Lead author, Dr. Daylon James, assistant professor of stem cell biology in obstetrics and gynecology and reproductive medicine at Weill Cornell Medicine.
“A better understanding of the root causes of PCOS is critical to mitigating the many health consequences of the condition.”
Developing eggs, called oocytes, are produced in the ovaries in the follicles, which aid in their development. As the follicle develops, the egg that lives within it gradually matures, and during a normal reproductive cycle, that follicle eventually undergoes ovulation to release a potentially fertilized egg. However, in patients with PCOS, a hormonal disorder that affects up to 10% of women, the ovaries contain many smaller follicles that produce AMH, but do not progress to later stages and ovulation.
While fertility treatments can help conceive, women with PCOS face a host of other symptoms, Dr. For example, PCOS is often accompanied by hyperandrogenism, or high levels of hormones like testosterone known collectively as androgens. An excess of these hormones can cause a host of secondary complications, including unwanted body and facial hair growth. Women with PCOS may also be more susceptible to diabetes and metabolic disease and to endometrial cancer.
Dr. James and his research team hypothesized that AMH directly contributes to at least some of the symptoms associated with this disorder. To isolate the effects of AMH, the researchers used a xenograft system in which ovarian tissue from human organ donors was etched into the flanks of immunocompromised mice. One group of mice were transplanted with cells that continuously delivered AMH directly to the graft, and the other group of mice were transplanted with AMH-free control cells.
“What we have here is a unique opportunity to take tissue from the same donors and distribute it to both experimental groups — the group with AMH and the group without AMH,” said the first author, Dr. Limor Man, research assistant professor of obstetrics and gynecology and reproductive medicine, and Hung-Ching Liu Research Scholar in Obstetrics and Gynecology. “This is really the best control you can hope for in these kinds of tests.”
In contrast, when researchers compare patients with PCOS with those without the disorder in clinical studies, multiple influencing factors must be considered, such as genetic predisposition and variability in different reproductive hormones, she says.
The researchers found that ovarian tissue exposed to high levels of AMH contained follicles that showed features that were evident at a much later stage of development. Specifically, the follicles are undergoing lutealization, a process that occurs immediately leading to ovulation, before any egg cells are ready.
Dr James, Queenie Victorina Neri Research Scholar in Obstetrics and Gynecology and Assistant Professor of Genetic Medicine at Weill Cornell Its resident oocytes are asynchronous. Medicine. “It’s like baking with an oven that’s too hot,” he say. “The outside, or cellular component of the follicle, is overcooked, while the inside, or egg cell, is left uncooked.”
“Based on ultrasound showing the persistent presence of many small cysts in the ovaries, infertility in women with PCOS is thought to be due to stalled growth and unsuccessful egg maturation.” Dr. Man said. “But recent data indicate that the ‘stagnation’ cysts in these patients are actually a steady stream of newly-developed but aborted follicles.”
This new study offers a modified interpretation that the series of persistent small follicles in the PCOS ovaries represent a continuum of follicles that are undergoing accelerated maturation and are unable to ovulate.
Considering the widespread prevalence of PCOS, the factors that contribute to its occurrence are still poorly understood. Although treatments exist for each aspect of the disease, the condition rarely goes into remission until a woman is past her childbearing age. The identification of a novel AMH driver for failed follicular development suggests that it may contribute to this, and perhaps other aspects of PCOS disease symptoms.
“With further research, we hope to develop drug treatments that target the effects of AMH, which may help restore menstrual cycles in women with PCOS and control other symptoms of AMH. This situation”. Dr. James said.