ENDOCRINE DISRUPTING PROPERTIES OF NANOPLASTICS AND PHTHALATES IN THE FEMALE REPRODUCTIVE SYSTEM

Abstract

The female reproductive system serves as a crucial component for continuation of life on Planet Earth. It is one of the most susceptible systems to disruption by environmental contaminants. The ovary is an endocrine tissue that is responsible for hormonal balance essential for reproduction and development. Many chemicals are endocrine disruptors, agents that cause hormone disruption by mimicking hormone function or blocking hormone signaling. Phthalates are notorious endocrine disrupting chemicals widely used in consumer and industrial products. In this dissertation, phthalate mixtures are studied rather than single phthalates to represent environmental exposure. Nanoplastics are considered emerging endocrine disruptors that may lead to similar outcomes as phthalates. Nanoplastics pose significant risk due to their small size, which enables them to enter living things. Nanoplastics have been detected in human organs and tissue, but the health implications are yet unknown. This dissertation aims to address the knowledge gap of the impact of ubiquitous endocrine disruptors such as nanoplastics and phthalates on the female reproductive system utilizing both in vitro and in vivo rodent experimental models. Understanding toxicological effects on the female reproductive system is crucial to maintain healthy reproductive systems and produce healthy offspring. The female reproductive system and endocrine signaling within it are especially vulnerable to disruption by environmental contaminants. In chapter one, we introduce the ovary and the placenta, and their role in the endocrine system. In chapter two, we introduce well-known endocrine disruptors, bisphenols and phthalates, which have been proven throughout the years to cause adverse female reproductive effects, including infertility and pregnancy complications such as miscarriages and fetal growth restriction. In chapter three, we assess the ovarian impacts of exposure to phthalate mixtures at environmentally relevant doses. Using our in vitro model, phthalates were found to interfere with vital cellular functions such as the cell cycle and can impact ovarian steroid hormone levels, which poses a risk for fertility. In chapter four, we assess the effects of nanoplastics on ovarian follicles. Both polystyrene (PS) and polyethylene (PET) were investigated to observe their effects on hormone levels and cell growth. We measured gene expression and hormone levels and found that exposure causes hormonal disruption and impacts hormone synthesis processes. In chapter five, we tested the hypothesis that nanoplastic exposure can lead to placental disruption by crossing the placenta and accumulating in tissue. The placenta is the sole organ responsible for fetal health and development. Any disruption could pose a risk to fetal health. An in vivo mouse model was utilized to study the effects of nanoplastic exposure. Our findings show that exposure to nanoplastics causes disruption of expression of genes that are essential during pregnancy and disruption of placental morphology. This dissertation demonstrates the hazards that environmental pollutants, particularly nanoplastics and phthalate mixtures, pose for the female reproductive system.