Discovery may lead to better egg screening and IVF outcomes

February 9, 2016 by Laura Kurtzman

Experts in in-vitro fertilization (IVF) from UC San Francisco have discovered a pattern of protein secretion during egg maturation that they say has the possibility of leading to a new, non-invasive test to evaluate the fitness of eggs before they are fertilized in the clinic.

In studies of mouse and human , Hakan Cakmak, MD, an assistant professor with the Department of Obstetrics, Gynecology and Reproductive Sciences and the Center for Reproductive Sciences at UCSF and a team of investigators from the same department and center, led by Marco Conti, MD, a professor and the director of the center, have discovered a previously unrecognized pattern of protein secretion by a woman's eggs that normally occurs during their maturation. This secretion plays a vital role in communication between the egg and its supporting cells during the final phase of development, around the time of ovulation, according to the researchers. Their new study was published online on Feb. 8 in the Proceedings of the National Academy of Sciences (PNAS).

The UCSF researchers next intend to measure secretion of some of these proteins by the egg during IVF, so that they can later determine whether, as they suspect, at least some percentage of eggs that are used in procedures that do not result in successful pregnancies turn out to have had abnormal patterns of protein secretion.

If that is the case, a test based on sampling fluid surrounding the egg could be used to better gauge egg fitness much earlier in the IVF process, without risking harm to the embryo with invasive testing, according to Cakmak. "Next steps involve seeing whether the patterns we have observed are predictive of IVF pregnancy outcome," he said.

In what has become a standard procedure at IVF clinics, five to six days after fertilization embryologists perform a needle biopsy to remove several of the cells in the embryo and check them for chromosome abnormalities, almost all of which can be attributed to faulty egg maturation prior to fertilization, Cakmak said. This embryo biopsy procedure is not entirely without risk to the embryo.

The UCSF researchers used advanced lab techniques to assess secreted proteins that guide the final stages of egg maturation, a process which involves completion of a type of cell division, called meiosis, that in sexually reproducing animals only occurs in eggs and sperm and which results in an egg that is "haploid," meaning that it contains only one copy of each chromosome instead of the pairs of chromosomes found in other, "diploid" cell types. If all goes well, normal chromosome pairs are again formed after sperm and egg join forces through fertilization.

The signaling needed for the completion of meiosis is a kind of chemical conversation between the egg—called an oocyte—and cells that surround it, called cumulus cells. They are obtained together as an intact unit when eggs are harvested for IVF following hormonal stimulation.

"Oocyte fitness to support embryo development and pregnancy is dependent on an elaborate crosstalk with the surrounding environment," Cakmak said. "Most defects in oocyte development occur during this time, and they are more likely to occur in older women."

In mice and humans, the researchers tracked changes in oocyte secretion through the final stage of oocyte maturation—triggered by a burst of luteinizing hormone from the brain's pituitary gland—before fertilization.

Conti's team measured translation of messenger RNA, a step following gene activation that results in protein production, and found that translation of 125 messenger RNAs encoding secretory proteins changed in the oocyte from the time of the luteinizing hormone burst through fertilization.

The researchers also were able to detect a secretory spurt not previously observed by others during the final stage of meiosis and oocyte maturation. It had been known that the oocyte stops activating genes to make RNA, a process called transcription, during the last stages of maturation. But by probing oocytes' protein-making machinery Conti's team found that these late-stage oocytes still ramp up production of some proteins by using pre-existing RNA. The interaction between cumulus cells and oocytes guides this late production and secretion of protein during the oocyte's final maturation, even while no new RNA is produced, Cakmak said.

The researchers are weighing which of the proteins that undergo dramatic changes in secretion to include in a new assay to test for normal oocyte maturation. In the PNAS study, they focused most intensely on one candidate, called interleukin-7 (IL-7).

In the mouse they found that IL-7 secretion depends on its RNA being translated into protein within the oocyte, and that this translation is controlled by cumulus cells. In a feedback loop, IL-7 directs division of . Working with human oocytes, they found that the amount of IL-7 measured in fluid obtained from follicles during egg extraction was related to the oocyte's ability to fully mature.

"We can detect these proteins in tiny amounts, on the order of one-trillionth of a gram, in a tiny drop, which in the past we could not do," Cakmak said.

Explore further: In vitro fertilization using frozen eggs associated with lower live birth rates

More information: Dynamic secretion during meiotic reentry integrates the function of the oocyte and cumulus cells: Role of mRNA translation,

Related Stories

In vitro fertilization using frozen eggs associated with lower live birth rates

August 11, 2015
Compared to using fresh oocytes (eggs) for in vitro fertilization, use of cryopreserved (frozen) donor oocytes in 2013 was associated with lower live birth rates, according to a study in the August 11 issue of JAMA.

Mutations in TUBB8 linked to form of female infertility

January 21, 2016
(HealthDay)—For a small number of women with a rare form of infertility, mutations in a particular gene may be the cause, according to a study published in the Jan. 21 issue of the New England Journal of Medicine.

Researchers identify protein in mice that helps prepare for healthy egg-sperm union

July 27, 2015
Researchers at the National Institutes of Health have discovered a protein that plays a vital role in healthy egg-sperm union in mice. The protein RGS2 can delay an egg's development into an embryo in order to allow time ...

A new method for picking the 'right' egg in IVF

June 1, 2012
(Medical Xpress) -- In a groundbreaking study, Yale School of Medicine researchers and colleagues at the University of Oxford have identified the chromosomal make-up of a human egg. This discovery may soon allow them to avoid ...

Researchers identify molecule that protects women's eggs

October 7, 2014
A new study led by Professor Kui Liu at the University of Gothenburg has identified the key molecule 'Greatwall kinase' which protects women's eggs against problems that can arise during the maturation process.

Recommended for you

Common antiseptic ingredients de-energize cells and impair hormone response

August 22, 2017
A new in-vitro study by University of California, Davis, researchers indicates that quaternary ammonium compounds, or "quats," used as antimicrobial agents in common household products inhibit mitochondria, the powerhouses ...

Make way for hemoglobin

August 18, 2017
Every cell in the body, whether skin or muscle or brain, starts out as a generic cell that acquires its unique characteristics after undergoing a process of specialization. Nowhere is this process more dramatic than it is ...

Bio-inspired materials give boost to regenerative medicine

August 18, 2017
What if one day, we could teach our bodies to self-heal like a lizard's tail, and make severe injury or disease no more threatening than a paper cut?

Are stem cells the link between bacteria and cancer?

August 17, 2017
Gastric carcinoma is one of the most common causes of cancer-related deaths, primarily because most patients present at an advanced stage of the disease. The main cause of this cancer is the bacterium Helicobacter pylori, ...

Two-step process leads to cell immortalization and cancer

August 17, 2017
A mutation that helps make cells immortal is critical to the development of a tumor, but new research at the University of California, Berkeley suggests that becoming immortal is a more complicated process than originally ...

New Pathology Atlas maps genes in cancer to accelerate progress in personalized medicine

August 17, 2017
A new Pathology Atlas is launched today with an analysis of all human genes in all major cancers showing the consequence of their corresponding protein levels for overall patient survival. The difference in expression patterns ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.