The presence of antibodies to oxidative modified proteins in serum from polycystic ovary syndrome patients

Abstract

Polycystic ovary syndrome (PCOS) affects 5-10% of women of reproductive age. Free radicals, as a product of oxidative stress, impair cells and tissue properties related to human fertility. These free radicals, together with the oxidized molecules, may have a cytotoxic or deleterious effects on sperm and oocytes, on early embryo development or on the endometrium. Aldehyde-modified proteins are highly immunogenic and circulating autoantibodies to new epitopes, such as malondialdehyde (MDA), may affect the reproductive system. Autoantibodies or elevated reactive oxygen species (ROS) in serum are often associated with inflammatory response. The purpose of this work is to investigate whether PCOS women show increased levels of oxidized proteins (protein-MDA) and anti-endometrial antibodies (AEA) in their sera, compared with control patients, and to determine whether AEA specificity is related to oxidized protein derivatives. Sera from 31 women [10 patients with PCOS (PCOS group) and 21 women with male factor of infertility (control group)] were chosen from patients attending for infertility. Anti-endometrial antibodies were determined by enzyme-linked immunosorbent assay (ELISA) with an endometrial cell line (RL-95). Antibodies against MDA modified human serum albumin (HSA-MDA) were also determined by ELISA. Oxidized proteins (protein-MDA) in serum were determined by a colorimetric assay. Patients with PCOS have significantly higher levels of AEA and anti-HSA-MDA, as well as oxidized proteins (protein-MDA) in serum than control patients. For the first time, we describe an autoimmune response in PCOS patients, in terms of AEA. The evidence of protein-MDA in the serum of these patients, together with the increased antibody reactivity to MDA-modified proteins (HSA-MDA) in vitro, supports the conclusion that oxidative stress may be one of the important causes for abnormal endometrial environment with poor embryo receptivity in PCOS patients.

Fig. 1

Anti-endometrial (AEA) and anti-ephitelial (AepA) antibodies in the serum of patients. Results were expressed as absorbance units (A) at 620 nm. Symbols refer to mean values and bars to s.e.m. **P < 0·01.

Fig. 2

Malondialdehyde (MDA) levels bound to proteins (protein–MDA) in the serum of patients. Symbols refer to mean values and bars to s.e.m. **P < 0·01.

Fig. 3

Anti-human serum albumin (HSA) and anti-HSA-malondialdehyde (MDA) antibodies in serum of polycystic ovary syndrome patients. Results were expressed as absorbance units (A) at 620 nm; n.s. = not significant. *P < 0·05.