News | Mitochondrial Abnormalities May Be a Treatment Target for Primary Ovarian Insufficiency
About 48 million couples worldwide experience infertility, which has many causes. In mammals, including humans, eggs develop in the ovaries. Problems in this process can cause female infertility. One example is primary ovarian insufficiency (POI), characterized by impaired egg production before age 40. It affects about 3.7% of women, and genetic variants account for around 30% of cases. Professor Kehkooi Kee of Tsinghua University in China has studied the condition for years. He said that in 2019, Professor Li's team identified a family with POI that appeared to be linked to a change in a gene called Eif4enif1. Researchers replicated the genetic change in mice to understand how it might affect human infertility. The mice's eggs showed mitochondrial changes; mitochondria are the cell's “powerhouses.” The findings were published in Development on December 13, 2023.
Researchers used CRISPR to introduce the genetic change into mice, allowed them to mature, and compared their fertility with mice whose DNA was not edited. First author and MD/PhD student Yuxi Ding found that older gene-edited mice had about 40% fewer total follicles, the small sacs containing developing eggs, and produced 33% fewer pups per litter on average. When the eggs were grown in laboratory dishes, about half of the fertilized eggs did not survive early development. Like the affected human patients, the mice had fertility problems.
Under a microscope, the researchers observed abnormal mitochondria in the eggs. Mitochondria provide energy to cells, including egg cells, and are normally distributed evenly throughout an egg. In eggs from mice with the variant, they clustered together.
Professor Kee said the team was surprised by the mitochondrial differences because no link between Eif4enif1 and mitochondria had been identified when the study began.
The researchers believe that abnormal mitochondrial behavior may cause the fertility problems and propose that restoring normal mitochondrial behavior could improve fertility. Future research could determine whether similar defects occur in eggs from people with POI and persist in embryos after fertilization. Testing whether normal mitochondrial distribution can be restored may offer a new treatment strategy. Professor Kee said correcting oocyte mitochondrial abnormalities may be a potential treatment target for patients with infertility caused by genetic variants.
News | Mitochondrial Abnormalities May Be a Treatment Target for Primary Ovarian Insufficiency
News | Mitochondrial Abnormalities May Be a Treatment Target for Primary Ovarian Insufficiency
About 48 million couples worldwide experience infertility, which has many causes. In mammals, including humans, eggs develop in the ovaries. Problems in this process can cause female infertility. One example is primary ovarian insufficiency (POI), characterized by impaired egg production before age 40. It affects about 3.7% of women, and genetic variants account for around 30% of cases. Professor Kehkooi Kee of Tsinghua University in China has studied the condition for years. He said that in 2019, Professor Li's team identified a family with POI that appeared to be linked to a change in a gene called Eif4enif1. Researchers replicated the genetic change in mice to understand how it might affect human infertility. The mice's eggs showed mitochondrial changes; mitochondria are the cell's “powerhouses.” The findings were published in Development on December 13, 2023.
Researchers used CRISPR to introduce the genetic change into mice, allowed them to mature, and compared their fertility with mice whose DNA was not edited. First author and MD/PhD student Yuxi Ding found that older gene-edited mice had about 40% fewer total follicles, the small sacs containing developing eggs, and produced 33% fewer pups per litter on average. When the eggs were grown in laboratory dishes, about half of the fertilized eggs did not survive early development. Like the affected human patients, the mice had fertility problems.
Under a microscope, the researchers observed abnormal mitochondria in the eggs. Mitochondria provide energy to cells, including egg cells, and are normally distributed evenly throughout an egg. In eggs from mice with the variant, they clustered together.
Professor Kee said the team was surprised by the mitochondrial differences because no link between Eif4enif1 and mitochondria had been identified when the study began.
The researchers believe that abnormal mitochondrial behavior may cause the fertility problems and propose that restoring normal mitochondrial behavior could improve fertility. Future research could determine whether similar defects occur in eggs from people with POI and persist in embryos after fertilization. Testing whether normal mitochondrial distribution can be restored may offer a new treatment strategy. Professor Kee said correcting oocyte mitochondrial abnormalities may be a potential treatment target for patients with infertility caused by genetic variants.
Source:
Collected online