A Search for Safer Plastics: Synthesis and Reproductive Toxicity Evaluation of Novel Bisphenols - Project Summary/Abstract
Accumulating evidence shows that bisphenol A (BPA) affects not only the development and growth of
reproductive tissues, but also disrupts female meiosis. The interference of BPA with the meiotic process leads
to the formation of reproductive cells with an incorrect number of chromosomes, resulting in the inability to
conceive, pregnancy loss, and developmental disabilities in offspring. In recent years, increasing health concerns
led manufacturers to seek BPA alternatives, which has resulted in its replacement with bisphenol F (BPF) and
bisphenol S (BPS), for example, in some consumer products. However, numerous studies have indicated that
currently available bisphenol analogs resemble BPA in their ability to interfere with hormones and cause meiotic
errors. The long-term goal of the proposed collaborative research project is to understand the relationship
between bisphenol structure and meiotic fidelity. To this end, we aim to identify bisphenol analogs that pose low
or no risk to human reproductive health. This objective will be accomplished through two specific aims: (1)
Synthesis of a library of novel, structurally diverse bisphenol analogs via phenolic ring substitutions, which have
shown particular promise in mediating lower toxicity in studies involving tetramethylbisphenol F; and (2)
Identification of BPA analogs that pose low or no risk to meiosis using several C. elegans-based assays. These
assays will include the monitoring of C. elegans brood size, germ-cell apoptosis, embryonic lethality, and the
incidence of males that arise as the result of a meiotic error. Bisphenol candidates posing low or no risk to
meiosis will be further evaluated for their endocrine-disrupting properties using a validated human cell-based
assay. Understanding how the structure of bisphenols affect reproductive health could lead to the replacement
of this ubiquitous reproductive toxin with a safer alternative in consumer products. Furthermore, this innovative
proposal will significantly strengthen the research environment in the Department of Natural Sciences at the
Lawrence Technological University by providing our undergraduate students with the opportunity to participate
in a funded, multidisciplinary project with great societal relevance.
