Handy, April M.2025-01-032025-01-032003-09http://hdl.handle.net/11603/37129Endometriosis, defined as the presence and proliferation of endometrial tissue outside the uterus, affects up to 20% of women of reproductive age and can cause severe pelvic pain and infertility. It is well known that endometrial tissue proliferates under the influence of estrogen and that inflammation is most severe when circulating levels are high (late follicular phase of the menstrual cycle). The mechanism(s) leading to the implantation and proliferation of ectopic endometrial tissue in some women, while re-absorption occurs in others, is not known. Current therapy for the disease focuses on controlling the production of estradiol, and in some cases, inhibiting it completely along with reducing the ectopic tissue with periodic abdominal surgery. Understanding the mechanism(s) underlying the initiation and progression of endometriosis may allow for the development of less invasive, targeted therapies. Hypothetically, the incidence and/or progression of proliferative diseases, such as endometriosis, could be reduced if the overall rate of cellular proliferation could be controlled. Calorie restriction (CR), a nutritional intervention that extends lifespan and retards age-related disease in a variety of short-lived species, has been shown to reduce proliferation in lymphocytes as well as liver and mammary tissue. Calorie restriction has also been shown to reduce both spontaneous and induced forms of cancer in rodents. A preliminary report from the Institute on Aging (NIA) longitudinal study of CR in nonhuman primates showed a reduced incidence of naturally occurring endometriosis in CR vs. ad libitum (AL) female rhesus monkeys (22.6% and 11.1%, respectively). Assessment of the entire colony will not be available for many years due to the longer than thirty-year lifespan of rhesus monkeys. Therefore, the purpose of this study was to begin to examine the possible protective function(s) of CR against proliferation of extrauterine endometrial tissue in an established, short-lived model of rat endometriosis. In this study, forty female Fisher 344 rats were divided into two groups: ad-libitum fed (AL) and calorie restricted (CR) that received 40% fewer calories. Half of the animals in each diet group underwent abdominal surgery during which one uterine horn was removed, divided, and autotransplanted onto alternating descending arterial cascades in the mesentery surrounding the small intestine. Sham-operated animals in both diet groups served as controls. The implants were allowed to remain for five to six weeks and were compared for growth during a second abdominal surgery. Body weight was significantly lower in the CR group as was the weight of the remaining intact uterine horn at the time of the second surgery. The percentage of endometrial implants surviving at five to six weeks was not significantly different between the two diet groups. The overall growth of implanted tissue was higher in the CR group. This preliminary investigation produced no clear evidence that proliferation of uterine tissue is slowed by the proposed dietary intervention. Although the results gathered in this study do not confirm our original hypothesis, there are other aspects of endometriosis, primarily the attachment process, which remain to be explored.55 pagesen-USText