How to safeguard fertility during chemotherapy?

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Washington D.C.: A research has decoded the mechanism of chemotherapy-induced female infertility. The researchers from the Goethe University Frankfurt deciphered the mechanism leading to premature loss of the oocyte pool caused by treatment with chemotherapy.

Many chemotherapeutics act by damaging the DNA. Since cancer cells divide more often than most normal cells, they react more sensitive to DNA damaging agents. One exception is oocytes.

To prevent birth defects they initiate a cellular death program if DNA damage is detected. This process, called apoptosis, is triggered in oocytes by the protein p63. Oocytes contain a high concentration of an oocyte-specific isoform of p63 which plays a key role as a quality control factor in causing infertility.

In contrast to men who produce new sperm cells throughout their life women are born with a finite number of oocytes. When this pool is depleted menopause starts. This pool of oocytes can be depleted prematurely by chemotherapy resulting in early menopause. This results not only in infertility but also in hormone-based problems such as osteoporosis.

In non-damaged oocytes, p63 exists in an inactive form. DNA damage caused by chemo- or radiotherapy results in the modification of p63 with phosphate groups which triggers a conformational change to the active form.

Active p63 starts the cell death program which leads to the elimination of the oocyte. These results open new opportunities for developing a therapy for preserving oocytes of female cancer patients treated with chemotherapeutics.

The study appears in the online edition of the journal Nature Structural and Molecular Biology.

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