Alterations of polyunsaturated fatty acid metabolism in ovarian tissues of polycystic ovary syndrome rats

Huang, Rong; Xue, Xinli; Li, Shengxian; Wang, Yuying; Sun, Yun; Liu, Wei; Yin, Huiyong; Tao, Tao

doi:10.1111/jcmm.13614

Cited by 18 publications

(11 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We previously reported the diminished AA metabolites in the serum of PCOS patients (Li et al 2017) and elevated COX-2 expression in ovaries of PCOS rats (Huang et al 2018). Here we further clarified that AA metabolites via COX-2 were also increased in FF of PCOS patients, which was consistent with the rat model results.…”

Section: Discussionmentioning

confidence: 96%

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

Jia

Tao

et al. 2020

Reproduction

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 96%

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

Jia

Tao

et al. 2020

Reproduction

Self Cite

View full text Add to dashboard Cite

show abstract

“…It has been demonstrated that abnormal COX-2 levels are associated with ovulation failure, infertility, and implantation disorders [ 23 ]. In a rat model study, it was shown that the levels of PG and metabolites of AA (via the COX pathway) were significantly higher in the ovarian tissue of the PCOS group than in that of the healthy control group [ 24 ]. In turn, human studies have shown a significant increase in the 9-HODE/13-HODE serum level among patients with PCOS [ 25 ].…”

Section: Participation Of Aa Metabolites In Fertilitymentioning

confidence: 99%

The Role of Arachidonic and Linoleic Acid Derivatives in Pathological Pregnancies and the Human Reproduction Process

Szczuko

Kikut

Komorniak

et al. 2020

IJMS

View full text Add to dashboard Cite

The aim of the available literature review was to focus on the role of the proinflammatory mediators of AA and LA derivatives in pathological conditions related to reproduction and pregnancy. Arachidonic (AA) and linoleic acid (LA) derivatives play important roles in human fertility and the course of pathological pregnancies. Recent studies have demonstrated that uncontrolled inflammation has a significant impact on reproduction, spermatogenesis, endometriosis, polycystic ovary syndrome (PCOS) genesis, implantation, pregnancy and labor. In addition, cyclooxygenase-mediated prostaglandins and AA metabolite levels are higher in women’s ovarian tissue when suffering from PCOS. It has been demonstrated that abnormal cyclooxygenase-2 (COX-2) levels are associated with ovulation failure, infertility, and implantation disorders and the increase in 9-HODE/13-HODE was a feature recognized in PCOS patients. Maintaining inflammation without neutrophil participation allows pregnant women to tolerate the fetus, while excessive inflammatory activation may lead to miscarriages and other pathological complications in pregnancies. Additionally AA and LA derivatives play an important role in pregnancy pathologies, e.g., gestational diabetes mellitus, preeclampsia (PE), and fetal growth, among others. The pathogenesis of PE and other pathological states in pregnancy involving eicosanoids have not been fully identified. A significant expression of 15-LOX-1,2 was found in women with PE, leading to an increase in the synthesis of AA and LA derivatives, such as hydroxyeicozatetraenoic acids (HETE) and hydroxyoctadecadiene acids (HODE). Synthesis of the metabolites 5-, 8-, 12-, and 15-HETE increased in the placenta, while 20-HETE increased only in umbilical cord blood in women with preeclampsia compared to normal pregnancies. In obese women with gestational diabetes mellitus (GDM) an increase in epoxygenase products in the cytochrome P450 (CYP) and the level of 20-HETE associated with the occurrence of insulin resistance (IR) were found. In addition, 12- and 20-HETE levels were associated with arterial vasoconstriction and epoxyeicosatrienoic acids (EETs) with arterial vasodilatation and uterine relaxation. Furthermore, higher levels of 5- and 15-HETE were associated with premature labor. By analyzing the influence of free fatty acids (FFA) and their derivatives on male reproduction, it was found that an increase in the AA in semen reduces its amount and the ratio of omega-6 to omega-3 fatty acids showed higher values in infertile men compared to the fertile control group. There are several studies on the role of HETE/HODE in relation to male fertility. 15-Hydroperoxyeicosatetraenoic acid may affect the integrity of the membrane and sperm function. Moreover, the incubation of sperm with physiologically low levels of prostaglandins (PGE2/PGF2α) improves the functionality of human sperm. Undoubtedly, these problems are still insufficiently understood and require further research. However, HETE and HODE could serve as predictive and diagnostic biomarkers for pregnancy pathologies (especially in women with risk factors for overweight and obesity). Such knowledge may be helpful in finding new treatment strategies for infertility and the course of high-risk pregnancies.

show abstract

“…Elevated circulatory concentrations of OA were correlated with the adverse pregnancy outcomes in obese women with PCOS undergoing controlled ovarian hyperstimulation [14]. Huang et al 2018 [55] showed that PCOS affects the metabolism of UFAs in rats. In particular, metabolites of AA generated by the cyclooxygenase enzyme were significantly increased in the ovaries of PCOS rats.…”

Section: Unsaturated Fatty Acidsmentioning

confidence: 99%

Non-esterified fatty acids in the ovary: friends or foes?

Baddela

Sharma

Vanselow

2020

Reprod Biol Endocrinol

View full text Add to dashboard Cite

A majority of common metabolic diseases can result in excessive lipolysis, leading to elevated levels of non-esterified fatty acids (NEFAs) in the body fluids. In females, increased NEFA levels in the follicular fluid markedly alter the functions of intrafollicular cells such as granulosa cells (GCs) and oocytes. Therefore, elevated levels of NEFAs have been suggested to be a significant player of subfertility in females of both human and economically important animal species such as cattle, buffalo, sheep, pig, chicken, and dog. However, the effects imposed by saturated and unsaturated fatty acids (SFAs and UFAs) on ovarian follicles are controversial. The present review emphasizes that SFAs induce apoptosis in granulosa and cumulus cells of ovarian follicles in different species. They further could adversely affect oocyte maturation and developmental competence. Many types of UFAs affect steroidogenesis and proliferation processes and could be detrimental for follicular cells, especially when at elevated concentrations. Interestingly, monounsaturated fatty acids (MUFAs) appear to contribute to the etiology of the polycystic ovarian syndrome (PCOS) as they were found to induce the transcription and translation of the androgenic transcription factor SOX9 while downregulating its estrogenic counterpart FOXL2 in GCs. Overall, this review presents our revised understanding of the effects of different fatty acids on the female reproductive success, which may allow other researchers and clinicians to investigate the mechanisms for treating metabolic stress-induced female infertility.

show abstract

Alterations of polyunsaturated fatty acid metabolism in ovarian tissues of polycystic ovary syndrome rats

Cited by 18 publications

References 39 publications

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

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

The Role of Arachidonic and Linoleic Acid Derivatives in Pathological Pregnancies and the Human Reproduction Process

Non-esterified fatty acids in the ovary: friends or foes?

Contact Info

Product

Resources

About