Differential expression of inflammation-related genes in the ovarian stroma and granulosa cells of PCOS women

Abstract

Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder. Ovarian changes in PCOS women are well characterized by ultrasound. However, the ovarian pathophysiology is not fully understood. The aim of this study was to characterize the expression, in both the central ovarian stroma and in granulosa cells (GCs), of a number of genes, including several inflammation-related genes, which have been hypothesized to be involved in the pathophysiology of PCOS. Biopsies of the central ovarian stroma were obtained from PCOS women (Rotterdam criteria) and from normally ovulating women in follicular phase. GCs were retrieved from PCOS-women and non-PCOS women, undergoing in vitro maturation. The expressions of 57 genes were analyzed by quantitative-PCR using a low-density-gene array. The main outcome measures were over-expression or under-expression of the specific genes. The results showed that in the central stroma of PCOS ovaries, five inflammation-related genes (CCL2, IL1R1, IL8, NOS2, TIMP1), the leukocyte marker CD45, the inflammation-related transcription factor RUNX2 and the growth factor AREG were under-expressed. The growth factor DUSP12 and the coagulation factor TFPI2 were over-expressed. In the GC of PCOS, all of the differentially expressed genes were over-expressed; the inflammation-related IL1B, IL8, LIF, NOS2 and PTGS2, the coagulation-related F3 and THBS1, the growth factors BMP6 and DUSP12, the permeability-related AQ3 and the growth-arrest-related GADD45A. In conclusion, the results indicate major alterations in the local ovarian immune system of PCOS ovaries. This may have implications for the PCOS-related defects in the inflammation-like ovulatory process and for the susceptibility to acquire the inflammatory state of ovarian hyperstimulation syndrome.

Luteinizing hormone/chorionic gonadotrophin receptor overexpressed in granulosa cells from polycystic ovary syndrome ovaries is functionally active

“…This is consistent with a previous report that GCs from PCOS patients are more responsive to LH in terms of oestradiol and progesterone production than GCs from normal women (Willis et al, 1998). Increased LHCGR activity may also be responsible for the overexpression of aquaporins in PCOS, given that excessive fluid permeability is one of the features of severe OHSS (Schmidt et al, 2014).…”

“…Although the clinical and biochemical features of PCOS are well described, our paper provides novel and unique insight into the regulation of LHCGR receptor in granulosa cells of normal and PCOS women. Women with PCOS are at greater risk of developing OHSS after controlled ovarian hyperstimulation using gonadotropins for IVF (Schmidt et al, 2014). We provide evidence here that overexpression of functional LHCGR in GCs of PCOS is likely to be part of the mechanism of OHSS.…”

“…Interestingly, a number of genes involved in gonadotrophic response, steroidogenesis and water permeability e.g. growth factors (BMP6), amphiregulin (AREG) and aquaporins (AQP3) are upregulated in PCOS follicles (Schmidt et al, 2014) but the functional significance of these changes remains to be investigated.…”

Profiling cancer testis antigens in non–small-cell lung cancer

“…An additional potential source of discrepancies could be tissues affected by inflammation, leading to a change of tissue composition and consequently the expression profile. Surprisingly, we identified and excluded only one gene (TFPI2) due to effects likely related to inflammation (38,39). Furthermore, the coexpression analyses demonstrate that newly identified CTAs largely group together with established CTAs, indicating a similar regulatory mechanism and coordinated expression, which is a known feature of CTAs (22,40,41).…”

Granulosa cell biomarkers to predict pregnancy in ART: pieces to solve the puzzle

“…PCOS compared to non-PCOS (Catteau-Jonard et al 2008, Wei et al 2012, Meng et al 2013, Schmidt et al 2014, Lan et al 2015, endometriosis compared to non-endometriosis , Allegra et al 2014, Barcelos et al 2015 and diminished ovarian reserve compared to normal ovarian reserve (Greenseid et al 2011, Jindal et al 2012, May-Panloup et al 2012) have all been shown to alter gene expression. In fact, PCOS patients with or without insulin resistance were shown to have DRGE compared to non-PCOS normal control patients (Kaur et al 2012).…”