scholarly journals Elevated levels of arachidonic acid metabolites in follicular fluid of PCOS patients

Reproduction ◽  
2020 ◽  
Vol 159 (2) ◽  
pp. 159-169 ◽  
Author(s):  
Shengxian Li ◽  
Jia Qi ◽  
Yongzhen Tao ◽  
Qinling Zhu ◽  
Rong Huang ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Follicular Fluid ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
Pathophysiological Mechanism ◽  
Obese Women ◽  
Liquid Chromatography Mass Spectrometry ◽  
Acid Metabolites ◽  
Cox 2

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women usually accompanied by lipid metabolic disorders. However, it remains unknown whether arachidonic acid (AA) and its metabolites in follicular fluid (FF) were altered in PCOS patients. This study was intended to measure the levels of AA and its metabolites in the FF of non-obese PCOS patients that underwent in vitro fertilization (IVF) and to explore the possible causes of the alterations. Thirty-nine non-obese women with PCOS and 30 non-obese women without PCOS were enrolled. AA and its metabolites were measured by liquid chromatography-mass spectrometry. The levels of AA metabolites generated via cyclooxygenase-2 (COX-2) pathway and cytochrome P450 epoxygenase pathway but not lipoxygenase (LOX) pathway were significantly higher in the FF of PCOS patients. The metabolites generated via COX-2 pathway were significantly correlated with levels of testosterone and fasting insulin in serum. The in vitro study further demonstrated that insulin but not testosterone could promote the IL-1β and hCG-induced COX-2 expression and prostaglandin E2 (PGE2) secretion in primary human granulosa cells. In conclusion, there was an elevation in AA metabolites in FF of PCOS patients. Insulin played a pivotal role in the increased AA metabolites generated via COX-2, which could be interpreted as another novel molecular pathophysiological mechanism of PCOS.

Vaspin, a novel adipokine in woman granulosa cells physiology and PCOS pathogenesis?

2021 ◽  
Author(s):  
Alice Bongrani ◽  
Namya Mellouk ◽  
Christelle Ramé ◽  
Marion Cornuau ◽  
Fabrice Guerif ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Granulosa Cells ◽  
Follicular Fluid ◽  
Polycystic Ovary ◽  
Normal Weight ◽  
Human Reproduction ◽  
In Vitro Fertilisation ◽  
Obese Women ◽  
Human Ovary

Vaspin is a novel adipokine mainly expressed in visceral adipose tissue and closely related to obesity and insulin-resistance. Currently, data about its ovarian expression are limited to animal models and its role in human reproduction is largely unexplored. Our study’s aims were thento characterise vaspin expression in the human ovary and to study in vitro its effects on granulosa cells physiology. Secondly, we assessed vaspin and its receptor GRP78 variations in granulosa cells and follicular fluid of a cohort of 112 infertile women undergoing an in vitro fertilisation procedure and allocated to 3 groups, each including normal-weight and obese subjects: 34 PCOS patients, 33 women with isolated polycystic ovary morphology (ECHO group) and 45 controls. Vaspin and GRP78 expression in the ovary was assessed by immunohistochemistry, RT-qPCR and Western blot. Granulosa cells and follicular fluid were analysed by RT-qPCR and ELISA, respectively. In vitro, granulosa cells metabolism was studied after stimulation with recombinant human vaspin, with and without a small interfering RNA directed against GRP78. Vaspin was highly expressed in the human ovary and concentration-dependently enhanced granulosa cells steroidogenesis, proliferation and viability through GRP78 (p<0.0001). Vaspin levels in both granulosa cells and follicular fluid were significantly higher in obese women (p<0.0001) and in the normal-weight ECHO group (p<0.001), which also had the highest expression rates of GRP78 (p<0.05).Although further investigation is needed, vaspin appears as a novel modulator of human granulosa cells physiology and possibly plays a role in PCOS pathogenesis, notably protecting from insulin-resistance induced complications.

scholarly journals In vitro evidence that hyperglycemia stimulates tumor necrosis factor-α release in obese women with polycystic ovary syndrome

2006 ◽  
Vol 188 (3) ◽  
pp. 521-529 ◽  
Author(s):  
F González ◽  
N S Rote ◽  
J Minium ◽  
J P Kirwan
Keyword(s):  
Tumor Necrosis Factor ◽  
Polycystic Ovary Syndrome ◽  
Tumor Necrosis ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
Plasma Testosterone ◽  
Obese Women ◽  
Ovary Syndrome ◽  
Necrosis Factor

Women with polycystic ovary syndrome (PCOS) are often insulin resistant and have chronic low-level inflammation. The purpose of this study was to determine the effects of hyperglycemia in vitro on tumor necrosis factor (TNF)-α release from mononuclear cells (MNC) in PCOS. Twelve reproductive-age women with PCOS (six lean, six obese) and 12 age-matched controls (six lean, six obese) were studied. Insulin sensitivity (ISHOMA) was estimated from fasting levels of glucose and insulin and percent truncal fat was determined by dual energy absorptiometry (DEXA). TNFα release was measured from MNC cultured under euglycemic and hyperglycemic conditions. ISHOMA was higher in obese women with PCOS than in lean women with PCOS (student’s t-test; 73.7 ± 14.8 vs 43.1 ± 8.6, P < 0.05), but similar to that of obese controls. ISHOMA was positively correlated with percent truncal fat (r=0.57, P < 0.04). Obese women with PCOS exhibited an increase in the percent change in TNFα release from MNC in response to hyperglycemia compared with obese controls (10 mM, 649 ± 208% vs 133 ± 30%, P < 0.003; 15 mM, 799 ± 347% vs 183 ± 59%, P < 0.04). The TNFα response directly correlated with percent truncal fat (r=0.45, P < 0.03) and ISHOMA (r=0.40, P < 0.05) for the combined groups, and with plasma testosterone (r=0.60, P < 0.05) for women with PCOS. MNC of obese women with PCOS exhibit an increased TNFα response to in vitro physiologic hyperglycemia. MNC-derived TNFα release may contribute to insulin resistance and hyperandrogenism, particularly when the combination of PCOS and increased adiposity is present.

Arachidonic acid metabolites induced β-adrenoceptor densitization in rat lung in vitro

1985 ◽  
Vol 30 (5) ◽  
pp. 799-809 ◽  
Author(s):  
Luisa Daffonchio ◽  
Maria Pia Abbracchio ◽  
Alicia Hernandez ◽  
Emanuela Giani ◽  
Flaminio Cattabeni ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Rat Lung ◽  
Arachidonic Acid Metabolites ◽  
Acid Metabolites

Control of gap junction formation in canine trachea by arachidonic acid metabolites

1986 ◽  
Vol 250 (3) ◽  
pp. C495-C505 ◽  
Author(s):  
R. Agrawal ◽  
E. E. Daniel
Keyword(s):  
Arachidonic Acid ◽  
Gap Junctions ◽  
Gap Junction ◽  
Direct Effects ◽  
Leukotriene C4 ◽  
Lipoxygenase Pathway ◽  
Junction Formation ◽  
Acid Metabolites ◽  
Pg E2

This study examined whether the synthesis of the metabolites of arachidonic acid (AA) was involved in gap junction formation by 4-aminopyridine (4-AP) treatment in vitro in canine trachealis. Studies were made of the effects on gap junction formation of putative inhibitors of the cyclooxygenase and of both this and the lipoxygenase pathway of AA metabolism and the direct effects of prostaglandins (PG) E2 and I2. The number of gap junctions of similar size was increased after brief exposure to 4-AP. After indomethacin (IDM), 4-AP treatment decreased the number of gap junctions but did not affect their size. Pretreatment with 5,8,11,14-eicosatetraynoic acid or nordihydroguiaretic acid, putative inhibitors of cyclooxygenase and lipoxygenase enzymes, inhibited both the 4-AP-induced increase and decrease in the number of gap junctions. FPL 55712, a putative antagonist of leukotriene C4, did not alter either the number or the size of gap junctions when added alone or in combination with IDM. AA alone increased the number of gap junctions, but after IDM, AA decreased the number of gap junctions compared with the controls. Incubation of trachealis strips in vitro for 30 min with PGE2 increased the number of gap junctions by about threefold along with an increase in the size of the gap junctions. Similar incubation with PGI2, however, increased the number of gap junctions by approximately 60% without any change in the size. In the course of some control experiments, an interaction between carbachol and alcohol was observed such that alcohol caused an IDM-sensitive relaxation of carbachol-induced contractions, which was not observed when serotonin was the contractile agent. These results strongly suggest that PGE2 and PGI2 increase the formation of gap junctions in canine trachealis and that these prostanoids are released by 4-AP treatment. Leukotrienes may also be inhibitory in the formation of gap junctions, but FPL 55712 did not affect either the increase or the decrease in gap junctions after 4-AP.

scholarly journals Correlation of in vitro fertilization (IVF) infertility treatment outcomes and body weight index in women of reproductive age

2021 ◽  
Vol 67 (1) ◽  
pp. 76-82
Author(s):  
A. S. Druzhinina ◽  
I. I. Vitiazeva ◽  
D. A. Dimitrova
Keyword(s):  
Body Weight ◽  
Spontaneous Abortion ◽  
Polycystic Ovary ◽  
Statistical Significance ◽  
Reproductive Age ◽  
Research Centre ◽  
Class Iii ◽  
Menstrual Dysfunction ◽  
Ivf Outcomes

Backgraund: obesity/overweight in women are often the causes of menstrual dysfunction and infertility.Aims: To identify the association between overweight/obesity and IVF outcomes.Materials and methods: retrospective study — data of 1874 patients undergoing IVF in the Endocrinology Research Centre (2012–2019) was analyzed. Exclusion criteria: BMI <18.5 kg/m2, polycystic ovary syndrome, donation of ­oocytes, ectopic pregnancy, fertilization with partner’s epididymal/testicular sperm. The study included 1583 women aged 21–45 years (median 33.0 y.o. [30.0; 37.0], median BMI 23 kg/m2 [20.7; 26.2]). Statistical data processing was performed using the STATISTICA application package (StatSoft). The threshold level of statistical significance is <0.05.Results: Patients were divided into 5 groups (gr.): normal body weight (NBW) - 1061 people (ppl.) (gr. 1), overweight — 368 (gr. 2), class I obesity — 117 (gr. 3), class II obesity — 36 (gr. 4), class III obesity — 1 (gr. 5). In each group, the estimated pregnancy rate (PR) and its outcomes, the frequency of lightweight newborns (body weight at birth <2500g), newborns with NBW (2500-3999g), births with a large fetus (≥4000g) were measured. The PR didn’t differ: 34.6%, 34.5%, 30,7%, 41,7%, respectively, the woman in gr.5 got pregnant. Among 407 (74.4%) singleton pregnancies urgent delivery was registered in 71.91%, 67,57%, 70,83%, 60,0%, gr. 5 — no ­information. Premature birth: 7,66%, 5,41%, 8,33%, 0%. Spontaneous abortion in the 1st trimester: 18,30%, 25,68%, 20,83%, 40,0%. Spontaneous abortion in the 2nd trimester: 2,13%, 1,35% in gr. 2, 3, 4. Lightweight newborns: 8,81%, 11,36%, 6,25%, 0%. Newborns with NBW: 84,91%, 84,09%, 75,0%, 60,0%. Large-childbirth — 6,29%, 4,55%, 18,75%, 40,0%.Conclusions: Correlation analysis of the dependence of PR and its outcomes on the BMI was not revealed (p=0.975 and p=0.469, respectively). Large fetus births were more often detected in obese patients (p=0.0016). A large prospective group is needed to expand the estimated body parameters to the IVF outcomes.

Obesity and oocyte quality: Significant implications for ART and Emerging mechanistic insights

2021 ◽  
Author(s):  
Macarena B Gonzalez ◽  
Rebecca L Robker ◽  
Ryan D Rose
Keyword(s):  
Pregnancy Complications ◽  
Maternal Obesity ◽  
Ovarian Function ◽  
Polycystic Ovary ◽  
Live Birth Rate ◽  
Oocyte Quality ◽  
Reproductive Age ◽  
Developmental Competence ◽  
Obese Women ◽  
Increased Risk

Abstract The prevalence of obesity in adults worldwide, and specifically in women of reproductive age, is concerning given the risks to fertility posed by the increased risk of type 2 diabetes, metabolic syndrome and other non-communicable diseases. Obesity has a multi-systemic impact in female physiology that is characterized by the presence of oxidative stress, lipotoxicity, and the activation of pro-inflammatory pathways, inducing tissue-specific insulin resistance and ultimately conducive to abnormal ovarian function. A higher body mass is linked to Polycystic Ovary Syndrome, dysregulated menstrual cycles, anovulation, and longer time to pregnancy, even in ovulatory women. In the context of ART, compared to women of normal BMI, obese women have worse outcomes in every step of their journey, resulting in reduced success measured as live birth rate. Even after pregnancy is achieved, obese women have a higher chance of miscarriage, gestational diabetes, pregnancy complications, birth defects, and most worryingly, a higher risk of stillbirth and neonatal death. The potential for compounding effects of ART on pregnancy complications and infant morbidities in obese women has not been studied. There is still much debate in the field on whether these poorer outcomes are mainly driven by defects in oocyte quality, abnormal embryo development or an unaccommodating uterine environment, however the clinical evidence to date suggests a combination of all three are responsible. Animal models of maternal obesity shed light on the mechanisms underlaying the effects of obesity on the peri-conception environment, with recent findings pointing to lipotoxicity in the ovarian environment as a key driver of defects in oocytes that have not only reduced developmental competence but long-lasting effects in offspring health.

scholarly journals A review of therapeutic options for managing the metabolic aspects of polycystic ovary syndrome

2020 ◽  
Vol 11 ◽  
pp. 204201882093830 ◽  
Author(s):  
Mohammed Altigani Abdalla ◽  
Harshal Deshmukh ◽  
Stephen Atkin ◽  
Thozhukat Sathyapalan
Keyword(s):  
Insulin Resistance ◽  
Weight Loss ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Therapeutic Options ◽  
Reproductive Age ◽  
Obese Women ◽  
Cardiovascular Risk Reduction ◽  
Ovary Syndrome ◽  
Incretin Mimetics

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. Metabolic sequelae associated with PCOS range from insulin resistance to type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Insulin resistance plays a significant role in the pathophysiology of PCOS and it is a reliable marker for cardiometabolic risk. Although insulin sensitising agents such as metformin have been traditionally used for managing metabolic aspects of PCOS, their efficacy is low in terms of weight reduction and cardiovascular risk reduction compared with newer agents such as incretin mimetics and SGLT2 inhibitors. With current pharmaceutical advances, potential therapeutic options have increased, giving patients and clinicians more choices. Incretin mimetics are a promising therapy with a unique metabolic target that could be used widely in the management of PCOS. Likewise, bariatric procedures have become less invasive and result in effective weight loss and the reversal of metabolic morbidities in some patients. Therefore, surgical treatment targeting weight loss becomes increasingly common in the management of obese women with PCOS. Newer emerging therapies, including twincretins, triple GLP-1 agonists, glucagon receptor antagonists and imeglemin, are promising therapeutic options for treating T2DM. Given the similarity of metabolic and pathological features between PCOS and T2DM and the variety of therapeutic options, there is the potential to widen our strategy for treating metabolic disorders in PCOS in parallel with current therapeutic advances. The review was conducted in line with the recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome 2018.

Sign in / Sign up

Export Citation Format

Share Document