Human follicular fluid proteome reveals association between overweight status and oocyte maturation abnormality

Xin Liu,Juan Liu,Ning Li,Fujun Liu,Yanwei Wang,Wenting Wang,Wendi Zhang,Peng Zhu,Xiaofang Shen,Yanhua Wang,Chengli Zhang,Jiahui Wang

doi:10.1186/s12014-020-09286-7

Abstract

BackgroundHuman follicular fluid (HFF), which is composed by essential proteins required for the follicle development, provides an important microenvironment for oocyte maturation. Recently, overweight status has been considered as a detrimental impact factor on oocyte maturation, but whether HFF proteome could provide protein markers for assessing overweight-based oocyte maturation deficiency is still unknown.MethodsTo reveal the HFF-based molecular characteristics associated with abnormal oocyte maturation, an iTRAQ-based comparative proteomic analysis was performed to investigate different HFF protein expression profiles from normal weight women and overweight status women.ResultsTwo hundred HFF proteins were quantified in our data, of which 43% have not been overlapped by two previous publications. Compared with the HFF proteins of normal weight women, 22 up-regulated HFF proteins and 21 down-regulated HFF proteins were found in the overweight status women. PANTHER database showed these altered HFF proteins participated in development, metabolism, immunity, and coagulation, and STRING database demonstrated their complicated interaction networks. The confidence of proteomic outcome was verified by Western blot analysis of WAP four-disulfide core domain protein 2 (WFDC2), lactotransferrin (LTF), prostate-specific antigen (KLK3), fibronectin (FN1), and glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Further, ELISA assay indicated WFDC2 might be a potentially useful candidate HFF marker for the diagnosis of oocyte maturation arrest caused by overweight status.ConclusionsOur work provided a new complementary high-confidence HFF dataset involved in oocyte maturation, and these altered HFF proteins might have clinical relevance and diagnostic and prognostic value for abnormal oocyte maturation in overweight status women.

Highlights

Infertility remains a rising worldwide problem, characterized by the failure to achieving clinical pregnancy after 12 months of regular attempts of natural fertilization
200 Human follicular fluid (HFF) proteins were identified and quantified using the ProteinPilotTM software to search against the reviewed Swiss-Prot human database (20,316 sequences, 2018_02 released) with a high confidence (FDR < 0.01) (Additional file 1: Table S1)
Annotations of altered proteins identified in HFF from the overweight status women compared with the normal weight women

Summary

Introduction

Infertility remains a rising worldwide problem, characterized by the failure to achieving clinical pregnancy after 12 months of regular attempts of natural fertilization. Overweight status has been considered to have a detrimental impact on female reproductive health, which involves disorder of the ‘hypothalamic-pituitary-ovarian axis’. These dysfunctional female gonads negatively influence oocyte development and hormone secretion, leading to ovulatory dysfunction and female infertility [5, 6]. Human follicular fluid (HFF), which is composed by essential proteins required for the follicle development, provides an important microenvironment for oocyte maturation. Overweight status has been considered as a detrimental impact factor on oocyte maturation, but whether HFF proteome could provide protein markers for assessing overweight-based oocyte maturation deficiency is still unknown

Methods

Results

Discussion

Conclusion