Ovarian Cell Response to Phthalates and Non-Phthalate Alternatives ‡ Cassius Long * Project Mentor(s): April K. Binder, PhD Polycystic ovarian syndrome (PCOS) is an endocrine disorder characterized by reduced ovarian ovulation. Some studies theorize that PCOS may be caused by environmental factors, such as chemical irritants. Phthalates are synthetic chemicals that are added to consumer products to increase malleability. Phthalates can easily be released from their products due to weak chemical bonding, and leak into the environment. Previous research on the phthalates DEHP and MEHP have shown that these chemicals are endocrine disruptors, causing infertility in humans and interrupting hormone binding. Due to this observed toxicity, non-phthalate alternatives, including ATBC, were manufactured. However, studies have found these alternatives caused a reduction in follicular growth in mouse ovaries. This study seeks to determine how excess exposure to testosterone impacts human ovarian cell proliferation when also exposed to DEHP or MEHP, or the phthalate alternative ATBC. Testosterone exposure can be used to model PCOS in vitro; herein we used pre-exposure of DHT in human BG1 ovarian cells to simulate a PCOS cellular response to these chemicals. Treatment with either DEHP, MEHP, or the non-phthalate ATBC alone significantly reduced BG1 cell proliferation. We found treatment with DHT and DEHP, MEHP, or ATBC caused a twofold decrease in cell proliferation. These results indicate that DHT is impacting how the ovarian cells are responding to the phthalates and their alternatives. Further understanding of the mechanisms activated by DEHP/MEHP and the non-phthalate ATBC will help expand our understanding of how excess exposure of testosterone is impacting ovarian cell response in patients with PCOS. Commercial pollutants have accumulated global concern within their impact on suspected dysregulation of environmental and organismal health systems. Within this project, Girardia tigrina, also known as “brown planaria”, are used to observe the possible negative effects of per- and polyfluoroalkyl substances (PFAS) and respective derivatives on pluripotent stem cell proliferation and differentiation. Planarian, the flat worm species, have genetic conservation across zebra fish and humans (~13.8%); with an emphasis on genetic orthologs within pluripotent stem cell pathways. Given the asexual nature of planaria, reproduction of the species heavily relies on a self-ripping process known as “fission”, where injury will induce stem cell proliferation characterized by blastema formation. Blastema growth is recognized by its transparent-milky-white pigment with indistinct phenotypic features that would typically indicate fully differentiated cells, such as photosensors. To simulate these effects within a lab setting, surgical removal of the head and tail will be performed to induce blastema formation after injury. This growth will be recorded up until cell differentiation, which is indicated via visibility of formed photoreceptors. Daily imaging of the proliferating period via blastema growth acts as a measurement of stem cell proliferation within toxicity studies such as PFAS chemical exposure. The fast and effective regenerative nature of planaria makes Girardia tigrine an ideal species for conducting qualitative and quantitative research regarding how PFAS chemicals can have an observable effect on pluripotent stem cell proliferation and later differentiation. Presentation Type: Poster Presentation (May 21, 9:30am–3:00pm) Keywords : Planaria, Pluripotent, Regeneration SOURCE Form ID: 192 Presentation Type: Oral Presentation (May 20, 9:30am–5:00pm) Keywords: Endocrinology, Phthalates, PCOS, Ovarian Cell SOURCE Form ID: 140 Girardia tigrina –An Effective Model for Stem Cell Research Davnia McKnight Project Mentor(s): April Binder, PhD
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