Approximately 400 times in a woman’s life, a mature egg makes the “leap.” It is released into the fallopian tube, ready for fertilization by the sperm. Researchers led by Melina Schuh, Christopher Thomas, and Tabea Lilian Marx from the Max Planck Institute (MPI) for Multidisciplinary Sciences have now succeeded in visualizing the entire process of ovulation in mouse follicles in real-time. The new live imaging method developed by the team allows for the process to be studied with high spatial and temporal resolution, contributing to new insights in fertility research.
During a woman’s fertile phase, 15 to 30 eggs mature per menstrual cycle inside fluid-filled sacs called follicles. As they mature, the eggs are supported by specialized cells within the follicle, known as cumulus cells. However, only the largest and best-developed follicle makes it to ovulation. The follicle ruptures, and the egg is released into the fallopian tube. If successfully fertilized by a sperm cell within 24 hours of ovulation, the egg travels to 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 interplay of hormones, yet the actual process of ovulation remains poorly understood. The ovary lies deep within the body, making it experimentally challenging to access. Additionally, ovulation occurs within a very narrow time frame, 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 from mice under the microscope with high spatial and temporal resolution. “We can distinguish three phases,” explains Max Planck Director Melina Schuh, head of the Department of Meiosis. “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 tracked 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 group leader at the Institut de Biologie du Développement in Marseille (France) and co-first author of the study published in Nature Cell Biology. 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 essential for ovulation
The image shows an egg that has just been ovulated next to the follicle.
© Christopher Thomas, Tabea Lilian Marx et al. / Max Planck Institute for Multidisciplinary Sciences
In the second phase, follicle contraction, smooth muscle cells in the outer follicle layer cause the follicle to contract. When the team inhibited the contraction of these muscle cells, the follicles failed to contract – again with serious consequences for the egg. “In this case too, ovulation failed,” Thomas says.
“When the follicle ruptures, which happens in the third phase, the egg is released and ovulation is complete,” explains Tabea Lilian Marx, also a co-first author and a doctoral student in the Department of Meiosis. “The surface of the follicle bulges outward and eventually ruptures, releasing the follicular fluid, the cumulus cells, and, finally, the egg,” she explains.
After ovulation, the follicle forms a structure known as the corpus luteum, which produces the hormone progesterone to prepare the uterus for the implantation of an embryo. If the egg is not fertilized or if the fertilized egg does not implant, the corpus luteum regresses after 14 days, and a new menstrual cycle begins.
New findings for fertility research
“Our findings show that ovulation is a remarkably robust process. Although an external stimulus is essential to trigger ovulation, the subsequent processes operate independently of the rest of the ovary, as all the necessary information is contained within 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.”
