Researchers in the US have bioengineered an artificial ovary that makes sex hormones in the same proportions as a healthy one. They report that in the lab setting at least, the bioengineered ovary shows sustained released of sex hormones estrogen and progesterone, and suggest it may provide a more natural option for women than hormone replacement therapy.

Ovaries produce eggs and also secrete sex hormones that are important for women’s bone and heart health.

Women who are post-menopausal or whose ovaries are damaged or have been removed, don’t produce sex hormones, which can lead to undesirable effects ranging from hot flashes and vaginal dryness to infertility. There is also an increased risk of osteoporosis and heart disease.

But while drug-based hormone replacement therapy (HRT) can help, it is often not recommended for long-term use due to the increased risk of heart disease and breast cancer.

Reporting in the March issue of Biomaterials, Emmanuel Opara at Wake Forest University, North Carolina, and colleagues, describe how using tissue from rats, they made a bioartificial ovary by placing two hormone-producing ovary cells in an algal capsule to simulate the natural follicular environment, and then stimulated it using pituitary gland hormones.

The capsule has a membrane that is thin enough to allow oxygen and nutrients to enter.

Keeping the ovary cells in a capsule should stop the patient rejecting the artificial ovary, and allow functional ovarian tissue from donors to be used to engineer bioartificial ovaries for women whose ovaries aren’t functioning.

For the study, the team isolated two types of endocrine cell (theca and granulosa) from the ovaries of 21-day-old rats and then evaluated three different ways of encapsulating them.

One way of encapsulating them, which they describe as “multilayer alginate microcapsules” was designed to closely mimic the natural ovary, which contains layers of cells in a three-dimensional shape. The other two encapsulation schemes had two-dimensional designs and were used as controls.

The team then assessed the function and performance of the three capsule systems in the lab by exposing them to two hormones released by the pituitary gland: follicle-stimulating hormone (FSH) and luteinizing hormone (LH). These hormones stimulate the ovaries to produce sex hormones.

All three capsule schemes produced progesterone and estrogen on stimulation, but the multilayer 3D scheme secreted 10 times more estrogen than the other two schemes. Also, over a 30-day period, estrogen production gradually decreased in all but the multilayer 3D scheme.

The multilayer 3D scheme also secreted inhibin and activin, two hormones that interact with the pituitary and hypothalamus and are important for regulating the production of female sex hormones.

Opara says they saw the cells in the multilayer capsules functioning in a similar way to the rats’ natural ovaries.

“The secretion of inhibin and activin … suggests that these structures could potentially function as an artificial ovary by synchronizing with the body’s innate control system,” says Opara.

The researchers see this ability to allow the body’s own feedback mechanisms to control the release of ovarian hormones as another potential advantage of the bioartificial ovary over drug-based HRT.

Opara says they are already working on the next step, which is to evaluate the bioartificial ovary approach in animals.

Funds from the National Institutes of Health helped finance the study.

In a study reported recently in PLOS ONE, scientists describe how using nanoparticles as “Trojan horses”, they may have found a way to deliver chemo drugs that protects the fertility of women having cancer treatment.

Written by Catharine Paddock PhD