Effect of bisphenol A on alterations of ICAM-1 and HLA-G genes expression and DNA methylation profiles in cumulus cells of infertile women with poor response to ovarian stimulation

Abstract

This study aimed to investigate the relationship between follicular fluid Bisphenol A (BPA) concentrations with alterations of ICAM-1 and HLA-G genes and proteins expression as well as methylation profiles in the cumulus cells of poor ovarian response (POR) women based on their healthy lifestyle habit. Eighty women under the age of 35 were divided into two groups: 1—POR without using plastic containers (n = 40) and 2—POR with using plastic containers (n = 40). The ICAM-1 and HLA-G genes and protein expressions were examined by the quantitative PCR and western blotting technique. The methylation pattern was investigated by the methylation-specific PCR. Total BPA in follicular fluid was measured with high-performance liquid chromatography technique and the detection limit was 1.14 ng/ml. ICAM-1 and HLA-G genes were differentially expressed between the two groups studied. ICAM-1, HLA-G genes, and protein expressions in group 1 were up-regulated compared to the second group (P < 0.05). While DNA methylation status in group 1 were decreased compared to the other group (P < 0.05). The concentration of BPA in the follicular fluid of group 1 was lower compared to the second group (P < 0.05). The oocyte quality and clinical pregnancy ratio showed significantly higher in group 1 than in the other ones (P < 0.05). The alteration of ICAM-1 and HLA-G gene expressions in POR women is probably related to BPA concentration. As a result Lifestyle habits may also affect the methylation pattern and protein levels in the cumulus cells of POR women. Additionally, lifestyle habits may be considered as a marker for ovulation, oocyte maturation, preimplantation, and clinical pregnancy process.

Bisphenol-A and Female Fertility: An Update of Existing Epidemiological Studies

“…The researchers also noted that BPA is negatively associated with anti-Müllerian hormone (AMH) and day-3 FSH, but no statistical significance was found [ 27 ]. Two recent studies confirmed the aforementioned data [ 47 , 50 ]. Czubacka et al, in particular, found a negative association of high BPA levels with AFC and AMH [ 47 ].…”

“…Overall, seven studies have investigated the association between serum or urine BPA concentrations and various IVF outcomes [ 23 , 35 , 41 , 45 , 49 , 50 , 51 ]. Most of them reported the absence of a statistically significant association between high BPA concentrations in various human fluids and IVF outcome measures, namely fertilization, clinical pregnancy, and live birth rates [ 23 , 35 , 41 , 51 ].…”

“…However, Nazli Yenigul et al found a lower clinical-pregnancy and live-birth probability, as well as decreased embryo quality, in women undergoing intra-cytoplasmic sperm injection (ICSI) with higher serum and follicular-fluid BPA levels [ 51 ]. Additionally, Aftabsavad et al observed lower clinical pregnancy rates and total embryo and oocyte quality in the group of women with unhealthy lifestyle habits (group 2), among whom the BPA levels also appeared to be significantly higher in comparison to the group with healthy lifestyle habits (group 1) [ 50 ]. Lin et al note a statistically significant association between high urinary BPA levels and decreased embryo implantation, oocyte retrieval and maturation rates [ 49 ].…”

The Function of Cumulus Cells in Oocyte Growth and Maturation and in Subsequent Ovulation and Fertilization

“…Human leukocyte antigen-G (HLA-G) plays a role in the maturation of oocytes and embryo implantation. In human CCs, it was found that a low expression of HLA-G was associated with a poor quality of oocytes and poor fertilization and reduced the development of embryos [ 82 ]. Before fertilization, the exposure of COCs to hydrogen peroxide reduced the rates of cleavage, but it did not result in the death of CCs or oocytes.…”

The Effect of Bisphenol A on the IVF Outcomes Depending on the Polymorphism of the Detoxification System Genes

“…The widespread use of bisphenol A in the food industry is of concern to the scientific community, as this substance can enter the human body. Population studies show that bisphenol A is detected in 95-100% of healthy volunteers [1,2].…”