On November 15th, it was learned from Nankai University that a groundbreaking study conducted by the School of Life Sciences and the National Key Laboratory of Medicinal Chemistry Biology, Developmental Biology, and Stem Cell Team, has brought hope for women who suffer from infertility due to age or unknown reasons to conceive. Research has revealed in depth the age molecular clock - ribosome dysregulation - behind the decline in fertility in women after the age of 34, and preliminarily validated that the drug rapamycin can be a potential, safe, and effective treatment method to help patients with repeated in vitro fertilization failures achieve successful pregnancy and live birth. This indicates that rapamycin may bring new breakthroughs in infertility treatment. This important research was jointly conducted by the Nankai team, Shanxi Children's Hospital (Shanxi Maternal and Child Health Hospital), the Sixth Medical Center of the General Hospital of the People's Liberation Army of China, Tianjin Medical University General Hospital, and other units. The relevant results were published in the international journal Cell Reporter Medicine. As is well known, women's fertility decreases with age, especially after the age of 34. But the specific reasons behind it, especially many cases of "unexplained" infertility, have been troubling scientists and doctors. The team's research shows that significant transcriptome changes occur in the oocytes and surrounding cumulus cells of women after the age of 34. One of the most prominent features is the abnormally elevated transcription level of ribosomal genes. At the same time, the expression of genes related to meiosis, actin, and mucin is downregulated in oocytes, and lysosomal activity is reduced and protein homeostasis is disrupted in cumulus cells. Our work suggests that abnormal ribosome function is a previously overlooked driving force behind the decline in egg quality. ”Li Jie, the first author of the paper and a 2020 doctoral graduate in Cell Biology from Nankai University, said. Further research revealed that the "overactivity" of ribosomal genes is closely related to epigenetic loss of control - specific genomic loci exhibit DNA hypomethylation and local reduction of H3K9me3 heterochromatin, similar to the disorder of the instruction system controlling gene "switches" in the nucleus, leading to abnormally high expression of ribosomal genes and increased synthesis of abnormal proteins. Based on these results, the research team attempted to conduct intervention experiments on mice using the drug rapamycin, which has the effects of inhibiting ribosome translation and intervening in aging. The results indicate that rapamycin can effectively reduce intracellular translation activity and reshape protein homeostasis, thereby improving the ovarian microenvironment and egg quality. In addition, this study has also been validated in clinical applications. The research team conducted a randomized controlled trial and confirmed that short-term treatment with rapamycin can enable women who have repeatedly failed in vitro fertilization and experienced embryonic development arrest to obtain high-quality blastocysts, and successfully achieve pregnancy and live birth. Wu Xueqing, director of the Reproductive Medicine Center at Shanxi Children's Hospital, said, "This preliminary result is encouraging and opens up a new path for understanding and treating age-related infertility. In the future, we still need to carry out larger scale, multi center clinical trials to further verify its efficacy and optimize treatment plans