Associations between PON1 enzyme activities in human ovarian follicular fluid and serum specimens

Abstract

The importance of high-density lipoprotein (HDL) particle components to reproduction is increasingly recognized, including the constituent paraoxonase 1 (PON1). However, the reliability characteristics of PON1 enzymes in ovarian follicular fluid (FF) as biomarkers for clinical and epidemiologic studies have not been described. Therefore, we characterized PON1 enzymes in FF and serum and assessed the impact of the PON1 Q192R polymorphism on associations between enzyme activities in two compartments. We also evaluated associations between HDL particle size and enzyme activities. We collected FF and serum from 171 women undergoing in vitro fertilization. PON1 activities were measured as paraoxonase and arylesterase activities, and HDL particle size was determined by 1H NMR spectrometry. Reliability indices for PON1 activities were characterized and we evaluated HDL particle sizes as predictors of PON1 enzyme activities. We found that PON1 enzyme activities were correlated between compartments, but higher in serum than in FF. For FF, the index of individuality (II) was low and the coefficient of variation (CV%) was high for paraoxonase activity overall (0.12 and 11.51%, respectively). However, IIs increased (0.33–1.30) and CV%s decreased (5.58%-8.52%) when stratified by PON1 Q192R phenotype. The intraclass correlation coefficient (ICC) for FF paraoxonase activity was high overall (0.89) but decreased when stratified by PON1 Q192R phenotype (0.43–0.75). We found similar, although more modest, patterns for FF arylesterase activity. For enzyme activities in serum, ICCs were close to 1.00 across all phenotypes. Additionally, different HDL particle sizes predicted PON1 enzyme activities according to PON1 Q192R phenotype. Overall, stratification by PON1 Q192R phenotype improved the reliability characteristics of FF PON1 enzymes as biomarkers for use in clinical investigations but diminished usefulness for epidemiologic studies. Thus, we recommend stratification by PON1 Q192R phenotype for clinical but not epidemiologic investigations, when employing FF PON1 enzyme activity biomarkers.

Toxic elements in follicular fluid adversely influence the likelihood of pregnancy and live birth in women undergoing IVF

“…Similar to previous reports ( Li et al , 2006 ; Kim et al , 2017 ), we found more PON1 Q192R R+ phenotypes in Asian than in other women as described in Supplementary Table SVII , and higher PON1p activity among R+ women compared to QQ women ( Humbert et al , 1993 ), shown in Supplementary Table SVIII . Greater PON1p activity was associated with lower blood Hg and Pb in prior work ( Ginsberg et al , 2014 ; Li et al , 2006 ), with a more pronounced association among PON Q192R RR homozygotes ( Li et al , 2006 ).…”

Reproductive Health Risks Associated with Occupational and Environmental Exposure to Pesticides

“…Furthermore, PON1 polymorphisms are also differently distributed between ethnic groups. Among Caucasians, a PON1 192R-allele frequency of approximately 25% has been reported, but in other populations the R-allele frequency was considerably higher (40-70%), particularly among South American and African populations, as well as being very high in Asian populations [140][141][142]. Thus, susceptibility to the adverse health effects of organophosphate insecticides is likely to be considerably different between different populations.…”

HDL functionality in follicular fluid in normal-weight and obese women undergoing assisted reproductive treatment

“…The presence of HDL in the FF is influenced by the follicular basal lamina and by perifollicular vascularity [18]. Previous studies have shown that HDL contribute to the intra-follicular homeostasis of cholesterol and have a role in embryo development [18][19][20]. It has been also proposed that antioxidant molecules in FF could play a role in maintaining the control of the redox balance of follicular fluid which is essential for a correct oocyte maturation.…”