Chemotherapy’s anti-cancer effects depend on its ability to damage rapidly growing cells, which is beneficial when targeting cancer cells that multiply rapidly. However, chemotherapy also causes collateral damage to other types of rapidly growing cells, including cells found in the ovaries. A naturally occurring hormone that plays an important role in fetal development, called Mullerian Inhibiting Substance (MIS), may be effective in not only preventing pregnancy during chemotherapy (which is not recommended because of the potential for drugs to harm the developing baby), but also can protect immature egg cells and potentially reduce the risk of infertility down the line.
A team from the Pediatric Surgical Research Laboratories in the Massachusetts General Hospital Department of Surgery found that boosting MIS levels can pause the early development of ovarian follicles when egg cells are maturing, thus protecting them from chemotherapy-induced damage. When MIS levels were increased in a series of experiments with female mice, researchers saw a significant decrease in the number of growing follicles. After several weeks, there was an almost complete lack of growing follicles. When the treatment stopped, the follicle development process resumed, showing that the effect is reversible.
These findings were unexpected for researchers, who were previously unaware of MIS’ ability to block the entire follicular development process. The results also provide new hope for preserving fertility in women undergoing chemotherapy. In addition to damaging cells found in the ovaries, chemotherapy speeds up natural ovulation processes, essentially using up the reserve of immature eggs in a matter of months rather than years. The ability to potentially maintain the larger pool of eggs not only could maintain fertility during chemotherapy but also could be applied to modern fertility treatments and contraceptives.
Researchers have just started to scratch the surface of the implications of MIS for reproductive and overall health. MIS could potentially prove useful in treating many conditions that cause ovarian insufficiency or premature menopause.
Motohiro Kano, MD, of the Massachusetts General Hospital Department of Surgery, is lead author of this study. Patricia K. Donahoe, MD and David Pepin, MD, are corresponding authors.