Infertility affects around 48 million couples worldwide.
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Professor Kehkooi Kee, from Tsinghua University, China, who helped lead a new study on this topic, has been investigating this condition for several years.
The researchers decided to reproduce this genetic change in mice to try to understand how it affects human infertility.
They show that the eggs of these mice are affected by changes to their mitochondria, the powerhouses of the cell. Their work around this new discovery is published in Development.
"Premature ovarian insufficiency (POI) refers to loss of ovarian function before 40 years of age and is a contributing factor to infertility. Several case studies have reported dominant-inherited POI symptoms in families with heterozygous EIF4ENIF1 (4E-T) mutations.
"However, the effects of EIF4ENIF1 haploinsufficiency have rarely been studied in animal models to reveal the underlying molecular changes related to infertility.
"Here, we demonstrate that Eif4enif1 haploinsufficiency causes mouse subfertility, impairs oocyte maturation and partially arrests early embryonic development.
"Using dual-omic sequencing, we observed that Eif4enif1 haploinsufficiency significantly altered both transcriptome and translatome in mouse oocytes, by which we further revealed oocyte mitochondrial hyperfusion and mitochondria-associated ribonucleoprotein domain distribution alteration in Eif4enif1-deficient oocytes.
"This study provides new insights into the molecular mechanisms underlying clinical fertility failure and new avenues to pursue new therapeutic targets to address infertility."
When the researchers studied the eggs from these mice under the microscope, they noticed something unusual about their mitochondria. Mitochondria produce the energy that cells including egg cells need.
"Our research suggests that rescuing oocyte mitochondria abnormality could be a potential therapeutic target for clinical infertility patients with genetic variants," says Professor Kee. ■