For the first time, ovulation was filmed from start to finish

New imaging data shows that the follicle expands, contracts and finally releases the egg

A mature egg cell “jumps” approximately 400 times in a woman’s life. It is released into the fallopian tube where it is ready for fertilization by sperm. Researchers led by Melina Schuh, Christopher Thomas and Tabea Lilian Marx from the Max Planck Institute for Multidisciplinary Sciences have now succeeded in visualizing the entire ovulation process in mouse follicles in real time. The new live imaging method developed by the team enables the process to be examined with high spatial and temporal resolution, thereby contributing to new insights in fertility research.

During a woman’s fertile phase, 15 to 30 eggs mature in fluid-filled sacs called follicles per menstrual cycle. As they mature, the eggs are supported by specialized cells in the follicle called cumulus cells. However, only the largest and best developed follicle manages to ovulate. The follicle ruptures and the egg is released into the fallopian tube. If fertilization by a sperm cell is successful within 24 hours of ovulation, the egg reaches the uterus, where it can implant and develop into an embryo. Any remaining mature eggs are broken down by the body.

Ovulation is regulated by a complex interaction of hormones, but the actual process of ovulation is still poorly understood. The ovary is located deep in the body, making experimental access difficult. In addition, ovulation occurs within a very narrow time window and it cannot be predicted which of the two ovaries will release the next follicle.

Ovulation in three phases

The research team has now succeeded in observing the entire ovulation process in isolated ovarian follicles of mice under the microscope with high spatial and temporal resolution. “We can distinguish between three phases,” explains Max Planck Director Melina Schuh, head of the Meiosis department. “The follicle expands, contracts and finally releases the egg.”

The first phase, follicle expansion, is driven by the release of hyaluronic acid. Under the microscope, the researchers monitored how the size and shape of the follicles changed during this phase. “During ovulation, fluid flows into the follicles, causing them to grow significantly,” reports Christopher Thomas, a former researcher in Schuh’s department, now a group leader at the Institut de Biology du Développement in Marseille and co-first author of the study. According to the cell biologist, hyaluronic acid secretion is essential for this growth and for the success of ovulation. When the researchers blocked the production of hyaluronic acid, the follicles expanded less and ovulation did not occur.

Muscle cells that are important for ovulation

In the second phase, follicular contraction, smooth muscle cells in the outer layer of the follicle cause the follicle to contract. When the team inhibited the contraction of these muscle cells, the follicles were unable to contract – again with serious consequences for the egg. “In this case too, ovulation failed,” says Thomas. “When the follicle ruptures, which happens in the third phase, the egg is released and ovulation is complete,” explains Tabea Lilian Marx, also co-first author and doctoral student in the Meiosis department. “The surface of the follicle bulges outward and eventually ruptures, releasing the follicular fluid, cumulus cells, and ultimately the egg,” she explains.

After ovulation, the follicle forms a structure called the corpus luteum, which produces the hormone progesterone to prepare the uterus for implantation of an embryo. If the egg cell is not fertilized or the fertilized egg cell does not implant, the corpus luteum regresses after 14 days and a new menstrual cycle begins. “Our results show that ovulation is a remarkably robust process. Although an external stimulus is essential for triggering ovulation, the subsequent processes occur independently of the rest of the ovary because all the necessary information is contained in the follicle itself,” says Schuh. “With our new method, we and other researchers can further investigate the mechanisms of ovulation and hopefully gain new insights for human fertility research.”