The exquisite hormonal signaling that drives the female reproductive system cannot be modeled in a flat petri dish. Scrambling to address history's long dearth of research in women's health and physiology, scientists have now created the first “organ on a chip” model that functionally re-creates the female menstrual cycle. This 3-D system may help scientists understand some causes of recurrent miscarriages and could fuel new studies into birth control and drug development in other areas. Fertility experts hope they might eventually be able to place a sample of an individual woman's cells in such a model and thereby determine the best treatment.
A team led by Northwestern University obstetrics and gynecology professor Teresa K. Woodruff grew human and mouse cells from several reproductive organs in a network of tiny, interconnected cubes. Tubes, valves and pumps pushed air and fluids through the system, mimicking the body's natural circulation. Cells that would die in a petri dish stayed alive for a standard 28-day reproductive cycle.
The researchers jump-started the system's chemical communications with an injection of pituitary hormone. In response, the cells secreted levels of estrogen and progesterone found in a typical menstrual cycle—including during ovulation—replicating the signaling that occurs among different female reproductive organs. The team was also able to simulate hormone activity that takes place shortly after conception, creating a tool that could yield insight into maintaining a successful pregnancy. The research was described earlier this year in Nature Communications.
The system comprises mouse ovarian cells (which produce the same hormones as human ovaries), along with human cells from the fallopian tube, endometrium and cervix. Human liver cells are also included because the organ breaks down many drugs. The work builds on numerous earlier organ-on-a-chip studies that explored ways to model the human body.
The new system is still far from a perfect stand-in for female anatomy: It lacks both the placenta, which is key to supporting pregnancy, and the inflammatory system. Nor can it address how early toxic exposure may affect reproductive health, says Kevin G. Osteen, a professor of obstetrics and gynecology at the Vanderbilt University School of Medicine, who was not involved in the study. But Woodruff says that her team's work will enable new studies on a wide range of conditions, among them cervical diseases, that cannot be modeled in rodents because of cellular differences.