Three proteins may play key roles in female fertility and cancer biology

When a good egg goes bad. The bright green shows spindles, the machinery that helps chromosomes divide. The pink shows one of three key proteins growing out of control after another protein regulator is deleted. The blue shows the chromosomes (DNA). Credit: Alexandra L. Nguyen

Three proteins regulate each other with surprising twists and turns in female mouse eggs, a finding that may play an important role in female fertility and cancer biology, according to Rutgers-led research.

The unexpected complexity in how these proteins regulate one another does not occur in any other healthy cell type, said study senior author Karen Schindler, an associate professor who specializes in infertility research in the Department of Genetics at Rutgers University-New Brunswick.

The three proteins are Aurora kinase A (AURKA), AURKB and AURKC, and the research is published in the journal Current Biology.

"Our research could provide a way to diagnose and perhaps treat certain types of infertility that end in early miscarriage," said Schindler, who works in the School of Arts and Sciences. "This work also impacts cancer biology research because we suspect that the inter-protein regulation that occurs in eggs also occurs in certain types of aggressive cancers. Therefore, the findings could be useful in thinking about precision medicine treatments for cancer patients."

Schindler, an internationally recognized expert in female gamete (egg) biology, said she specializes in infertility research because she's fascinated by the surprisingly high frequency of infertility worldwide. One in six couples struggle to start a family in the U.S. alone, she noted.

The next steps for reproductive biology include studying the genomes of infertile patients to see if mutations in their genes represent a significant percentage of the patient population with poor outcomes in an in vitro fertilization (IVF) clinic, Schindler said. The next steps for cancer biology include carefully evaluating cancers that have all three proteins and finding ways to harness their interactive regulation into a cancer therapeutic.

Scientists at the Academy of Sciences of the Czech Republic and the Spanish National Cancer Research Centre contributed to the study.

 

Source: https://www.sciencedaily.com/releases/2018/10/181025142047.htm

 

Stress reduces fertility in women

image credit: fertilityroad.com

In North America, 20 to 25 percent of women and 18 to 21 percent of men of reproductive age report daily psychological stress. Although previous research has suggested that stress can decrease the odds of conception, few studies have examined this association among couples from the general population.

Now, a new study led by Boston University School of Public Health (BUSPH) researchers finds higher levels of stress are associated with lower odds of conception for women, but not for men.

The study was published in the American Journal of Epidemiology.

"Although this study does not definitely prove that stress causes infertility, it does provide evidence supporting the integration of mental health care in preconception guidance and care," says BUSPH doctoral student Amelia Wesselink, the study's lead author.

The researchers used data from the Pregnancy Study Online (PRESTO), an ongoing preconception cohort of North American pregnancy planners that follows couples for 12 months or until pregnancy, whichever comes first. For the new study, the researchers followed 4,769 women and 1,272 men who did not have a history of infertility and had not been trying to conceive for more than six menstrual cycles.

Removal of ovary for fertility preservation found safe in girls as young as five months

image credit: consultqd.clevelandclinic.org

In the first publication from the U.S. on surgical techniques and outcomes of single ovary removal for fertility preservation in girls, surgeons from Ann & Robert H. Lurie Children's Hospital of Chicago report that the procedure caused no complications and can be performed laparoscopically, on an outpatient basis, without delaying treatment for cancer or other therapies posing high risk of infertility. They present experience with 64 girls, aged 12 years on average, with the youngest only 5 months old at the time of surgery. Their findings were published in the Journal of Pediatric Surgery.

"We describe the unique technical nuances of removing a tiny ovary without damaging it, since it needs to be preserved in the purest form for future transplantation when the patient is ready to pursue pregnancy," says lead author Erin Rowell, MD, Director of the Fertility and Hormone Preservation and Restoration Program at Lurie Children's and Associate Professor of Surgery at Northwestern University Feinberg School of Medicine.

Women who breastfeed for at least five months have more kids

image credit: sciencenews.org

Women who breastfeed their first child for five months or longer are more likely to have three or more children, and less likely to have only one child, than women who breastfeed for shorter durations or not at all.

In "Intensive Parenting: Fertility and Breastfeeding Duration in the United States," published in the journal Demography, Cornell University professor of sociology Vida Maralani, with Hunter College professor Samuel Stabler, reports that women who initiate breastfeeding did not differ in how many children they expected to have before they started their families. Rather, the number of children women actually bear differs by how long they breastfeed their first child. Women who breastfeed for shorter durations are more likely to have fewer children than they expected, while women who breastfeed longer are as likely to achieve their expectations as to exceed them.

The researchers caution that their results do not imply that breastfeeding duration causes women to have larger families. They write, "Our study reveals the opposite: the interconnectedness of family preferences and child investment across the life course." But they do find that many factors, such as differences in education, marital status, family income, and working for pay do not explain these patterns. The authors point to the need to study other potential explanations such as spousal support, preferences for time spent with children or work flexibility.

Does Eating Organic Really Matter to Fertility?

healthline.com

Recent pesticide research related to the Environment and Reproductive Health Study (EARTH) was published in JAMA Internal Medicine on Oct 30, 2017. Scientists at Harvard T.H. Chan School of Public Health (Yu-Han Chiu and Jorge Chavarro, MD) evaluated pesticide exposure from the dietary fruit and vegetable intake of 325 women in fertility treatment at Massachusetts General Hospital.

Study results found that men and women who ate more than two servings daily of fruits or vegetables with high pesticide content were 26% less likely to have a live birth than those with the lowest pesticide exposure. The data did not show any pesticide association with fertilization or embryo implantation concerns but did associate with an increased risk of miscarriages early in pregnancy.

To stay fertile, eggs demand food via food tubes

New research clarifies how female reproductive cells—eggs or oocytes—get the food they need to grow and remain fertile.

The egg gets its food from little arm-like feeding tubes (called filopodia) that jut out from tiny cells surrounding the egg and must poke through a thick wall coating the egg in order to feed it. Until recently, scientists did not really understand the place and timing of the feeding tubes’ construction.

It turns out the egg is in charge and its communication skills are highly sophisticated. When it’s time to get food, the egg sends signals to the tiny surrounding cells to make the feeding tubes, and as it grows and needs more nourishment, it signals them to make even more tubes.

These findings, which push the scope of our understanding of female fertility, appear in Current Biology.

The study, conducted in mice, reveals that growth factors—especially one known as growth differentiation factor 9—coming from the eggs drove the feeding tube multiplication and growth process, acting directly upon the genetic machinery of the follicle cells surrounding the egg. These discoveries put the spotlight directly on the egg itself, says Hugh Clarke, who led the research team at the Research Institute of the McGill University Health Centre.

“It shows that the egg is playing an active role in creating the microenvironment that it needs to continue its development,” says Clarke, lead study author, who is also a senior scientist from the Child Health and Human Development Program at the RI-MUHC and a professor and research director of the department of obstetrics and gynecology at McGill University.

“We observed that the whole process of egg development and its interaction with its environment is not static. It’s very dynamic,” adds first study author Stephany El-Hayek, who was a PhD student in Clarke’s lab at the time of the work.

The team also found that in older mice, the cells surrounding the egg produced fewer feeding tubes. Scientists know that the eggs of older women are less successful in producing healthy babies, but they don’t know the reason why. Clarke’s research offers a new possible explanation.

Might it be because the cells surrounding the egg are not good at making enough feeding tubes as the egg grows older? The answer to that question, which Clarke’s team is now investigating, could one day lead to the possibility of increasing fertility or even retaining fertility longer into older age, he says.

“Understanding how the egg interacts with its environment will allow us to ensure that growing eggs retain their fertility,” says Clarke. “But it could also lead to developing techniques to grow healthy eggs in the laboratory in an effort to preserve fertility in women who have cancer,” says Clarke.

Source: futurity.org

Micronutrient availability can have early and long-lasting effects on egg quality

sciencemag.org

An estimated 10 percent of couples in the U.S. struggle with infertility. While a variety of factors can make it difficult for some people to get pregnant, ovulation disorders are a leading cause of female infertility. Now, researchers at Pennsylvania State University have found that zinc deficiency can negatively affect the early stages of egg development, reducing the ability of the egg cells to divide and be fertilized. This may affect fertility months in the future. The researchers will present their results at the American Physiological Society annual meeting at Experimental Biology 2018 in San Diego.

The availability of micronutrients in the ovarian environment and their influence on the development, viability and quality of egg cells (oocytes) is the focus of a growing area of research. In mammals, the ovary is made up of thousands of structures called follicles -- women are born with approximately two million -- which consist of one oocyte surrounded by layers of support cells (somatic cells).

After puberty, a complex cascade of events occurs to prepare groups of oocytes for maturation, ovulation and fertilization. Though a group of oocytes begins to mature each month, only one will be ovulated and have the chance of being fertilized. Multiple factors can influence whether a given oocyte will mature correctly and one day be ovulated, including the presence of sufficient levels of certain micronutrients.

New clues to restoring fertility in women with disabling ovary disorder

via yabibo.com

Findings from the research, conducted in a pre-clinical model and just published in the Journal of Clinical Investigation Insight, show that blocking androgen actions could help re-set reproductive function to normal levels by modifying brain circuitry important to fertility.

Associate Professor Rebecca Campbell from the University's Centre for Neuroendocrinology and Department of Physiology, says she and her co-investigators, Ph.D. student Mauro Silva and Assistant Research Fellow Mel Prescott, are excited about their findings which are potentially significant for women suffering from the syndrome.

"Our findings suggest that despite the early development of brain pathology in some forms of polycystic ovary syndrome, normal reproductive function can potentially be restored in adult women with the disorder through modifying the wiring in the brain," Associate Professor Campbell explains.

There is growing evidence the brain is involved in both the development and pathology of polycystic ovary syndrome. The Otago researchers' earlier work in a preclinical model on the syndrome has identified changes in specific brain circuits that may underlie the disorder.

In this most recent study, Associate Professor Campbell and her team investigated when these circuit abnormalities develop and whether the circuits are "hard-wired" or can be changed by blocking androgen actions once the disorder is established.

"We discovered that brain changes occur prior to the onset of puberty, which is before the syndrome appears, suggesting that the brain pathology precedes disease development," Associate Professor Campbell says.

"We also discovered that, despite this early 'programming' of neural circuitry, long-term blockade of androgen actions was able to completely restore normal brain wiring and reproductive cycles."

Associate Professor Campbell says that although the work is still pre-clinical, it gives clues about potentially effective therapies in treating the reproductive pathology of polycystic ovary syndrome in women.

Her research team has established a collaboration with clinicians in Sweden to retrospectively look at the impact of androgen receptor blocker drugs on long-term reproductive outcomes in women with the syndrome. 

 

Source: https://medicalxpress.com/news/2018-04-clues-fertility-women-disabling-ovary.html

 

More care needed in warnings about fertility in eating disorder treatment

image credit: mindbodypregnancy.com

"Women in treatment for eating disorders need more nuanced information about reproductive health, and more thought needs to be given to how and why fertility information is delivered, according to new research from the University of East Anglia (UEA).

That's part of an overall set of findings that suggest those with eating disorders (EDs) should have more input into their treatment and how medical information is communicated. The research, 'Responses to warnings about the impact of eating disorders on fertility: A qualitative study', is published today in Sociology of Health and Illness. The research was led by Dr Su Holmes, a reader in UEA's School of Art, Media and American Studies.

Dr Holmes said: "Medical intervention does not recognise the complexities of the individual causes of ED, nor are treatment options delivered on a case-by-case basis. Invariably, treatment regimes look at EDs as a 'problem' to be solved, rather than considering the myriad reasons the individual may be in eating distress or body distress."

Nowhere is this more evident than when it comes to medical professionals discussing reproductive health with women in treatment, said Dr Holmes. Not only is the empirical evidence that EDs pose a risk to fertility contradictory, she said, but if delivered as a 'warning', medical advice about a possible link between EDs and infertility presents further problems..." 

Learn more:https://www.sciencedaily.com/releases/2018/02/180221204935.htm

Underactive thyroid within normal range may affect woman's ability to conceive

via arcfertility.com

"New research suggests that a slightly underactive thyroid may affect a women's ability to become pregnant -- even when the gland is functioning at the low end of the normal range, according to a study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.

The study found women who have unexplained infertility were nearly twice as likely to have higher levels of a hormone that stimulates the thyroid gland than women who did not conceive due to known issues with their male partner's sperm count. Thyroid-stimulating hormone (TSH) is produced by the pituitary gland at the base of the brain and tells the thyroid gland to produce more hormones when needed. Elevated TSH levels can be a sign that the thyroid gland is underactive.

Unexplained infertility occurs when couples are unable to get pregnant despite months of trying and a medical evaluation shows no reason for their infertility. About 10 percent of American women between the ages of 15 and 44 have difficulty becoming or staying pregnant, according to the Office of Women's Health in the U.S. Department of Health and Human Services. Between 10 percent and 30 percent of affected couples have unexplained infertility, according to the JCEM study.

"When couples who are ready to start a family are unable to conceive despite extensive planning, multiple doctor's visits, and expensive treatments, it can be emotionally devastating," said the study's senior author, Pouneh K. Fazeli, M.D., M.P.H., of Massachusetts General Hospital and Harvard Medical School in Boston, Mass. "Since our study shows that women with unexplained infertility have higher TSH levels compared to women experiencing infertility due to a known cause, more research is needed to determine whether treating these higher TSH levels with thyroid hormone can improve their chances of getting pregnant..."

Learn more:

https://www.sciencedaily.com/releases/2017/12/171219144412.htm

Estrogen discovery could shed new light on fertility problems

via fineartamerica.com

"Estrogen produced in the brain is necessary for ovulation in monkeys, according to researchers at the University of Wisconsin-Madison who have upended the traditional understanding of the hormonal cascade that leads to release of an egg from the ovaries.

Their findings, published Dec. 11 in the journal Proceedings of the National Academy of Science, may reveal the cause of some undiagnosed infertility problems and point the way to new methods of birth control.

For decades, scientists have known that a group of neurons in a part of the brain called the hypothalamus and cells in the pituitary gland control the menstrual cycle. The brain stimulates the pituitary to make hormones that, early in the menstrual cycle, spur the ovaries to produce estrogens -- predominantly a type of estrogen called estradiol.

Estradiol builds in the bloodstream until it reaches a concentration that causes a surge of the hypothalamic and pituitary hormones, including one called luteinizing hormone, which in turn trigger an ovary to release an egg.

"It's a feedback loop, and scientists have thought for some time that it was all to do with the estrogen from the ovaries," says Ei Terasawa, professor of pediatrics at the UW-Madison School of Medicine and Public Health and senior scientist at the Wisconsin National Primate Research Center. "Then, in 2013, we discovered the hypothalamus was releasing estradiol like the ovaries, and we were so surprised. We knew it had to be important..."

Learn more:

https://www.sciencedaily.com/releases/2017/12/171212124725.htm

A common periodontal pathogen may delay conception in young women

image credit: fitpregnancy.com

"According to a study carried out at the University of Helsinki, Finland, a common periodontal pathogen may delay conception in young women. This finding is novel: previous studies have shown that periodontal diseases may be a risk for general health, but no data on the influence of periodontal bacteria on conception or becoming pregnant have been available.

"Our results encourage young women of fertile age to take care of their oral health and attend periodontal evaluations regularly," says periodontist and researcher Susanna Paju, University of Helsinki.

Study population comprised 256 healthy non-pregnant women (mean age 29.2 years, range 19 to 42) who had discontinued contraception in order to become pregnant. They were enrolled from the general community from Southern Finland. Clinical oral and gynecological examinations were performed. Detection of major periodontal pathogens in saliva and analysis of serum and saliva antibodies against major periodontal pathogens as well as a vaginal swab for the diagnosis of bacterial vaginosis at baseline were carried out.

Subjects were followed-up to establish whether they did or did not become pregnant during the observation period of 12 months.

Porphyromonas gingivalis, a bacterium associated with periodontal diseases, was significantly more frequently detected in the saliva among women who did not become pregnant during the one-year follow-up period than among those who did. The levels of salivary and serum antibodies against this pathogen were also significantly higher in women who did not become pregnant..."

Learn more: 

https://www.sciencedaily.com/releases/2017/06/170612153549.htm

Why fertility declines with age?

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"Researchers at the University of Montreal Hospital Research Center (CRCHUM) have discovered a possible new explanation for female infertility. Thanks to cutting-edge microscopy techniques, they observed for the first time a specific defect in the eggs of older mice. This defect may also be found in the eggs of older women. The choreography of cell division goes awry, and causes errors in the sharing of chromosomes. These unprecedented observations are being published today in Current Biology.

"We found that the microtubules that orchestrate chromosome segregation during cell division behave abnormally in older eggs. Instead of assembling a spindle in a controlled symmetrical fashion, the microtubules go in all directions. The altered movement of the microtubules apparently contributes to errors in chromosome segregation, and so represents a new explanation for age-related infertility," stated CRCHUM researcher and Université de Montréal professor Greg FitzHarris.

Women -- and other female mammals -- are born with a fixed number of eggs, which remain dormant in the ovaries until the release of a single egg per menstrual cycle. But for women, fertility declines significantly at around the age of 35.

"One of the main causes of female infertility is a defect in the eggs that causes them to have an abnormal number of chromosomes. These so-called aneuploid eggs become increasingly prevalent as a woman ages. This is a key reason that older women have trouble getting pregnant and having full-term pregnancies. It is also known that these defective eggs increase the risk of miscarriage and can cause Down's syndrome in full-term babies" explained FitzHarris..."

Learn more:

https://www.sciencedaily.com/releases/2017/04/170403123542.htm

Gene WT1 impacts women's fertility

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"It has been estimated that more than 80 million people in the world have an unfulfilled desire to have children. But for every 10th couple, the reasons therefor remain unclear. Now, researchers from the Leibniz Institute on Aging (FLI) in Jena/Germany have, together with clinical partners, found a new gene mutation that obviously leads to infertility in women. 

The mutated gene WT1 plays an important role in the early embryonic development controlling proteins (especially proteases) that are needed for the successful nidation in mother's womb. The astonishing results were recently published in the journal Human Molecular Genetics.

For many couples, starting an own family remains an unfulfilled dream. According to estimations, this is true for about 80 million people worldwide. Some fight for years to have own children; some stay childless without any medical indication. Now, researchers from Leibniz Institute on Aging -- Fritz Lipmann Institute (FLI) in Jena/Germany in collaboration with clinical partners discovered a formerly unknown gene mutation that could at least partly explain unwanted childlessness. The study's results were recently published in the journal Human Molecular Genetics.

Newly discovered mutation of gene WT1

In collaboration with the Sophien and Hufeland Hospital Weimar and the Heidelberg University Women's Hospital, researchers from FLI's research group of Christoph Englert investigated samples of women younger than 40 years that suffer from unwanted childlessness. In one out of eight women, the gene WT1 showed a previously unknown mutation in one of its two alleles. "This result was really surprising," explains Dr. Abinaya Nathan, who is the study's first author. "Up to now, WT1 was only known as tumor suppressor gene important for the development and maintenance of organs like heart or kidney." But which role does this gene play with regard to fertility?..."

Learn more:

https://www.sciencedaily.com/releases/2017/03/170328095304.htm

Is female fertility affected by physically demanding jobs and shiftwork?

via the journal.ie

"A physically demanding job or work schedules outside normal office hours may lower a woman's ability to conceive, suggests research published online in Occupational & Environmental Medicine.

Heavy lifting at work and evening/night/rotating shift patterns were associated with poorer egg quality, the findings show.

Previous research has linked occupational factors to fertility, measured in outcomes such as time to pregnancy and the ability to carry a pregnancy to term. But no study has assessed whether workplace factors might affect a woman's biological capacity to have a baby.

To try and address this, the research team looked at indicators of 'ovarian reserve' -- the number of remaining eggs (antral follicle count) and levels of follicle stimulating hormone or FSH for short, which rise as a woman ages and represent dwindling fertility -- in 473 women attending one fertility clinic.

And they also looked at ovarian response -- the number of mature eggs capable of developing into a healthy embryo in 313 of the women who had completed at least one cycle of IVF by December 2015..." 

Learn more:

https://www.sciencedaily.com/releases/2017/02/170207191851.htm

High alcohol intake associated with slightly decreased female fertility

via preventionconversation.org

"Women who drink 14 or more servings of alcohol a week are slightly more likely to have reduced fertility, suggests a study published by The BMJ today.

Low to moderate intake of alcohol, defined as one to seven servings a week, seemed to have no effect on women's fertility, nor did the type of alcohol beverage consumed.

But the authors still recommend for couples to abstain from alcohol during their fertile window until a pregnancy is ruled out, because the fetus may be particularly vulnerable to alcohol during the first few weeks after conception.

In developed countries, up to 24% of couples experience infertility, defined as time to pregnancy of 12 months or more.

Official guidelines in several countries, including the UK, USA and Denmark, recommend that women trying to become pregnant should abstain from alcohol consumption. But the extent to which alcohol intake affects female fertility is unclear..."

Learn More:

https://www.sciencedaily.com/releases/2016/08/160831223734.htm

How females store sperm

via healthland.time.com

Source:Hiroshima University | Summary: The science of breeding chickens has revealed part of the mystery of how certain female animals are able to store sperm long-term. Droplets of fat transferred from female cells to sperm cells may contribute to keeping sperm alive. A scientific understanding of how sperm can be kept viable longer could benefit any fertility-related work.

"The science of breeding chickens has revealed part of the mystery of how certain female animals are able to store sperm long-term. Droplets of fat transferred from female cells to sperm cells may contribute to keeping sperm alive.

Females of some types of insects, reptiles, and birds can store sperm from multiple males within specialized sperm storage areas of their reproductive tracts. Different animals can store sperm for days or years. Stored sperm can fertilize multiple eggs over time, meaning females do not need to mate again to fertilize additional eggs.

"Farmers may be able to more successfully breed their flocks if we could understand how the sperm stays viable in the sperm storage tubules of female chickens. Fertility studies like this are especially relevant to countries that breed native chickens with lower reproductive rates," said Yukinori Yoshimura, Ph.D., leader of the Research Center for Animal Science and Professor in the Graduate School of Biosphere Science at Hiroshima University.

Yoshimura led the research team that identified five types of lipid, or fatty acids, that exist as droplets inside the cells of female chickens' sperm storage tubules. After the chickens were artificially inseminated, a gene responsible for breaking down those lipids became 2.5 times more active. These broken-down lipids may be released into the sperm storage tubules and improve the sperm's survival..."

Learn more:

https://www.sciencedaily.com/releases/2016/06/160613102430.htm

Female fertility is dependent on functional expression of the E3 ubiquitin ligase Itch

Source: Society for Experimental Biology and Medicine | Summary: Protein ubiquitination is known to result in its proteasomal degradation or to serve as a signal for tissue-specific cellular functions. Here it is reported that mice with a mutant form of the E3 ubiquitin ligase ITCH display reduced litter sizes due to a maternal effect. Mutant females had decreased numbers of implantations, corpa lutea, and extended estrous cycles. The results indicate for the first time that loss of functional ITCH disrupts female reproduction.

"The post-translational addition of ubiquitin to proteins by enzymes of the E3 ubiquitin ligase family is largely recognized as a means to target misfolded or unwanted proteins for degradation by the proteasome. 

However, it is now understood that ubiquitination serves as a signal to modify a number of cellular functions such as protein trafficking, cell signaling, DNA repair, chromatin modifications, cell-cycle progression, and cell death. 

Though these functions are integral for all cells throughout the body, the physiologic role of specific E3 ligases must yet be defined in the context of various tissues. For example, very few studies exist that interrogate the function of specific E3 ubiquitin ligases in the reproductive system..."

Read the rest of the article here:
https://www.sciencedaily.com/releases/2016/02/160229182656.htm