Hysterectomy Uniquely Impacts Spatial Memory in a Rat Model: A Role for the Nonpregnant Uterus in Cognitive Processes

Stephanie V. Koebele, Justin M. Palmer, Bryanna Hadder, Ryan Melikian, Carly Fox, Isabel M. Strouse, Dale Denardo, Christina George, Emily Daunis, Adrianna Nimer, Loretta P. Mayer, Cheryl A. Dyer, Heather Bimonte-Nelson

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Abstract

Approximately one-third of women experience hysterectomy, or the surgical removal of the uterus, by 60 years of age, with most surgeries occurring prior to the onset of natural menopause. The ovaries are retained in about half of these surgeries, whereas for the other half hysterectomy occurs concurrently with oophorectomy. The dogma is that the nonpregnant uterus is dormant. There have been no preclinical assessments of surgical variations in menopause, including hysterectomy, with and without ovarian conservation, on potential endocrine and cognitive changes. We present a novel rat model of hysterectomy alongside sham, ovariectomy (Ovx), and Ovx-hysterectomy groups to assess effects of surgical menopause variations. Rats without ovaries learned the working memory domain of a complex cognitive task faster than did those with ovaries. Moreover, uterus removal alone had a unique detrimental impact on the ability to handle a high-demand working memory load. The addition of Ovx, that is, Ovx-hysterectomy, prevented this hysterectomy-induced memory deficit. Performance did not differ amongst groups in reference memory-only tasks, suggesting that the working memory domain is particularly sensitive to variations in surgical menopause. Following uterus removal, ovarian histology and estrous cycle monitoring demonstrated that ovaries continued to function, and serum assays indicated altered ovarian hormone and gonadotropin profiles by 2 months after surgery. These results underscore the critical need to further study the contribution of the uterus to the female phenotype, including effects of hysterectomy with and without ovarian conservation, on the trajectory of brain and endocrine aging to decipher the impact of common variations in gynecological surgery in women. Moreover, findings demonstrate that the nonpregnant uterus is not dormant, and indicate that there is an ovarian-uterus-brain system that becomes interrupted when the reproductive tract has been disrupted, leading to alterations in brain functioning.

Original languageEnglish (US)
Pages (from-to)1-19
Number of pages19
JournalEndocrinology
Volume160
Issue number1
DOIs
StatePublished - Jan 1 2019

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ASJC Scopus subject areas

  • Endocrinology

Cite this

Koebele, S. V., Palmer, J. M., Hadder, B., Melikian, R., Fox, C., Strouse, I. M., Denardo, D., George, C., Daunis, E., Nimer, A., Mayer, L. P., Dyer, C. A., & Bimonte-Nelson, H. (2019). Hysterectomy Uniquely Impacts Spatial Memory in a Rat Model: A Role for the Nonpregnant Uterus in Cognitive Processes. Endocrinology, 160(1), 1-19. https://doi.org/10.1210/en.2018-00709