ADAMTS1 and HSPG2 mRNA levels in cumulus cells are related to human oocyte quality and controlled ovarian hyperstimulation outcomes

Yerong Ma,Peipei Ren,Yinli Zhang,Songying Zhang,Weijie Yang,Jiamin Jin,Xiaomei Tong,Yongdong Dai,Yibin Pan

doi:10.1007/s10815-019-01659-8

Abstract

PurposeThe study investigated potential correlations between the expression levels of ADAMTS1 and HSPG2 in cumulus cells (CCs) and controlled ovarian hyperstimulation (COH) outcomes.MethodsRT-PCR was used to determine ADAMTS1 and HSPG2 mRNA levels in mice CCs at different timepoints (0, 4, 8, 12, and 16 h) after human chorionic gonadotropin (hCG) injection, and in CCs after RNAi treatment. Women with polycystic ovary syndrome (PCOS) (n = 45) and normal ovulatory controls (n = 103) undergoing IVF/ICSI were recruited. Relative ADAMTS1 and HSPG2 mRNA levels were measured by RT-PCR. Moreover, correlations of ADAMTS1 and HSPG2 levels with COH outcomes were analyzed.ResultsAt different timepoints after hCG treatment, ADAMTS1 mRNA had the highest level at 12 h, whereas HSPG2 showed opposite profiles to ADAMTS1 with the lowest level at 12 h. HSPG2 expression was upregulated after ADAMTS1 RNAi treatment The PCOS group had higher HSPG2 and lower ADAMTS1 expression levels than controls. In normal ovulatory women (control group), a higher expression of ADAMTS1 and lower expression of HSPG2 were associated with more mature oocytes, transplantable embryos, and good quality embryos, whereas higher transplantable embryo rates and good quality embryo rates were obtained only with lower HSPG2 expression. ROC curves showed the co-measurement of ADAMTS1 and HSPG2 had a better predictive power than separate analyses.ConclusionThe dynamic profiles of ADAMTS1 and HSPG2 were inversely correlated in CCs. In PCOS and normal ovulatory patients, higher ADAMTS1 and lower HSPG2 expression levels in CCs were related to better COH outcomes.

Highlights

Ovulation, stimulated by a luteinizing hormone (LH) surge, is a dynamic series of events that includes oocyte meiosis resumption, cumulus expansion, follicle rupture, and cumulus oocyte complex (COC) release
We wished to evaluate the expression timing of ADAMTS1 and HSPG2 during ovulation and conducted experiments in the mouse evaluating the expression of these genes following human chorionic gonadotropin (hCG) injection
Human oocytes were collected at 36 h after the injection of hCG in the controlled ovarian hyperstimulation (COH) cycle, and this timepoint was equivalent to approximately 12 h in mice

Summary

Introduction

Ovulation, stimulated by a luteinizing hormone (LH) surge, is a dynamic series of events that includes oocyte meiosis resumption, cumulus expansion, follicle rupture, and cumulus oocyte complex (COC) release. LH mainly triggers the ERK1/ ERK2 signaling cascade in granulosa cells (GCs) to induce the expression of many genes crucial for ovulation, oocyte meiosis, and extracellular matrix (ECM) remodeling [1]. Many of these ERK1/ERK2-dependent genes, including AREG, ADAMTS1, and CITED2, in GCs were associated with oocyte quality and IVF outcomes [2,3,4,5,6,7]. ECM remodeling occurs throughout the whole ovulation process.

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