths by the validated Quantitative Basal Temperature© analysis method. From 112 in MOS2, 32 women were compared: eight with PCOS versus 24 controls. Demographic, socioeconomic, comorbidities and lifestyle variables were not different between the two groups. Cycle lengths were similar in PCOS and controls (one PCOS and control each had oligomenorrhea; most lengths were 21-35 days, P = .593). Unexpectedly, luteal phase lengths were also similar between PCOS and controls (P = .167); anovulation occurred in 5 with PCOS, and in 9 controls. There were no significant Diary differences between the two groups except for greater "outside stress" in the PCOS group (P = .020). In contrast to our hypotheses, there were no significant differences in feelings of self-worth, anxiety nor depression. The SARS-CoV-2 pandemic was a stressful time for women. MOS2 captured granular menstrual cycles, ovulation and daily experiences in women with PCOS compared with age- and BMI-matched controls. These pilot data in women with milder PCOS are the first of more research required to understand the daily experiences in those living with PCOS.
Topics: Female; Humans; Child; Polycystic Ovary Syndrome; SARS-CoV-2; Case-Control Studies; Molybdenum; Pandemics; COVID-19; Menstrual Cycle
PubMed: 38157371
DOI: 10.1371/journal.pone.0296377 -
Drug Discoveries & Therapeutics Jan 2024Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting fertility and mental health among women of reproductive age. In addition to anovulation and...
Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting fertility and mental health among women of reproductive age. In addition to anovulation and hyperandrogenism, patients also experience metabolic issues, such as insulin resistance, obesity, and dyslipidemia, as well as chronic low-grade inflammation throughout the body. Recent studies have shown that even with assisted reproductive technology to treat anovulatory issues, patients with PCOS still have higher rates of adverse pregnancy outcomes and abortion compared to normal pregnancies. These findings suggest that PCOS may impair the endometrium and disrupt the onset and maintenance of healthy pregnancies. Decidualization is a crucial step in the process of healthy pregnancy, during which endometrial stromal cells (ESCs) differentiate into secretory decidual stromal cells (DSCs) regulated by hormones and local metabolism. This article comprehensively reviews the pathological processes of PCOS and the mechanisms involved in its impaired decidualization. In addition, we explore how PCOS increases the incidence of adverse pregnancy outcomes (APO). By gaining a better understanding of the adverse effects of PCOS on pregnancy and its specific mechanisms, we hope to provide a theoretical basis for reducing APO and improving the live birth rate among women with PCOS.
Topics: Pregnancy; Humans; Female; Polycystic Ovary Syndrome; Hyperandrogenism; Anovulation; Insulin Resistance
PubMed: 38148009
DOI: 10.5582/ddt.2023.01096 -
Obstetrics & Gynecology Science Jan 2024Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in women of reproductive age. The clinical symptoms include hyperandrogenism, chronic anovulation, and...
Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in women of reproductive age. The clinical symptoms include hyperandrogenism, chronic anovulation, and multiple ovarian cysts. PCOS is strongly associated with obesity and insulin resistance. MicroRNAs (miRNAs) are a group of short non-coding RNAs that play a role in the post-transcriptional regulation of gene expression and translational inhibition. They play a vital role in the regulation of multiple metabolic and hormonal processes as well as in oocyte maturation and folliculogenesis in the female reproductive system. miRNAs can be used as diagnostic biomarkers or therapeutic targets because of their stability. The encapsulation of miRNAs in extracellular vesicles or exosomes contributes to their stability. Exosomes are constantly secreted by many cells and size of about 30 to 150 nm. Enveloping miRNAs exosomes can release them for cellular communication. The induced transfer of miRNAs by exosomes is a novel process of genetic exchange between cells. Many studies have shown that along with non-exosomal miRNAs, different types of exosomal miRNAs derived from the serum and follicular fluid can play an essential role in PCOS pathogenesis. These miRNAs are involved in follicular development and various functions in granulosa cells, apoptosis, cell proliferation, and follicular atresia. The present study aimed to comprehensively review the evidence on miRNAs and their affected pathways under both non-exosomal and exosomal circumstances, primarily focusing on the pathogenesis of PCOS.
PubMed: 38050353
DOI: 10.5468/ogs.23193 -
Frontiers in Sports and Active Living 2023The release of luteinising hormone (LH) before ovulation is disrupted during a state of low energy availability (EA). However, it remains unknown whether a threshold EA...
Free-living competitive racewalkers and runners with energy availability estimates of <35 kcal·kg fat-free mass·day exhibit peak serum progesterone concentrations indicative of ovulatory disturbances: a pilot study.
INTRODUCTION
The release of luteinising hormone (LH) before ovulation is disrupted during a state of low energy availability (EA). However, it remains unknown whether a threshold EA exists in athletic populations to trigger ovulatory disturbances (anovulation and luteal phase deficiency) as indicated by peak/mid-luteal serum progesterone concentration (Pk-PRG) during the menstrual cycle.
METHODS
We assessed EA and Pk-PRG in 15 menstrual cycles to investigate the relationship between EA and Pk-PRG in free-living, competitive (trained-elite) Guatemalan racewalkers (= 8) and runners (= 7) [aged: 20 (14-41) years; post-menarche: 5 (2-26) years; height: 1.53 ± 0.09 m; mass: 49 ± 6 kg (41 ± 5 kg fat-free mass "FFM")]. EA was estimated over 7 consecutive days within the follicular phase using food, training, and physical activity diaries. A fasted blood sample was collected during the Pk-PRG period, 6-8 days after the LH peak, but before the final 2 days of each cycle. Serum progesterone concentration was quantified using electrochemiluminescence immunoassay.
RESULTS
Participants that reported an EA of <35 kcal·kg FFM·day (= 7) exhibited ovulatory disturbances (Pk-PRG ≤9.40 ng·mL). Athletes with EA ≥36 kcal·kg FFM·day (= 8) recorded "normal"/"potentially fertile" cycles (Pk-PRG >9.40 ng·mL), except for a single racewalker with the lowest reported protein intake (1.1 g·kg body mass·day). EA was positively associated with Pk-PRG [(9) = 0.79, 95% confidence interval (CI): 0.37-0.94; = 0.003; 1 - = 0.99] after excluding participants (= 4) that likely under-reported/reduced their dietary intake.
CONCLUSIONS
The result from the linear regression analysis suggests that an EA ≥ 36 kcal·kg FFM·day is required to achieve "normal ovulation." The threshold EA associated with ovulatory disturbances in athletes and non-invasive means of monitoring the ovulatory status warrant further research.
PubMed: 38046932
DOI: 10.3389/fspor.2023.1279534 -
Cureus Oct 2023In females with polycystic ovarian syndrome (PCOS), the most prevalent endocrine condition is chronic anovulation and hyperandrogenism. This illness influences females... (Review)
Review
In females with polycystic ovarian syndrome (PCOS), the most prevalent endocrine condition is chronic anovulation and hyperandrogenism. This illness influences females from conception to death, posing several risks to the health of a female, thus reducing the quality of life. It also increases the rates of mortality and morbidity. The first years of puberty are when PCOS symptoms first show. Menstrual irregularities, anovulation, and acne are features of both PCOS and typical puberty in females. There are many various phenotypes that fall under the same illness, so it is necessary to examine each one independently because they may need different treatments and result in different outcomes. Depending on the diagnostic criteria, approximately 6%-20% of females in the reproductive age group are believed to be affected by PCOS. As long as PCOS is still a syndrome, no single diagnostic indicator, such as hyperandrogenism or polycystic ovary (PCO), can be used to make a clinical diagnosis. The management of females with PCOS depends on the symptoms. These could include menstruation problems, androgen-related symptoms, or infertility caused by ovulatory disruption. In females with PCOS, anovulation is linked to low follicle-stimulating hormone (FSH) levels and a halt in antral follicle growth during the last stages of maturation. The condition may be treated surgically with laparoscopic ovarian drilling or medically with medications such as aromatase inhibitors, metformin, glucocorticoids, clomiphene citrate (CC), tamoxifen, or gonadotropins. Patients will experience different androgenic symptoms, such as hirsutism, acne, and/or baldness. Patients who appear with these troubling symptoms need to receive appropriate care. The review emphasizes the role it plays in the management of various conditions.
PubMed: 38021970
DOI: 10.7759/cureus.47408 -
Clinics (Sao Paulo, Brazil) 2023PCOS is an endocrine disorder characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries. Its etiology is uncertain. It is debated whether BPA would... (Review)
Review
PCOS is an endocrine disorder characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries. Its etiology is uncertain. It is debated whether BPA would be a component of the environmental factor in the etiology of PCOS. Contamination by BPA can occur from food packaging (exposure during the diet) and through skin absorption and/or inhalation. It can be transferred to the fetus via the placenta or to the infant via breast milk, and it can be found in follicular fluid, fetal serum, and amniotic fluid. The phenolic structure of BPA allows it to interact with Estrogen Receptors (ERs) through genomic signaling, in which BPA binds to nuclear ERα or Erβ, or through nongenomic signaling by binding to membrane ERs, prompting a rapid and intense response. With daily and constant exposure, BPA's tendency to bioaccumulate and its ability to activate nongenomic signaling pathways can alter women's metabolic and reproductive function, leading to hyperandrogenism, insulin resistance, obesity, atherogenic dyslipidemia, chronic inflammatory state, and anovulation and favoring PCOS. The harmful changes caused by BPA can be passed on to future generations without the need for additional exposure because of epigenetic modifications. Not only high BPA levels can produce harmful effects, but at low levels, BPA may be harmful when exposure occurs during the most vulnerable periods, such as the fetal and neonatal periods, as well as during the prepubertal age causing an early accumulation of BPA in the body. Learning how BPA participates in the pathogenesis of PCOS poses a challenge and further studies should be conducted.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Polycystic Ovary Syndrome; Hyperandrogenism; Anovulation; Phenols
PubMed: 38008036
DOI: 10.1016/j.clinsp.2023.100310 -
Reproductive Biology and Endocrinology... Nov 2023Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women. This disorder affects 6-15% of women of childbearing age worldwide. It is diagnosed with...
BACKGROUND
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women. This disorder affects 6-15% of women of childbearing age worldwide. It is diagnosed with hyperandrogenism, polycystic ovaries, and chronic anovulation with insulin resistance. This study aimed to assess the prevalence of insulin resistance (IR) in 4 phenotypes of PCOS, and its relationship with demographic, clinical, and paraclinical individual characteristics in a sample of Iranian PCOS patients.
METHODS
This particular cross-sectional investigation involved 160 female participants, aged between 18 and 45 years, who were receiving care at gynecology clinics in Urmia, northwestern Iran. All the participants had been diagnosed with PCOS and were categorized into one of four phenotypes. All the participants underwent clinical evaluations, paraclinical assessments, and ultrasound scans. IR was defined as HOMA-IR > 2.5. The statistical significance level was 0.05.
RESULTS
Among the 160 participants, the prevalences of the 4 phenotypes were: A: 83 (51.9%), B: 37 (23.1%), C: 21 (13.1%), and D: 19 (11.9%). IR was detected in 119 participants (74.4%); its rate was significantly different between the 4 phenotypes (p-value: 0.008) as A: 62 (74.7%), B: 34 (91.9%), C: 12 (57.1%), D: 11 (57.9%). Linear and logistic regression analyses were performed to control confounding factors. In linear regression, PCOS phenotype, classic phenotype (A&B), economic status, and Hb levels were significantly related to HOMA-IR; in logistic regression Hb levels, exercise, economic status, and PCOS phenotypes were significantly associated with insulin resistance.
CONCLUSIONS
The most prevalent PCOS phenotype in this study was A. PCOS phenotypes were significantly related to insulin resistance and HOMA-IR, with the highest levels of insulin resistance and HOMA-IR observed in phenotype B. Determining the phenotype of PCOS may be helpful for better management of PCOS and its associated complications. However, further investigations are recommended in this regard.
Topics: Humans; Female; Adolescent; Young Adult; Adult; Middle Aged; Polycystic Ovary Syndrome; Insulin Resistance; Cross-Sectional Studies; Iran; Phenotype; Insulin
PubMed: 38001527
DOI: 10.1186/s12958-023-01160-z