Connect with us

NewsMakers

No NELL2, no sperm motility; novel protein is essential for male fertility

Male infertility may arise from lack of communication between the testis and the epididymis and new research has uncovered a mechanism of this communication.

Published

on

Photo by Dainis Graveris from Unsplash.com

Newly produced spermatozoa within the testis are not fully functional until they mature in the epididymis, a duct that helps to transport and store sperm. Male infertility may arise from lack of communication between the testis and the epididymis and new research has uncovered a mechanism of this communication.

Dr. Martin Matzuk at Baylor College of Medicine, Dr. Masahito Ikawa with Osaka University and their colleagues have discovered a novel testicular luminal protein, NELL2, that triggers in the epididymis a chain of events that matures the sperm and enables each one to be motile in females.

Sperm production

Sperm are produced in the seminiferous tubules of the testis and move through the epididymis, a long, convoluted tube linked to the vas deferens, the duct that moves sperm from the testicle to the urethra. When the sperm enter the epididymis, they are not motile and are incapable of fertilization. However, in their passage through the epididymis, the sperm are provided an appropriate environment for maturation and storage pending ejaculation.

It has been hypothesized that proteins released by the testis earlier in this process could act on the epididymis to mature the sperm as they arrive in the epididymis.

“Until now the proteins working through the lumicrine system of signaling have remained elusive. While it was known that the orphan receptor tyrosine kinase ROS1 expressed in the initial segment of the epididymis is necessary for its differentiation, neither the testicular factors that regulate initial segment differentiation nor the process of sperm maturation had been fully understood,” said Matzuk, professor and director of the Center for Drug Discovery at Baylor.

Identifying NELL2

The researchers zeroed in on NELL2, a protein factor secreted by testicular germ cells, as a possible lumicrine regulator of fertility. “Using innovative genome editing technology, we generated knockout mice lacking the NELL2 gene and showed that these knockout males are sterile due to a defect in sperm motility,” explains lead author Dr. Daiji Kiyozum. “Moreover, their infertility could be rescued with a germ-cell-specific transgene, thus excluding other sites of expression. We also illustrated lumicrine signaling by demonstrating tagged NELL2 in the epididymal lumen.”

The research team observed that spermatogenesis proceeds normally in NELL2 knockout mouse testes but their epididymis was poorly differentiated, similar to Ros1 knockout mice. Following mating, neither NELL2 knockout nor Ros1 knockout spermatozoa can enter the uterine tubes or fertilize an egg. Further investigation showed that the Nell2 knockout epididymis is incapable of processing a specific sperm surface protein essential for male fertility.

Implications for male fertility?

Elaborating on their study, Ikawa and Matzuk, both senior authors, said, “We discovered a complicated cascade of events in which disruption of any point in this lumicrine pathway causes a male to be infertile. Our findings have important translational implications for diagnostic and therapeutic research in male infertility and male contraceptive development. This unique transluminal communication pathway between tissues and organs likely functions elsewhere in our bodies.”

Others who contributed to the work include Taichi Noda, Ryo Yamaguchi, Tomohiro Tobita, Takafumi Matsumura, Kentaro Shimada, Mayo Kodani, Takashi Kohda, Yoshitaka Fujihara, Manabu Ozawa, Zhifeng Yu, Gabriella Miklossy, Kurt M. Bohren, Masato Horie and Masaru Okabe.

Zest Magazine accepts contributions promoting everything about living the good life (and how to make this so). C'mon, give us a yell.

NewsMakers

Stress, BMI, and hormones linked to earlier puberty in girls

Higher levels of key steroid hormones—combined with elevated stress and body mass index (BMI)—are associated with earlier onset of puberty in girls.

Published

on

Higher levels of key steroid hormones—combined with elevated stress and body mass index (BMI)—are associated with earlier onset of puberty in girls, according to a new study at Columbia University Mailman School of Public Health.

The findings are published in The Journal of Clinical Endocrinology & Metabolism.

 Elevated prepuberty urinary levels of glucocorticoids, androgens, and progesterone were strongly linked to accelerated breast development (thelarche). Girls with high glucocorticoid levels alongside high BMI and stress entered puberty an average of seven months earlier than peers with lower levels.

“While stress and BMI have long been recognized as independent predictors of puberty, few studies have examined how they interact with a girl’s hormones,” said Lauren Houghton, PhD, assistant professor of Epidemiology at Columbia Mailman School, and first author. “Our findings challenge conventional research that has largely focused on estrogen and body size, highlighting instead the role of stress and androgens – typically thought of as male hormones– in shaping pubescent development.”

The strongest associations were observed for progesterone, androgens, and glucocorticoids, indicating that multiple hormonal pathways—not just estrogen—play a critical role in the timing of puberty.

For example:

  • Higher glucocorticoid, androgen, and progesterone metabolites were associated with earlier onset of puberty
  • Elevated androgens and progesterone were also linked to a longer duration of puberty
  • Estrogen metabolites were associated with delayed onset, not acceleration
  • The effects of hormones on puberty timing were significantly modified by BMI and stress levels.

 Notably, the associations were consistent regardless of family history of breast cancer.

“Our objective was to identify the full set of hormonal patterns linked to accelerated puberty and test whether BMI and stress modify this relationship,” said Houghton, who is also assistant professor at the Herbert Irving Comprehensive Cancer Center at Columbia. “We predicted that girls with elevated BMI and stress would experience the earliest onset—and that the stress response shifts during this key time for girls.”

The researchers drew on data from the LEGACY Girls Study, a cohort of 1,040 girls ages 6 to 13 recruited across the U.S. States and Canada. Participants were followed every six months with clinical assessments, questionnaires, and biospecimen collection.

The analysis included 327 girls who were at the pre-puberty stage at baseline and provided urine samples at least one year before the onset of puberty. Houghton and colleagues measured a comprehensive panel of steroid metabolites using first-morning urine samples and tracked puberty development using validated clinical scales.

Mothers of the girls completed an Internalizing Composite Scale, which includes subscales for anxiety, depression, and other at-risk status. They also provided information on girls’ family history of all cancers as well as on pregnancy and infancy, including birth weight and their child’s race and ethnicity. Trained research staff measured height and weight twice every 6 months. 

“Unlike prior research, this study simultaneously examined hormonal patterns, BMI, and psychosocial stress—captured through standardized behavioral assessments—within the same cohort,” said senior author Mary Beth Terry, PhD, professor of Epidemiology at Columbia Mailman School, and the Herbert Irving Cancer Center, and Silent Spring Institute.  “Interestingly, we also learned that the associations were consistent regardless of family history of breast cancer.”

The findings may help explain the ongoing trend toward earlier puberty and point to actionable prevention strategies, observed the authors.

 “Stress-reducing interventions and healthy lifestyle changes may help delay early puberty and improve long-term health outcomes,” said Houghton. ‘Because early puberty is linked to increased breast cancer risk later in life, the results have important implications for both pediatric care and public health.”

Continue Reading

NewsMakers

Cancer risk is significantly higher for adults who never married, large study finds

Adults who were never married had substantially higher rates of developing cancer compared with those who were or had been married. For some cancers, the association was even stronger: adult men who were never married had approximately five times the rate of anal cancer compared with married men.

Published

on

Adults who have never been married face a significantly higher risk of developing cancer than those who have been married, according to a study of more than 4 million cases.

The increased risk spans nearly every major cancer type and is especially pronounced for preventable cancers—those linked to infections, smoking and reproductive factors. Led by researchers at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, the study appears in the April 8 issue of Cancer Research Communications.

link to the article is here.

“These findings suggest that social factors such as marital status may serve as important markers of cancer risk at the population level,” said Paulo Pinheiro, Ph.D., study co-author and a Sylvester physician-scientist whose lab conducts population-based cancer epidemiology.

The novel observation does not mean that getting married prevents cancer or that people need to get married.

“It means that if you’re not married, you should be paying extra attention to cancer risk factors, getting any screenings you may need, and staying up to date on health care,” said Frank Penedo, Ph.D., associate director for population sciences and director of the Sylvester Survivorship and Supportive Care Institute (SSCI).

“For prevention efforts, our findings point to the importance of targeting cancer risk awareness and prevention strategies with attention to marital status,” he added.

Marriage is already associated with earlier cancer diagnosis and better survival. Married individuals often, but not always, have stronger support systems, greater economic stability and are more likely to adhere to cancer treatment regimens.

But previous work on the links between marriage and cancer focused almost entirely on what happens at and after diagnosis. Only a few small, older studies explored whether marriage affects the odds of getting cancer in the first place.

“We wanted to know who is more likely to get cancer: married people or unmarried people?” Pinheiro said.

To find out, the researchers analyzed a large dataset covering 12 states that included demographic and cancer data from more than 4 million cancer cases in a population of more than 100 million people, collected between 2015 and 2022. They examined cases of malignant cancers diagnosed at age 30 or older and compared rates of various cancers by marital status, further broken down by sex and race and adjusted for age.

The researchers categorized marital status into two groups: those who were or had been married, including married, divorced and widowed individuals, and those who had never been married. The study began in 2015 because that year, the U.S. Supreme Court legalized gay marriage, allowing same-sex couples to be included in the married category. One in five adults in the study had never married.

Pinheiro expected to see some associations, given established relationships between marriage and lifestyle factors such as smoking, routine medical care and having children. But the strength of some findings surprised him.

Adults who were never married had substantially higher rates of developing cancer compared with those who were or had been married. For some cancers, the association was even stronger: adult men who were never married had approximately five times the rate of anal cancer compared with married men. Adult women who were never married had nearly three times the rate of cervical cancer compared with women who were or had been married.

Both anal and cervical cancers are strongly related to HPV infection, so these differences likely reflect variation in exposure, and for cervical cancer, also differences in screening and prevention. In contrast, for cancers such as endometrial and ovarian, differences by marital status may partly reflect the protective effect of parity, which is more common among married individuals.

“It’s a clear and powerful signal that some individuals are at a greater risk,” Penedo said.

Men and women showed slightly different patterns. Men who were never married were about 70% more likely to develop cancer than married men, while women who never married were about 85% more likely to develop cancer than women who were or had been married.

This represents a small but noteworthy reversal of a broader trend: Men often benefit more from marriage than women in terms of health and social factors. In this case, women appeared to benefit slightly more from marriage than men.

The strongest associations between marriage and cancer were seen for cancers related to infection, smoking or alcohol use, and, for women, cancers related to reproduction, such as ovarian and endometrial cancer.

The researchers found weaker associations for cancers with robust screening programs, including breast, thyroid and prostate cancers.

They also observed patterns across race and marital status. Black men who were never married had the highest overall cancer rates. However, married Black men had lower cancer rates than married White men, indicating a strong protective association with marriage in that group.

The study has limitations. People who smoke less, drink less, take better care of themselves and are more socially integrated may also be more likely to get married.

Still, the researchers found that associations between marriage and cancer were stronger in adults older than 50, suggesting that as people age and accumulate cancer risk exposures, the benefits associated with marriage may become more pronounced.

The study also excluded individuals who are unmarried but in committed partnerships. That group is likely small relative to the size of the dataset, Pinheiro said, but worth exploring in future research.

Future studies could further subdivide the married category into married, divorced and widowed individuals and follow people over decades to better understand how marital transitions affect cancer risk.

Overall, getting married does not magically prevent cancer, both authors stressed.

“But the association between marriage status and cancer risk is an interesting, new observation that deserves more research,” Pinheiro said.

Continue Reading

NewsMakers

Social support, sleep, pain management linked to mental health in later life

Older people who are socially connected, physically healthy, and spiritually engaged are significantly more likely to experience complete mental health.

Published

on

Older people who are socially connected, physically healthy, and spiritually engaged are significantly more likely to experience complete mental health.

This is according to a new study, “Flourishing older Canadians: What characteristics are associated with complete mental health?”, that was published in PLOS One.

Using data from 2,024 respondents in Statistics Canada’s 2022 Mental Health and Access to Care Survey (MHACS), researchers examined factors associated with both the absence of psychiatric disorder (APD) and complete mental health (CMH), a broader measure that combines freedom from mental illness with high emotional, psychological, and social well-being.

“Our findings shift the conversation away from mental illness alone and toward understanding what helps older adults truly flourish,” said first author Daniyal Rahim, PhD Candidate, Ontario Institute for Studies in Education, University of Toronto. “Complete mental health reflects not just the absence of disorders, but the presence of meaning, satisfaction, and strong social connections.”

The study found that older adults were more likely to experience APD and CMH if they were married or in a common-law relationship, had strong social support, rated their physical health as fair or better, and reported no chronic pain, sleep problems, or limitations in daily activities. Social support emerged as one of the strongest predictors, more than doubling the odds of achieving complete mental health.

“Social relationships appear to be a cornerstone of mental well-being in later life,” said coauthor Shannon Halls, Research Coordinator, Institute for Life Course & Aging, University of Toronto. “Having people to rely on during stressful times may buffer against psychological distress and promote resilience, happiness, and a sense of purpose.”

Spirituality was also strongly associated with mental well-being. Older adults who reported that religion or spirituality was important in their daily lives had significantly higher odds of both APD and CMH.

“Spiritual beliefs may help older adults cope with adversity by providing meaning, hope, and a sense of community,” said co-author Ying Jiang, a senior epidemiologist in the Applied Research Division, Centre for Surveillance and Applied Research, Public Health Agency of Canada. “These factors can be particularly relevant during periods of declining health or life transitions.”

Physical health factors played a critical role. Freedom from chronic pain, sleep problems, and limitations in instrumental activities of daily living was consistently associated with better mental health outcomes. Conversely, living in a large urban center was linked to lower odds of complete mental health compared to rural living.

“These findings underscore that mental health in aging is shaped by a complex interplay of social, physical, and environmental factors,” said senior author Esme Fuller-Thomson, Director, Institute for Life Course & Aging, University of Toronto, Factor-Inwentash Faculty of Social Work, University of Toronto. “Public health strategies that strengthen social support, address pain and sleep problems, and promote meaningful engagement could substantially improve well-being among older adults.”

The authors emphasize that many of the identified factors are modifiable, suggesting opportunities for targeted interventions, including social programming, pain management, sleep treatment, and community-based supports to help more older Canadians achieve complete mental health.

Continue Reading
Advertisement
Advertisement

Like Us On Facebook

Loading...

Most Popular

Copyright ©FRINGE PUBLISHING. All rights reserved.