Keyword

Start publishing date

-

Tag

Meta Title

Header h1

Friday, 25 June 2021 07:03

Genetic Mutations and Fertility: Considerations and Implications

Genetic mutations found in humans, fruit flies, roundworms, zebrafish, and mice may be linked to fertility issues and early menopause.

September 01, 2020 - A team from Washington University School of Medicine in St. Louis has identified genetic mutations that may be associated with infertility and early menopause.
The study, published in the journal Science Advances, was initially conducted to find the genes involved with eye development in the early embryos of fruit flies.

“We blocked some gene expression in fruit flies but found that their eyes were fine,” said senior author Helen McNeill, PhD, the Larry J. Shapiro and Carol-Ann Uetake-Shapiro Professor and a BJC Investigator at the School of Medicine. “So, we started trying to figure out what other problems these animals might have. They appeared healthy, but to our surprise, it turned out they were completely sterile. We found they had substantially defective reproductive organs.”
The equivalent of this gene in humans is known as nuclear envelope membrane protein 1 (NEMP1), and researchers noted that it is not widely studied.

The team found that when the gene is missing in fruit flies, roundworms, zebrafish, and mice, the animals are infertile or lose their fertility unusually early but appear otherwise healthy. In people, researchers found a link between mutations in this gene and early menopause.
Although it varied a bit by species, males and females both had fertility problems when missing this gene. In females, researchers found that the envelope that contains the egg’s nucleus – the compartment that holds half of an organism’s chromosomes – resembled a floppy balloon.
“This gene is expressed throughout the body, but we didn’t see this floppy balloon structure in the nuclei of any other cells. That was a hint we’d stumbled across a gene that has a specific role in fertility,” said McNeill, also a professor of developmental biology.

“We saw the impact first in flies, but we knew the proteins are shared across species. With a group of wonderful collaborators, we also knocked this gene out in worms, zebrafish and mice. It’s so exciting to see that this protein that is present in many cells throughout the body has such a specific role in fertility. It’s not a huge leap to suspect it has a role in people as well.”
Researchers used a technique called atomic force microscopy to poke a needle into the cells, first penetrating the outer membrane and then the nucleus’s membrane. The amount of force required to penetrate the membranes gives scientists a measure of their stiffness, the nucleus’s membrane was much softer.

“It’s interesting to ask whether stiffness of the nuclear envelope of the egg is also important for fertility in people,” McNeill said.

“We know 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 egg cells that they’re born with, which determines fertility over the lifespan. So, this finding provides a potential explanation for why women with mutations in this gene might have early menopause. When you lose your stock of eggs, you go into menopause.”

The team suspects that the nuclear envelope has to find a balance between being pliant enough to allow the chromosomes to align as they should for reproductive purposes, but stiff enough to protect them from the ovary’s stressful environment. With age, ovaries develop strands of collagen with potential to create mechanical stress not present in embryonic ovaries.
“If you have a softer nucleus, maybe it can’t handle that environment,” McNeill said. “This could be the cue that triggers the death of eggs. We don’t know yet, but we’re planning studies to address this question.”

In conducting these studies, the only one other problem researchers found with the mice missing this specific gene was anemia, meaning they lacked red blood cells.
“Normal adult red blood cells lack a nucleus,” McNeill said. “There’s a stage when the nuclear envelope has to condense and get expelled from the young red blood cell as it develops in the bone marrow. The red blood cells in these mice aren’t doing this properly and die at this stage. With a floppy nuclear envelope, we think young red blood cells are not surviving in another mechanically stressful situation.”

Going forward, the team wants to investigate whether women with fertility problems have mutations in NEMP1. They have developed human embryonic stem cells that were given specific mutations in NEMP1 listed in genetic databases as associated with infertility.
“We can direct these stem cells to become eggs and see what effect these mutations have on the nuclear envelope. It’s possible there are perfectly healthy women walking around who lack the NEMP protein,” said McNeill.

“If this proves to cause infertility, at the very least this knowledge could offer an explanation. If it turns out that women who lack NEMP are infertile, more research must be done before we could start asking if there are ways to fix these mutations — restore NEMP, for example, or find some other way to support nuclear envelope stiffness.”

By Jessica Kent

Read 1896 times

Making Motherhood Possible: Safely Moving Life's Precious Cargo

Embryo transfer has become a focal point of discussion for many intended parents, especially when considering the logistics and concerns surrounding the movement of frozen embryos between IVF clinics. These embryos symbolize not just a significant financial and time investment but also the hopes and dreams of countless individuals and…

Why Frozen Embryo Transfers are overtaking Fresh Embryo Transfers?

According to a recent report from the HFEA features a pattern towards Assisted Reproductive Technology (ART) enlistments across the globe. It states that frozen embryo transfer has been increasingly seen as a mainstream embryo transfer protocol. HFEA measurements depict that fresh embryo transfers dropped by 11 percent somewhere in the…

Nancy Linnerooth, Procrastination Coach and EFT Tapping Specialist

Overcoming Stress and Decision Making in the Surrogacy Journey and EFT/Tapping Delivering Dreams International Surrogacy Agency Welcomes EFT/Tapping Expert Coach Nancy Linnerooth to a live interview broadcast Wednesday Nov. 6 at 10:00 AM EST. This premier live interview is free to all. To participate, join Delivering Dreams’ Facebook group for…

Testimonials

I am very satisfied with the medical services. Coordinator Lyubov was always in touch, answered any questions quickly and clearly, and helped in any difficult situations. The level of personal support and genuine concern for my health and well-being was 100 percent. I am very pleased that I am going through the surrogacy program with this agency. I feel protected and confident. I really like the attitude of the agency, timely payments, and the curator and manager make sure that pregnant girl...
Read more
Olga T.
I am very pleased to meet such beautiful and kind people Hello everyone, I'm Myroslava and I'm going through my SM program at the Delivering Dreams agency. I want to express a big thank you to the girls who cooperate with me, who worry about my condition, who are always in touch, and who always support me - Omelchuk Lyubov and Anna Levchenko. I've already been to a program and therefore I have something to compare it with, this agency and the staff are at the highest level. And also the doct...
Read more
Myroslava
Hallo Oksana,  vielen Dank für Deine ausführliche Erklärung. Wir haben alles gut verstanden. Das zeichnet due Arbeit von Euch und Eurem Ärzteteam aus. So kann man gut vertrauen. Hello Oksana, Thank you very much for your detailed explanation. We understood everything well. This is what distinguishes the work of you and your medical team. This is a good way to trust.
German couple
One of the best teams and my program! Hello! I want to share my experience and my impression of my program, one of the best programs, and the team from the Delivering Dreams Agency! Great attitude, attentive staff, responsible! Always in touch 24/7! Lyubov Omelchuk is a wonderful person, she was with me from the first minute of implantation until the end of the entire program! I am grateful that Lyubov was always with me! People of their word! Staff who never let you down! I highly recommend...
Read more
Anna Priazhnikova
DD is outstanding We have just returned home to California with our beautiful daughter who was born in Lviv. The Delivering Dreams team made our trip so easy and straightforward. From our arrival to Ukraine to our departure, they had everything covered. The constant communication from the team is amazing. All of our paperwork for the embassy was properly prepared and organized. I cannot recommend them enough, we are even thinking about having another baby with DD!
Andrey Frenkel
Thank you very much Dear Oksana, Thank you very much for the great news. We still can't believe it and are totally speechless. The work you do under these difficult conditions cannot be put into words. Thank you very much for that. Liebe Oksana, vielen Dank für die super schöne Neuigkeit. Wir können es noch gar nicht glauben und sind total sprachlos. Was Ihr für eine Arbeit leistet, unter den schweren Bedingungen,  kann man nicht in Worte fassen. Vielen herzlichen Dank dafür.
Couple from Germany
Very friendly, pleasant team I am very grateful to the international surrogacy agency Delivering Dreams for such a short period of experience that dispelled all doubts and the remains of incomprehensible questions that were before and during this program, but I had a wonderful curator Lyuba who did not leave me for a second even on distances?❤️ This is how experienced, pleasant, kind woman you want to go to the program at least immediately after finishing the first one! Very friendly, pleasa...
Read more
Angelina
Thank you for the wonderful experience and the opportunity to help future parents. I also want to thank Lyubov Omelchuk (Delivering Dreams) for her kindness and empathy, she was always in touch throughout the program, especially since the rehabilitation course is based on the supervision and advice of the curator. My worries about the procedure were in vain because everything went perfectly, thanks to the 24/7 support of the curator and qualified doctors Дякую за чудовий досвід, та змогу...
Read more
Angelina
I recommend this agency. I was a surrogate mother in this agency, I really liked everything. The doctors treated me well and explained everything clearly. Curator Lyuba and Anya are always in touch and answer all questions, always supporting. I recommend this agency. Я була сур мама в цьому агентство, мені все дуже сподобалося лікарі гарно відносяться, розповідають все доступно. Куратор Люба і Аня завжди на зв'язку і відповідать на всі запитання, завжди підтримують. Рекомендую це агентство.
Yuliia
Thank you very much for worrying about me.  I really want to start the program at Delivery Dreams agency. The doctors here are extraordinary. Coordinator Lyubov is also extraordinary, always in touch and worries about me. After the hysteroscopy, Lyubochka is on the phone with me 24/7. Thank you very much for worrying about me. I hope that my program will start soon and I will present the baby to the biological parents. Thank you for being there!?? Я дуже хочу почати програму в агенстві De...
Read more
Nastya

Under Ukrainian law, surrogacy is a legal affordable option for traditionally married couples to have children using their own embryos, or with either an egg or sperm donor. There must be a medical reason you can’t carry a child. You are also able to participate if you have had 4 unsuccessful IVF attempts.

CONTACT US

Under Ukrainian law, surrogacy is a legal affordable option for traditionally married couples to have children using their own embryos, or with either an egg or sperm donor. There must be a medical reason you can’t carry a child. You are also able to participate if you have had 4 unsuccessful IVF attempts.