Ovarian-Disrupting Effects and Mechanisms of Per- and Polyfluoroalkyl Substances
Abstract
The per- and polyfluoroalkyl substances (PFAS) are a group of thousands of human-made organic compounds that are highly persistent and widely used in many consumer and industrial products, including food packaging, textiles, cookware coating, and surfactants, etc. Since the 1960s, PFAS have also been frequently used as firefighting foam ingredients in military firefighting practice, training, and equipment testing, which has caused the release of PFAS and contamination of drinking water supplies on and near many military bases across the U.S. PFAS are very stable and persistent to environmental degradation, making them earn the name of Forever Chemicals. After entering the human body, PFAS are rarely metabolized and can stay in the body for many years. PFAS are detectable in the blood of more than 90% of populations in the U.S. and many other countries. So far, research has found that human exposure to PFAS may increase the risks of several adverse health issues, such as liver disease, cancers, metabolic diseases, and endocrine disorders. It has been demonstrated that PFAS can accumulate in women’s ovaries, the female gonad that secretes hormones and release fertilizable eggs to sustain a woman’s menstrual cycle and fertility. Research has also found that exposure to PFAS is positively associated with several women’s reproductive disorders, including early menopause, irregular menstrual cycles, and infertility, suggesting toxic effects of PFAS on the ovary and related reproductive functions. Due to the heavy contamination of PFAS in the drinking water supplies of many military bases, it is very possible that female military Service Members are at a great risk of PFAS-induced reproductive toxicities. In addition, because the absorbed PFAS takes many years to be eliminated from human bodies, the reproductive health of female Veterans is also potentially at risk. In the real world, humans, including female military personnel and Veterans, are exposed to mixtures of PFAS. Thus, the aim of this study is to investigate the toxic effects and mechanisms of PFAS on the ovary and female reproductive outcomes; in addition, we will test the ovarian toxicities of PFAS mixtures. We hypothesize that environmentally relevant exposure to PFAS adversely affects a woman’s ovarian functions to cause adverse female reproductive outcomes such as irregular menstrual cycles and sub- or infertility. We propose three Specific Aims to test this hypothesis. In Aim 1, we will study the ovarian accumulation and toxic effects of PFNA, a widely used long-chain PFAS, and associated adverse female reproductive outcomes using an in vivo mouse model. In Aim 2, we will use both in vivo mouse model and 3D in vitro culture of mouse ovarian tissues and human ovarian cells to study how PFNA interferes with ovarian functions. In Aim 3, we will determine the ovarian toxic effects of certain long- and short-chain PFAS alone and in mixtures. This study is very important and highly relevant to the mission of the CDMRP because we focus on an emerging class of environmental contaminants, PFAS, which had caused heavy environmental contamination in the U.S. and worldwide, including drinking water supplies at and around many military bases across the U.S. This study is closely related to the FY22 TERP Program Goal of Elucidate mechanisms of how toxic exposures result in adverse effects, and also highly related to the Topic Areas of Endocrine disrupting chemicals and PFAS. This study is highly impactful and can benefit the reproductive health of both current female military Service Members and Veterans because (1) the understanding of reproductive toxic effects and mechanisms of long-chain and short-chain PFAS and mixtures will enable us to speed up the development of diagnosis, treatment, and prevention methods to protect the reproductive health of female military service members and Veterans; (2) the research models, methods, experience, and exp
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310809
Entities
People
- Shuo Xiao
Organizations
- Rutgers University
- United States Army