by female infertility affects millions of couples worldwide, and its causes can vary. In mammals, including humans, the ovaries play a crucial role in the production of eggs. When this process malfunctions, it can lead to female infertility. One specific condition associated with this is premature ovarian insufficiency, where there are issues with egg production before the age of 40. Genetic variations are responsible for approximately 30% of cases of infertility in relation to this condition.
Professor Kehkooi Kee from Tsinghua University in China has been studying premature ovarian insufficiency for several years. In 2019, Professor Kee’s collaborators, led by Professor Li, identified changes in a gene called Eif4enif1 in a family experiencing premature ovarian insufficiency. These changes in the gene were believed to be responsible for the disease. Intrigued by this discovery, the researchers decided to replicate the genetic alteration in mice to delve deeper into how it affects female infertility. The findings of their study have been published in the journal Development.
Using CRISPR technology, the researchers introduced the genetic change into the mice. Once the mice had matured, the researchers compared their fertility to that of mice whose DNA had not been edited. The study’s lead author, Yuxi Ding, found that older genetically modified mice had a reduction of approximately 40% in the average number of total follicles (developing egg sacs). Additionally, the average number of pups per litter was reduced by 33%.
Of particular interest, roughly half of the fertilized eggs grown in a laboratory dish did not progress beyond the early stages of development. This mirrored the fertility issues observed in human patients with premature ovarian insufficiency. In examining the eggs under a microscope, the researchers made an intriguing discovery. They noticed that the mitochondria, the energy-producing powerhouses of cells, exhibited an abnormal clustering in the eggs of mice with the genetic variation. Typically, mitochondria are evenly distributed throughout an egg.
Professor Kee expressed surprise at the differences in the mitochondria, as no previous link had been established between Eif4enif1 and mitochondria. This observation strongly suggests that these misbehaving mitochondria may contribute to fertility problems in mice with the genetic alteration. Consequently, the researchers propose that restoring normal mitochondrial behavior could potentially enhance fertility.
This study opens up avenues for future research in understanding human infertility. There is a need to determine whether mitochondrial defects are present in the eggs of human patients with premature ovarian insufficiency and whether the same mitochondrial abnormalities are observed in embryos after fertilization. Additionally, exploring whether restoring the normal distribution of mitochondria can improve fertility could become a novel treatment strategy.
Professor Kee emphasizes the implications of their findings, stating, “Our research suggests that rescuing oocyte mitochondria abnormality could be a potential therapeutic target for clinical infertility patients with genetic variants.” This breakthrough offers hope for couples facing infertility and provides valuable insights for developing targeted interventions in the future.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
