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Reporter and Curator: Dr. Sudipta Saha, Ph.D.

During menopause a woman’s ovaries stop working—leading to hot flashes, sleep problems, weight gain, and worse, bone deterioration. Now scientists are exploring whether transplanting lab-made ovaries might stop those symptoms. In one of the first efforts to explore the potential of such a technique, researchers say they used tissue engineering to construct artificial rat ovaries able to supply female hormones like estrogen and progesterone. A research carried out at Wake Forest Baptist Medical Center, suggests a potential alternative to the synthetic hormones millions of women take after reaching middle age. A paper describing the findings was published in Nature Communications.

Women going through menopause, as well as those who have undergone cancer treatment or had their ovaries removed for medical purposes, lose the ability to produce important hormones, including estrogen and progesterone. Lower levels of these hormones can affect a number of different body functions. To counteract unpleasant symptoms, many women turn to combinations of hormone replacement medications—synthetic estrogen and progestin. Pharmacologic hormone replacement therapy (pHRT) with estrogen alone or estrogen and progestogens is known to effectively ameliorate the unpleasant symptoms. But hormone replacement carries an increased risk of heart disease and breast cancer, so it’s not recommended for long-term use. In these circumstances artificial ovaries could be safer and more effective.

Regenerative medicine approaches that use cell-based hormone replacement therapy (cHRT) offer a potential solution to temporal control of hormone delivery and the ability to restore the HPO (Hypothalamo-Pituitary-Ovarian) axis in a way not possible with pHRT. Scientists have previously described an approach to achieve microencapsulation of ovarian cells that results in bioengineered constructs that replicate key structure-function relationships of ovarian follicles as an approach to cHRT. In the present study the scientists have adapted an isogeneic cell-based construct to provide a proof-of-concept for the potential benefits of cHRT.

Tissue or cell encapsulation may offer effective strategies to fabricate ovarian constructs for the purpose of fertility and/or hormone replacement. Approaches using segmental ovarian tissue or whole-follicle implantation (typically with a focus on cryopreservation of the tissue for reproductive purposes) have resulted in detectable hormone levels in the blood after transplantation. Previous studies have also shown that autotransplantation of frozen-thawed ovarian tissue can lead to hormone secretion for over 5 years in humans.

Although these approaches can be used to achieve the dual purpose of fertility and hormone replacement in premenopausal women undergoing premature ovarian failure, they would have limited application in postmenopausal women who only need hormone replacement to manage menopausal symptoms and in whom fertility is not desirable. In full development, the technology described in this research is focused on hormone replacement, would meet the needs of the latter group of women that is the postmenopausal women.

The cell-based system of hormone replacement described in this report offers an attractive alternative to traditional pharmacological approaches and is consistent with current guidelines in the U.S. and Europe recommending the lowest possible doses of hormone for replacement therapy. In the present research sustained stable hormone release over the course of 90 days of study was demonstrated. The study also demonstrated the effective end-organ outcomes in body fat composition, uterine health, and bone health. However, additional studies will be required to determine the sustainability of the hormone secretion of the constructs by measuring hormone levels from implanted constructs for periods longer than 3 months in the rat model.

This study highlights the potential utility of cHRT for the treatment and study of conditions associated with functional loss of the ovaries. Although longer-term studies would be of future interest, the 90-day duration of this rodent model study is consistent with others investigating osteoporosis in an ovariectomy model. However, this study provides a proof-of-concept for cHRT, it suffers the limitation that it is only an isogeneic-based construct implantation. Scientists think that further studies in either allogeneic or xenogeneic settings would be required with the construct design described in this report in the path towards clinical translation given that patients who would receive this type of treatment are unlikely to have sufficient autologous ovarian cells for transplantation.

Researchers from Copenhagen, Denmark, were recently able to isolate viable, early stage follicles in ovarian tissue. They have successfully stripped ovarian tissue from its cancerous cells and used the remaining scaffold to support the growth and survival of human follicles. This “artificial ovary” may help y to help women who have become infertile due to cancer and chemotherapy. But, the research is presently at a very preliminary stage and much research is still required to ensure that cancer cells are not reintroduced during the grafting process.

References:

https://www.technologyreview.com/the-download/609677/will-artificial-ovaries-mean-no-more-menopause/

https://www.nature.com/articles/s41467-017-01851-3

https://www.ncbi.nlm.nih.gov/pubmed/23274068

https://www.ncbi.nlm.nih.gov/pubmed/26210678

https://www.ncbi.nlm.nih.gov/pubmed/21954279

http://www.frontlinegenomics.com/news/24423/artificial-ovaries-hope-to-help-infertile-women-conceive-following-chemotherapy/