SWATHHM-Based Metabolomics of Follicular Fluid in Patients Shows That Progesterone Adversely Affects Oocyte Quality.

Zhengao Sun,Jifeng Deng,Xingxing Zhang,Jingyan Song,Yi Yang,Aijuan Wang,Xiaoming Wang,Kaiyue Xu,Ying Guo

doi:10.1155/2018/1780391

Abstract

Objective We reveal the relationship between progesterone level in follicular fluid and oocyte quality based on sequential window acquisition of all theoretical fragment-ion spectra (SWATH™), a powerful high-resolution mass spectrometric data independent acquisition technique. Method Follicular fluid samples were collected from 22 subjects (the level of progesterone > 1.5 ng/mL) of progesterone group, as well as from 22 subjects (the level of progesterone < 1.5 ng/mL) of control group, and analyzed using UPLC-Q-TOF. All methods were performed in accordance with ISO 9001:2008. Novel SWATH acquisition mode on an ultra-high performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (with resolving power 20,000–40,000) was investigated for the analysis of human follicular fluid. The principal component variable grouping detects intersample variable correlation and groups variables with similar profiles which simplifies interpretation and highlights related ions and fragments. It can also extract product ion spectra from the data collected by fragmenting a wide precursor ion window. Results Follicular fluid from the two groups differed with respect to five metabolites. Follicular fluid from the progesterone group contained elevated levels of 8-hydroxyguanosine and 4-hydroxynonenal and reduced levels of ATP, estradiol, and L-carnitine. The increased progesterone level on the day of HCG injection could negatively impact oocyte quality, thus reducing the pregnancy rate of IVF patients.

Highlights

At present, in vitro fertilization (IVF) and intracytoplasmic sperm injection are the main treatments available for infertility
Aliquots of 2 μL supernatant were injected into the ultraperformance liquid chromatography tandem Triple TOF 5600 system (AB SCIEX, CA, USA) in random order, to avoid complications caused by artifacts related to injection order and occasional changes in instrumental efficiency
The estradiol levels in the progesterone group were reduced, which suggests that the elevated progesterone levels caused abnormal hormone metabolism and resulted in a decline in oocyte quality

Summary

Introduction

In vitro fertilization (IVF) and intracytoplasmic sperm injection are the main treatments available for infertility. Gonadotropin-releasing hormone can induce the production and maturation of multiple eggs, resulting in an increase in pregnancy rates [2]. Embryo quality and endometrial receptivity may be influenced by the exposure to a high level of steroids in the internal environment, which may affect the outcome of pregnancy [3]. During IVF treatment, the serum level of progesterone commonly increases on the day of human chorionic gonadotropin (HCG) administration [4]. Whether the level of progesterone in the serum on the day of HCG administration affects oocyte quality is a controversial topic [5, 6]. Follicular fluid provides an ideal microenvironment for oocyte development, containing the nutrients required for follicle growth and maturation. The presence of altered metabolic components in follicular fluid has been related to follicle quality and developmental potential

Methods

Results

Discussion

Conclusion