Transferrin Insufficiency and Iron Overload in Follicular Fluid Contribute to Oocyte Dysmaturity in Infertile Women With Advanced Endometriosis.

Anji Li,Zailong Cai,Yanping Kuang,Jie Zhang,Chaoqin Yu,Zhexin Ni

doi:10.3389/fendo.2020.00391

Abstract

Purpose: To screen out specific protein with different concentration in follicular fluid from advanced endometriosis and determine its direct effect on mouse oocytes matured in vitro.Methods: FF samples were obtained from 25 patients (EMS group, n = 15; control group, n = 10) to screen the differential proteins by using iTRAQ Labeling and 2D LC-MS. Transferrin (TRF) in was found significantly decreased in EMS group, which was verified using ELISA in enlarged FF samples (EMS group, n = 31; control group, n = 27). The contents of ferric ion in FFs were detected by ELISA and TRF saturations were calculated in two groups. Germinal vesicle (GV) oocytes of mouse were maturated in vitro interfered with the FFs in five groups, whose concentrations of TRF were modulated, and maturation in vitro rates were compared among groups.Results: The reduced concentration of TRF with three analogs and increased concentration of ferric ion were found in the FF of the EMS group (p < 0.05). The numerical values of TSAT was 54.8% in EMS group, indicating iron overload in the FF. The EMS-FF showed significantly decreased maturation in vitro rate (p < 0.05) of mouse oocytes, which was improved with the supplementation of TRF, compared with the control-FF. The effect was blocked by the TRF antibody (p < 0.05).Conclusions: Being aware of the relatively small sample size, our results possibly suggest that TRF insufficiency and iron overload in FF from advanced EMS contribute to oocytes dysmaturity, which may be a cause of EMS-related infertility.

Highlights

Endometriosis (EMS) is an estrogen (E2)-dependent disease wherein the endometrial stromal and glandular epithelial cells are externally implanted from the uterus
The decreased number of mature oocytes retrieved in women with endometriosis compared to women with other causes of infertility was reported in prospective case-control studies [8,9,10] and meta-analysis [11], which indicated dysmaturity of oocytes of patients with EMS
Controlled ovarian hyperstimulation to patients was performed by 150–225 IU/day of human menopausal gonadotropin (Anhui Fengyuan Pharmaceutical Co., China) and 4 or 10 mg/day of medroxyprogesterone acetate (MPA) (Beijing ZhongXin Pharmaceutical, China) from menstrual cycle day 3, according to the observed follicular growth by ultrasound and blood test

Summary

Introduction

Endometriosis (EMS) is an estrogen (E2)-dependent disease wherein the endometrial stromal and glandular epithelial cells are externally implanted from the uterus. The changes in the reproductive tract anatomy, impaired follicular development, ovulation dysfunction, embryo implantation difficulties, and other factors may cause infertility in patients with EMS [3]. Patients with EMS have less oocytes retrieved and higher rate of cycle cancellation than EMS-free controls in oocytes retrieval cycles [5,6,7]. The number of oocytes retrieved directly reflects ovarian response and is one of the best clinical markers of oocyte quality, which indicates their ability to complete maturation and undergo successful fertilization [8]. The decreased number of mature oocytes retrieved in women with endometriosis compared to women with other causes of infertility was reported in prospective case-control studies [8,9,10] and meta-analysis [11], which indicated dysmaturity of oocytes of patients with EMS. The mechanism of dysmaturity of oocytes in endometriosis remain largely unknown

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