Bisphenols as recent endocrine disruptor endangering human reproduction
Project no. NV18-01-00544
Category PROJEKTY AZV ČR / Czech Health Research Council PROJECTS
Human population is exposed to a broad spectrum of endocrine disruptors. Bisphenol A (BPA) are one of the group that is widely used in items of daily needs. BPA has previously been shown to negatively affecting human reproduction and usage of assisted reproductive technology (ART). However, substitution of BPA by alternative BPs brought serious problems, such as unproven harmlessness of other BPs (BPS, BPF, BPAF) and possible interactions of individual BPs in organism. Moreover, the molecular mechanism of BPs negative effect and real impact on human reproductive health remains unclear. We hypothesize that human population is exposed to BPs, negatively affecting human reproduction. The aim of the project is a) to describe a relationship of BPs‘ level in human seminal plasma/follicular fluid and ART outcomes and b) to describe mechanism of BPs‘ action experimentally, using models (i.e. mouse, pig and human follicular cells). The estimation of BPs‘ risk for human reproductive health and description of molecular mechanism will become a background for the solution of the BPs‘ problem.
1) The biomonitoring of human population; a) the detection and quantification of BPs in seminal plasma and follicular fluids of patients undergoing the ART, b) the correlation analysis of BPs‘ content in the fluids with sperm quality and outputs of ART, c) the survey of the influence of anamnesis, profession and life style on BPs‘ exposure based on evaluation of questionnaires. 2) The study of biological models for evaluation of individual BPs‘ (with emphasis on bisphenol detected in Task 1, including a combination of BPs) on molecular mechanism. Human follicular cells will be included onto the index of the biological models for BPs study; a) to evaluate the effect of in vivo BP exposure on testis histology and sperm quality of mice, b) to evaluate the effect of in vivo BP exposure on quality of ovaries and oocytes of mice, c) to evaluate the effect of BP on embryonic development of mice, d) to evaluate the effect of BP on time course of pig oocyte maturation and assessment of the expansion of cumulus cells, e) characterization of BPs‘ target systems (on mRNA and protein level) in matured oocytes of mice and pigs, f) to evaluate the BPs effect on viability of human follicular cells.