Scientists from the Washington University School of Medicine in St. Louis have discovered the previously unknown role of a specific gene in fertility problems and early menopause.
A study, published last month in the journal Science Advances, found that fruit flies, roundworms, zebrafish and mice were found to be sterile because they lacked that gene. The study also found a link between mutations in this gene and early menopause.
The gene, called nuclear envelope membrane protein 1 (NEMP1), hasn’t been studied much. In animals, mutations in this gene had been associated with impaired eye development in frogs.
Senior author of the study, Dr Helen McNeill, said, “We blocked a gene expression in the fruit flies, but we found that their eyes were fine. So, we started trying to figure out what other problems they might have. these animals. They looked healthy, but to our surprise it turned out that they were completely sterile. We found that they had substantially defective reproductive organs. “
Both males and females had fertility problems when this gene was missing, especially in females, the team found that the envelope of the gene contains the nucleus of the egg, which looked like a floppy balloon.
Dr McNeill explained, “This gene is expressed throughout the body, but we haven’t seen this floppy balloon structure in the nuclei of other cells. This was a clue that we came across a gene that has a specific role in fertility. “
“We saw the impact before in flies, but we knew that proteins are shared between species,” he added. “With a group of wonderful collaborators, we have also eliminated this gene in worms, zebrafish and mice. It is so exciting to see that this protein which is present in many cells in the body plays such a specific role in fertility. It’s not a big leap to suspect that it also plays a role in people. “
“It is interesting to ask whether the rigidity of the nuclear egg envelope is also important for fertility in people,” continued Dr. McNeill. “We know that there are variants in this gene associated with early menopause. And when we studied this defect in mice, we see that their ovaries have lost the pool of oocytes they were born with, which determines their lifelong fertility. “
“Hence, this finding provides a potential explanation for why women with mutations in this gene could have premature menopause. When you lose your egg supply, you go into menopause. “
He continued explaining, “If you have a softer core, maybe it can’t handle that environment. This could be the signal for egg death. We don’t know yet, but we are planning studies to answer this question. “
Dr. McNeill and her team discovered just one more problem with mice lacking this gene. They were anemic, meaning they lacked red blood cells.
He explained: “Normal adult red blood cells lack a nucleus. There is a stage where the nuclear envelope has to condense and be expelled from the young red blood cell as it develops in the bone marrow. The red blood cells in these mice do not. correctly and die at this stage. With a floppy nuclear envelope, we think that young red blood cells do not survive in another mechanically stressful situation. “
“We can target these stem cells to become eggs and see what effect these mutations have on the nuclear envelope,” continued Dr. McNeill. “It is possible that there are perfectly healthy women around who lack the NEMP protein.” “If this proves to cause infertility, at least this knowledge might offer an explanation. If women without NEMP are found to be infertile, more research needs to be done before you can start asking if there are ways to correct these mutations – restore NEMP, for example, or find another way to support wrap stiffness. nuclear “.