Global Transcriptional Profiling of Granulosa Cells from Polycystic Ovary Syndrome Patients: Comparative Analyses of Patients with or without History of Ovarian Hyperstimulation Syndrome Reveals Distinct Biomarkers and Pathways

Abstract

Ovarian hyperstimulation syndrome (OHSS) is often a complication of polycystic ovarian syndrome (PCOS), the most frequent disorder of the endocrine system, which affects women in their reproductive years. The etiology of OHSS is multifactorial, though the factors involved are not apparent. In an attempt to unveil the molecular basis of OHSS, we conducted transcriptome analysis of total RNA extracted from granulosa cells from PCOS patients with a history of OHSS (n = 6) and compared them to those with no history of OHSS (n = 18). We identified 59 significantly dysregulated genes (48 down-regulated, 11 up-regulated) in the PCOS with OHSS group compared to the PCOS without OHSS group (p-value < 0.01, fold change >1.5). Functional, pathway and network analyses revealed genes involved in cellular development, inflammatory and immune response, cellular growth and proliferation (including DCN, VIM, LIFR, GRN, IL33, INSR, KLF2, FOXO1, VEGF, RDX, PLCL1, PAPPA, and ZFP36), and significant alterations in the PPAR, IL6, IL10, JAK/STAT and NF-κB signaling pathways. Array findings were validated using quantitative RT-PCR. To the best of our knowledge, this is the largest cohort of Saudi PCOS cases (with or without OHSS) to date that was analyzed using a transcriptomic approach. Our data demonstrate alterations in various gene networks and pathways that may be involved in the pathophysiology of OHSS. Further studies are warranted to confirm the findings.

Human ovarian follicular granulosa cells isolated during ART procedure reflect substantial changes in activation of hormonal signaling pathways, during long-term in vitro conditions

“…Moreover previous studies have reported that insulin signaling, which includes INSR gene is essential for folliculogenesis, granulosa cell differentiation and ovulation and insulin resistance is one of the significant aberrations in polycystic ovarian syndrome (PCOS) [45][46][47].…”

Melatonin Ameliorates Ovarian Hyperstimulation Syndrome (OHSS) through SESN2 Regulated Antiapoptosis

“…Nevertheless, high estradiol levels in the presence of human chorionic gonadotropin (hCG) increase the vascular endothelium permeability, leading to a massive shift of intravascular fluid into the third space. There are also evidences that during the pathogenesis of this iatrogenic complication, large amounts of angiotensin II, vascular endothelial growth factor (VEGF), interleukins (ILs), nitric oxide (NO), tumor necrosis factor-a (TNF-a), and other molecules are excessively produced, causing the overproduction of reactive oxygen species (ROS) which results in oxidant-antioxidant imbalance [ 8 ]. The vascular endothelium is then deteriorated by these imbalanced free radicals that cannot be antagonized by free radical scavengers; consequently, high vascular permeability occurs and finally results in the aggravation of OHSS [ 9 ].…”