The effects of di (2-ethylhexyl) phthalate (dehp) on lesion development in a mouse model of endometriosis

Endometriosis is a common gynecological disorder affecting 6%–10% of women of reproductive age and 35%–50% of women experiencing chronic pelvic pain and/or infertility. The most widely accepted mechanism of this disease is the entry of endometrial cell aggregates into the peritoneal cavity via the fallopian tubes in a process known as retrograde menstruation. These endometrial fragments attach and invade the peritoneal surfaces, eventually forming lesions. Primates are the only species that naturally develop endometriosis, however due to the expense and difficulty of working with these species, models based in laboratory species have been developed. Using a mouse transplantation model of endometriosis that mimics the progression of the disease in humans, we investigated the effects of di (2-ethylhexyl) phthalate, a known endocrine disruptor, on establishment of endometriotic lesions and neuroinflammation. To accomplish this, we validated the optimal estrogen dose for supplementation and monitored lesion progression over time following transplantation surgery. We then determined if mice with endometriotic lesions show signs of pain or discomfort using a behavioral assay. We also examined whether there is a genetic impact on the incidence and progression of endometriosis in our mouse model by comparing two different strains of mice. Finally, we determined the effects of di (2-ethylhexyl) phthalate (DEHP) on lesion development in our mouse model. Our main findings are that, 1) supplementing ovariectomized mice with 100 ng or 1 µg of 17β-estradiol every 4 days is not sufficient for the long term maintenance of endometriotic lesions. However supplementation with estradiol valerate resulted in a higher incidence of endometriotic lesions containing glands; 2) mice with endometriotic lesions show signs of discomfort or pain in association with induction of endometriosis; 3) the presence of endometriotic lesions resulted in increased numbers of activated microglia in the hippocampus of the brain; 4) C57BL/6 mice are a superior mouse strain for use in a mouse model of endometriosis; and 5) treatment of mice with 30 mg/kg/day or 60 mg/kg/day DEHP resulted in increased incidence and size of lesions and increased cell proliferation in endometriotic lesions. These results show that we have validated a mouse model for endometriosis that can be used to investigate how the presence of these lesions leads to increased neuroinflammation and visceral pain and how exposure to environmental factors such as phthalates may promote establishment and progression of this disease. The findings of these studies are highly relevant to understanding the mechanisms of endometriosis in women.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Animal Sciences

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2018

Author dc:creator

• Lawrence, Catherine Reed

Contributors dc:contributor

• Nowak, Romana A.
• Steelman, Andrew
• Li, Quanxi

• Endometriosis
• DEHP
• Phthalate
• Mouse model
• Brain
• Microglia
• Neuroinflammation

Statement dc:rights

• Copyright 2018 Catherine Lawrence

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/101356

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/101356