A cell/tissue-based hormone replacement therapy for ovarian failure: Demonstration of in vivo functions of ovarian endocrine tissue constructs in ovariectomized (Ovx) rats

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 515-547-Female Reproductive Endocrinology
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-525
Sittadjody Sivanandane*1, Justin M. Saul2, John P. McQuilling1, Sunyoung Joo1, James J. Yoo1, Anthony Atala1 and Emmanuel C. Opara1
1Wake Forest University, Winston-Salem, NC, 2Miami University, Oxford, OH
Introduction: Although hormone replacement therapy (HRT) is able to reverse some of the pathological conditions due to loss of ovarian function, depending on the treatment regiment it may also lead to various complications including cancers and cardiovascular diseases. A cell/tissue-based HRT offers the potential to overcome these complications because of its delivery in response to circulating levels of hormones. To date, however, such a cell-based approach has not been reported. Aim: To design tissue-engineered ovarian endocrine constructs and to test their functions in vivo. Methods: Granulosa cells (GC) and theca cells (TC) isolated from the ovaries of 21-day old Fisher 344 rats were encapsulated in alginate multilayered microcapsules to mimic the structural architecture of native follicles. We made 2 different types of this endocrine construct. In one type we had GC positioned in a central alginate core and TC in an outer alginate layer and the two layers were separated by a semi-permeable membrane made of poly-L-Ornithine (PLO). In the 2nd construct, there was another PLO layer added on top of the alginate layer that contains TC prior to an external alginate coat, a construct suitable for allo- and xenograft models. The 2 types of constructs were implanted in omentum pouches created in Ovx Fisher 344 rats. Control groups included: a) untreated Ovx rats (implanted with blank microcapsules) and b) sham-operated ovary-intact rats. Blood samples were collected weekly from all groups for 90 days, while their body weights were monitored. Plasma levels of 17 β-estradiol (E2), progesterone (P4), follicle-stimulating hormone (FSH) and Luteinizing hormone (LH) were measured by ELISA. After euthanasia, uterine histomorphometries were studied. Results: While the plasma levels of E2 and P4 in Ovx rats implanted with the tissue constructs were significantly higher, the FSH and LH levels were significantly lower compared to untreated Ovx rats throughout the follow up. Similarly, the tissue construct-implanted Ovx rats maintained their body weights and uterine weights comparable to the ovary-intact rats, whereas the untreated Ovx rats had atrophied uterus and increased body weights. Conclusion: Our study demonstrates that tissue-engineered ovarian endocrine units can produce sustained levels of physiologically-relevant sex steroids in vivo, thus showing that the endocrine unit of the ovary can be recapitulated ex vivo.

Nothing to Disclose: SS, JMS, JPM, SJ, JJY, AA, ECO

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: This study was supported, in part, by Jack and Pamela Egan and the National Institutes of Health (award # R01DK080897).