Cytokines in the follicular fluid of stimulated and non-stimulated human ovaries; is ovulation a suppressed inflammatory reaction?

Büscher, Ulrich; Chen, F.C.K.; Kentenich, H.; Schmiady, H.

doi:10.1093/humrep/14.1.162

Cited by 96 publications

(58 citation statements)

References 27 publications

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“…Whether this discrepancy can be explained by differences between PCOS patients and normal healthy women cannot be ascertained because of the relatively small sizes of both study cohorts. Since there were no differences in the circulating IL-6 levels in our cohort of PCOS patients, local IL-6 production, which is known to be expressed in the ovaries (31,32), might be affected by the GC genotype by other, as yet unknown, mechanisms, which in turn might lead to decreased ovarian androgen secretion. Further studies, however, are required to elucidate the precise role of the C-174G IL-6 promotor polymorphism on androgen production in PCOS.…”

Section: Discussionmentioning

confidence: 78%

The polycystic ovary syndrome per se is not associated with increased chronic inflammation

Möhlig

Spranger

Osterhoff

et al. 2004

European Journal of Endocrinology

158

122

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Objective: The syndrome of polycystic ovaries (PCOS) is a known risk factor for type 2 diabetes. It is not known, however, whether the increase in diabetes risk is related to endocrine abnormalities associated with PCOS such as hyperandrogenemia, or whether it is a consequence of the anthropometric or metabolic alterations frequently observed in PCOS women. Design: Since markers of inflammation are supposed to predict type 2 diabetes, interleukin-6 (IL-6) and C-reactive protein (CRP) in combination with parameters of obesity, insulin resistance and hyperandrogenism were determined in 57 PCOS women and in 20 age-matched healthy controls. In addition, the C-174G IL-6 promoter polymorphism was analyzed as a determinant in influencing IL-6, obesity, and androgen levels in women. Results: Neither CRP nor IL-6 were significantly elevated in lean or obese PCOS women compared with age-matched lean or obese controls. In PCOS patients, variables of body composition (body mass index (BMI), waist to hip ratio, dual-energy X-ray-absorptiometry fat mass) and of insulin resistance were correlated with IL-6 or CRP, while parameters of hyperandogenism were not. Multivariate linear regression analysis revealed that obesity is the dominant force, thus explaining 18% and 24% of the IL-6 or CRP levels, respectively, in PCOS women. No association of IL-6 or BMI to a certain genotype at C-174G could be demonstrated in 50 PCOS patients. The heterozygous GC genotype, however, was associated with lower androstendione levels. Metformin treatment of 9 obese, insulin-resistant PCOS patients over a period of 6 months caused a significant decrease in body weight, body fat mass and total testosterone, but showed no significant decline in IL-6 or CRP concentrations. Conclusions: In PCOS women, plasma levels of IL-6 and CRP were not increased when compared with age-and BMI-matched controls. BMI was, however, the parameter most strongly related to IL-6 and CRP in PCOS; thus PCOS-related endocrine abnormalities do not appear to activate inflammatory parameters thereby enhancing the risk of diabetes. In PCOS, the type 2 diabetes risk may, therefore, be confined to those with obesity and/or metabolic alterations rather than affecting all women suffering from the syndrome.European Journal of Endocrinology 150 525-532

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Section: Discussionmentioning

confidence: 78%

The polycystic ovary syndrome per se is not associated with increased chronic inflammation

Möhlig

Spranger

Osterhoff

et al. 2004

European Journal of Endocrinology

158

122

View full text Add to dashboard Cite

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“…Macrophages seem to play key roles in these processes [26]. Many studies conducted with women following controlled ovarian hyperstimulation have documented the presence of proinflammatory cytokines in follicles at the time of ovulation [27][28][29][30][31][32][33]. on the other hand, it is known that leptin exerts pro-inflammatory actions: it is produced by inflammatory cells, its secretion is increased by inflammatory stimuli such as iL-1, iL-6 and lipopolysaccharide (Lps), whereas it modulates white blood cells [4].…”

Section: Discussionmentioning

confidence: 99%

Serum Pattern of Circulating Adipokines throughout the Physiological Menstrual Cycle

et al. 2009

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During the last decade, studies provided evidence on the indirect or direct participation of leptin in human reproductive functions. Leptin plays a role in puberty, gonadal function, early embryogenesis and fat metabolism during pregnancy [5][6][7]. Mean circulating leptin levels are higher in women compared to men [5][6][7]. At the same time, circulating leptin levels vary during the physiological spontaneous menstrual cycle presenting with lower values during the follicular and higher values during the luteal phase [8][9][10][11][12][13]. This fact supports the notion that leptin plays an important role in female reproductive functions and it fuels questions whether leptin levels are associated with gonadotropin or ovarian steroid levels. These questions still remain open.The participation of leptin in human female reproductive functions raises the question whether other adipokines are related to these functions, too. The present study was designed to investigate the serum levels of Byron AsiMAkopouLos*, AthAnAsios MiLousis*, theodorA GiokA**, GeorGiA kABouRoMiTi**, GeorGe GiAnissLis*, Androniki TRoussA*, MArA siMopouLou*, siMoni kATeRGARi*, GreGory TRipsiAnis*, nikos nikoLeTTos*** Abstract. This study investigated the serum levels of resistin, adiponectin and leptin during the physiological menstrual cycle. sixteen women (age: 19-30 years; body mass index: 19.46-24.9) with regular menstrual cycles participated. Fasting blood samples were collected on alternate days throughout a full menstrual cycle. Mean resistin concentrations were slightly higher during the luteal phase (5.30±0.23 ng/ml) compared to the follicular (4.68±0.07 ng/ml) and midcycle (4.86±0.09 ng/ml) phases (p=0.032). Mean leptin concentrations during the follicular phase (18.14±0.28 ng/ml) were significantly lower compared to the midcycle (21.79±0.29 ng/ml, p=0.006) and luteal phases (23.75±0.64 ng/ml, p<0.001). The variation of adiponectin concentrations throughout the menstrual cycle was not significant. According to the results, circulating resistin, likewise leptin concentrations vary significantly during the physiological menstrual cycle presenting with higher values during the luteal phase. This pattern, although its physiological importance is not clear, suggests that resistin, likewise to leptin, may have a role in the regulation of cyclic female reproductive functions. The stable adiponectin concentrations throughout the menstrual cycle indicate that this adipokine probably does not play a considerable role in female reproductive functions.

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“…Among reported constituents of FF, sexual steroids may promote PRL receptor expression [38]. Proinflammatory cytokines have also been detected in FF [39], and they promote the expression of the long PRL receptor isoform in rat pulmonary fibroblasts [40]. …”

Section: Discussionmentioning

confidence: 99%

Prolactin in Ovarian Follicular Fluid Stimulates Endothelial Cell Proliferation

Castilla

García²,

Cruz³

et al. 2009

J Vasc Res

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Angiogenesis is essential for the growth and maturation of the ovarian follicle and its transition into the corpus luteum. In addition to the main proangiogenic factors, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), follicular fluid (FF) contains the hormone prolactin (PRL), which is known to promote angiogenesis in vivo. Here, we show that FF from large follicles, which contains twice the PRL level of FF from small follicles, stimulates endothelial cell proliferation to a greater extent than the latter, and that immunoneutralization of PRL prevents FF from stimulating endothelial cell proliferation. Notably, the FF increases the expression of the short and long PRL receptor isoforms in endothelial cells, and a purified PRL standard stimulates endothelial cell proliferation but only after the cells have been pretreated with FF. However, purified PRL activates the JAK2/STAT3 pathway in endothelial cells in the absence of pretreatment with FF. In summary, PRL present in the FF stimulates the proliferation of endothelial cells. This effect likely involves the upregulation of the short and long PRL receptor isoforms and is independent of PRL-induced JAK2/STAT3 signaling.

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Cytokines in the follicular fluid of stimulated and non-stimulated human ovaries; is ovulation a suppressed inflammatory reaction?

Cited by 96 publications

References 27 publications

The polycystic ovary syndrome per se is not associated with increased chronic inflammation

The polycystic ovary syndrome per se is not associated with increased chronic inflammation

Serum Pattern of Circulating Adipokines throughout the Physiological Menstrual Cycle

Prolactin in Ovarian Follicular Fluid Stimulates Endothelial Cell Proliferation

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