Genome-wide screening differential long non-coding RNAs expression
profiles discloses its roles involved in OHSS development
Received: 3 February 2018 /Accepted: 25 April 2018
Springer Science+Business Media, LLC, part of Springer Nature 2018
Objective To screen differentially expressed lncRNAs involved in OHSS. OHSS is defined as ovarian hyperstimulation syn-
drome. It is characterized as enlarged ovary and increased vascular permeability.
Design Case-control study.
Setting University-affiliated hospital.
Patient(s) Patients with OHSS high risk (n = 30) and low risk (n = 30) were included in this study.
Main outcome measure(s) LncRNAs from women with OHSS high risk and low risk were used for high-throughput sequencing
profiling. The eight most differentially expressed lncRNAs in granulosa cells were validated by semi-quantitative reverse
transcription-polymerase chain reaction analysis.
Result(s) A total of 23,815 lncRNAs were detected and 482 were differentially expressed (fold-change ≥2; p <0.05,FDRvalue
< 0.001), of which 205 were upregulated and 277 were downregulated. Lnc-SEC16B.1-6, lnc-SNURF-13, lnc-LGR6-6, and lnc-
H2AFY2-2 were up-regulated, while lnc-BRD2-2, lnc-HSPA6-2, and lnc-CLIC6-5 were downregulated significantly in granu-
losa cells. These results were confirmed by qRT-PCR. KEGG pathways and Gene Ontology enrichment analysis revealed that
several biological processes were significantly associated. Meanwhile, the lncRNA/miRNA interaction network was established
according to ceRNA network model.
Conclusion(s) Comprehensive expression screening identified eight novel lncRNAs associated with risk factors of OHSS pro-
cess. Although it is unclear how these altered lncRNAs regulate the process of OHSS, our findings suggest these lncRNAs may
be novel players in OHSS development.
Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic
and serious complication of controlled ovarian stimulation
among reproductive age women in assisted reproductive
technology (ART) [1, 2]. The symptoms of OHSS contains
series of clinical features including ovarian enlargement, as-
cites, high vascular permeability, high level of 17 β-estradiol
(E2), and thrombotic complications [3, 4].The severity of
OHSS can be classified as mild, moderate, and severe ac-
cording to the assessment of clinical manifestations, and
mild OHSS can occur in up to 32% of IVF cycles .
Especially, in in vitro fertilization cycles, the incidence of
moderate to severe OHSS can be up to 10% under the effect
of exogenous gonadotropin stimulation . Vascular perme-
ability has been considered as the main cause to OHSS and
vascular endothelium growth factor (VEGF) should take the
responsibility to vascular permeability [7, 8]. As an inflam-
matory factor, VEGF can induce local capillaries leaky via
binding to its receptor VEGF receptor 2 (VEGFR2) in endo-
thelial cell membrane [9, 10]. Despite abundant achievement
has been obtained of OHSS, the pathogenesis and regulatory
mechanisms of OHSS are still dismal.
Electronic supplementary material The online version of this article
(https://doi.org/10.1007/s10815-018-1199-0) contains supplementary
material, which is available to authorized users.
* Qingxue Zhang
Department of Gynecology and Obstetrics, Sun Yat-Sen Memorial
Hospital, Guangzhou, China
Department of Gynecology and Obstetrics, The third Affiliated
Hospital, Sun Yat-Sen University, Guangzhou, China
Journal of Assisted Reproduction and Genetics