SIXTY YEARS LATER....

Salk scientists discover new target for reversible, non-hormonal male birth control

Oral administration of HDAC inhibitor blocked sperm production and fertility in mice without affecting libido

Peer-Reviewed Publication

SALK INSTITUTE

 

IMAGE: 

FROM LEFT: RUTH YU, SUK-HYUN HONG, RONALD EVANS, ANNETTE ATKINS, AND MICHAEL DOWNES

view more 

CREDIT: SALK INSTITUTE

LA JOLLA (February 20, 2024)—Surveys show most men in the United States are interested in using male contraceptives, yet their options remain limited to unreliable condoms or invasive vasectomies. Recent attempts to develop drugs that block sperm production, maturation, or fertilization have had limited success, providing incomplete protection or severe side effects. New approaches to male contraception are needed, but because sperm development is so complex, researchers have struggled to identify parts of the process that can be safely and effectively tinkered with. 

Now, scientists at the Salk Institute have found a new method of interrupting sperm production, which is both non-hormonal and reversible. The study, published in Proceedings of the National Academy of Sciences (PNAS) on February 20, 2024, implicates a new protein complex in regulating gene expression during sperm production. The researchers demonstrate that treating male mice with an existing class of drugs, called HDAC (histone deacetylase) inhibitors, can interrupt the function of this protein complex and block fertility without affecting libido. 

“Most experimental male birth control drugs use a hammer approach to blocking sperm production, but ours is much more subtle,” says senior author Ronald Evans, professor, director of the Gene Expression Laboratory, and March of Dimes Chair in Molecular and Developmental Biology at Salk. “This makes it a promising therapeutic approach, which we hope to see in development for human clinical trials soon.”

The human body produces several million new sperm per day. To do this, sperm stem cells in the testes continuously make more of themselves, until a signal tells them it’s time to turn into sperm—a process called spermatogenesis. This signal comes in the form of retinoic acid, a product of vitamin A. Pulses of retinoic acid bind to retinoic acid receptors in the cells, and when the system is aligned just right, this initiates a complex genetic program that turns the stem cells into mature sperm.

Salk scientists found that for this to work, retinoic acid receptors must bind with a protein called SMRT (silencing mediator of retinoid and thyroid hormone receptors). SMRT then recruits HDACs, and this complex of proteins goes on to synchronize the expression of genes that produce sperm.

Previous groups have tried to stop sperm production by directly blocking retinoic acid or its receptor. But retinoic acid is important to multiple organ systems, so interrupting it throughout the body can lead to various side effects—a reason many previous studies and trials have failed to produce a viable drug. Evans and his colleagues instead asked whether they could modulate one of the molecules downstream of retinoic acid to produce a more targeted effect. 

The researchers first looked at a line of genetically engineered mice that had previously been developed in the lab, in which the SMRT protein was mutated and could no longer bind to retinoic acid receptors. Without this SMRT-retinoic acid receptor interaction, the mice were not able to produce mature sperm. However, they displayed normal testosterone levels and mounting behavior, indicating that their desire to mate was not affected. 

To see whether they could replicate these genetic results with pharmacological intervention, the researchers treated normal mice with MS-275, an oral HDAC inhibitor with FDA breakthrough status. By blocking the activity of the SMRT-retinoic acid receptor-HDAC complex, the drug successfully stopped sperm production without producing obvious side effects. 

Another remarkable thing also happened once the treatment was stopped: Within 60 days of going off the pill, the animals’ fertility was completely restored, and all subsequent offspring were developmentally healthy.

The authors say their strategy of inhibiting molecules downstream of retinoic acid is key to achieving this reversibility.  

Think of retinoic acid and the sperm-producing genes as two dancers in a waltz. Their rhythm and steps need to be coordinated with each other for the dance to work. But if you throw something in that makes the genes miss a step, the two are suddenly out of sync and the dance falls apart. In this case, the HDAC inhibitor causes the genes’ misstep, halting the dance of sperm production. 

However, if the dancer can find its footing and get back in step with its partner, the waltz can resume. In the same way, the authors say that removing the HDAC inhibitor allows the sperm-producing genes to get back in sync with the pulses of retinoic acid, turning sperm production back on as desired. 

“It’s all about timing,” says co-author Michael Downes, a senior staff scientist in Evans’ lab. “When we add the drug, the stem cells fall out of sync with the pulses of retinoic acid, and sperm production is halted, but as soon as we take the drug away, the stem cells can reestablish their coordination with retinoic acid and sperm production will start up again.”

The authors say the drug doesn’t damage the sperm stem cells or their genomic integrity. While the drug was present, the sperm stem cells simply continued regenerating as stem cells, and when the drug was later removed, the cells could regain their ability to differentiate into mature sperm.

“We weren’t necessarily looking to develop male contraceptives when we discovered SMRT and generated this mouse line, but when we saw that their fertility was interrupted, we were able to follow the science and discover a potential therapeutic,” says first author Suk-Hyun Hong, a staff researcher in Evans’ lab. “It’s a great example of how Salk’s foundational biological research can lead to major translational impact.”

Other authors include Glenda Castro, Dan Wang, Russell Nofsinger, Annette R. Atkins, and Ruth T. Yu of Salk, Maureen Kane, Alexandra Folias, and Joseph L. Napoli of UC Berkeley, Paolo Sassone-Corsi of UC Irvine, Dirk G. de Rooij of Utrecht University, and Christopher Liddle of the University of Sydney.

The work was supported by the National Institutes of Health (grants CA265762 and CA220468) and the Next Generation Sequencing and Flow Cytometry Cores at Salk, funded by the Salk Cancer Center (NCI grant NIH-NCI CCSG: P30 014195).

About the Salk Institute for Biological Studies:

Unlocking the secrets of life itself is the driving force behind the Salk Institute. Our team of world-class, award-winning scientists pushes the boundaries of knowledge in areas such as neuroscience, cancer research, aging, immunobiology, plant biology, computational biology, and more. Founded by Jonas Salk, developer of the first safe and effective polio vaccine, the Institute is an independent, nonprofit research organization and architectural landmark: small by choice, intimate by nature, and fearless in the face of any challenge. Learn more at www.salk.edu.

---

JOURNAL

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.2320129121 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Cells

ARTICLE TITLE

Targeting nuclear receptor corepressors for reversible male contraception

ARTICLE PUBLICATION DATE

20-Feb-2024

COI STATEMENT

The authors disclose that the reviewer Dr. Yanhong Shi jointly authored a commentary on an unrelated topic with RME in 2022 (PMID: 35344400).

Generating 'buzz' about new products can influence their success

 NEWS RELEASE 20-FEB-2024

BINGHAMTON UNIVERSITY

 

IMAGE: 

PREANNOUNCEMENT MARKETING CAN OFTEN INFLUENCE A PRODUCT’S SUCCESS, AS IN THE CASE OF THE FILMS "BARBIE" AND "OPPENHEIMER," RESULTING IN THE BARBENHEIMER PHENOMENON.

 

view more 

CREDIT: BINGHAMTON UNIVERSITY, STATE UNIVERSITY OF NEW YORK; UNIVERSAL; WARNER BROTHERS

BINGHAMTON, N.Y. -- The way companies announce new products or build up hype can often influence their success once those new products hit the market, according to new research from Binghamton University, State University of New York. Whether it's an upcoming blockbuster movie or a new rollout from major companies like Coca-Cola or Apple, the new research shows how companies might use this type of preannouncement marketing to their advantage.

How often have you watched trailers for an upcoming movie and thought, “I can’t wait to see that,” when it hits theaters next year?

It’s no surprise when critically acclaimed movies score well at the box office, but when films like “Barbie” or “Oppenheimer” go above and beyond that, the extra push can often be traced back to the buzz they generated building up to their debut on the big screen.

Preannouncement marketing can often influence a product’s success, whether it’s an upcoming blockbuster movie or a new product rollout from major companies like Coca-Cola or Apple. A research study from Binghamton University’s School of Management Associate Professor Debi Mishra shows how companies might use this type of marketing to their advantage.

What these communications provide is another way to think about shareholder return because shareholders want the money that they’re putting in to appreciate in value, said Mishra, a marketing expert who conducted the study. While that often depends on the actual product performance, he said, how companies manage and communicate the “buzz” plays a big role.

“New products are the heartbeat of a company, especially those products that are more consumer-facing, so how a company communicates with consumers or stakeholders about new products is the key to future growth and survival,” Mishra said. “Do you provide all the information upfront or more toward the preannouncement phase? And depending on how this information is communicated, they create surprise in the marketplace that can prove beneficial.”

Mishra and a fellow researcher gauged the impact by collecting data from 149 product launch events and their preceding preannouncements, as reported in The Wall Street Journal from 2005–2018.

By examining what kind of information came out within one year preceding a product’s announcement, whether it was a costly announcement (the company loses money if it doesn’t introduce the product) or a costless one, the researchers could compare the effect on stock across these scenarios.

They found that costless approaches generally resulted in a positive stock market reaction, and contrary to expectations, losses from not investing as much up-front in building up product hype could be compensated after the release. Alternatively, costly approaches didn’t often result in a significant stock market reaction either way.

Examples included:

• The announcement of one new beverage by Coca-Cola didn’t promise when it would be rolled out or how much the company had invested in the new product, meaning it could’ve been easy for the company to reverse that announcement if needed.
• An announcement by IBM to use artificial intelligence to draw insights from digital data and create graphics of data that, while positive, stated it was part of the company’s $1 billion investment.

“If companies create all this buzz about a product but never release it, they might benefit from the stock market having gone up initially, but shareholders will suffer down the road,” Mishra said. “It also makes a difference whether the company makes any kind of guarantee, such as purchasing land worth $20 million for a factory to make the new product. That’s a credible commitment because that money could be lost if they never introduce that product. The market is smart enough to figure these types of things out.”

Mishra said the research also showed a “surprise effect” can impact the market’s reaction to new products.

If a company makes a new product announcement and has already put in a lot of visible commitment behind it, that is no longer a surprise to the market because of an implied expectation the company would follow through with the introduction.

Mishra said a company’s new product announcement that doesn’t provide upfront information about how much is being invested into it could potentially make a larger splash on the market once it comes out.

“If you have something really cool to put out – Brad Pitt is starring in some big upcoming movie – you can’t keep it under wraps all the time, but if your intention is truly honest about introducing that product or movie, it still could be a good idea to keep things somewhat secretive,” Mishra said. “All of a sudden, you’re in the position to have your audience or the market react by saying, ‘Oh, we didn’t expect that!”

The study, "Does the economic value of new product announcements depend upon preannouncement signals? An empirical test of information asymmetry theories," was published in the Journal of Product & Brand Management.

---

JOURNAL

Journal of Product & Brand Management

DOI

10.1108/JPBM-09-2022-4161 

ARTICLE TITLE

Does the economic value of new product announcements depend upon preannouncement signals? An empirical test of information asymmetry theories

 

High persuasiveness of propaganda written by AI

Peer-Reviewed Publication

PNAS NEXUS

 

IMAGE: 

ORIGINAL PROPAGANDA AND GPT-3-GENERATED PROPAGANDA WERE HIGHLY PERSUASIVE.

view more 

CREDIT: GOLDSTEIN ET AL

Research participants who read propaganda generated by the AI large language model GPT-3 davinci were nearly as persuaded as those who read real propaganda from Iran or Russia, according to a study. Josh Goldstein and colleagues identified six articles, likely originating from Iranian or Russian state-aligned covert propaganda campaigns, according to investigative journalists or researchers. These articles made claims about US foreign relations, such as the false claim that Saudi Arabia committed to help fund the US-Mexico border wall or the false claim that the US fabricated reports showing that the Syrian government had used chemical weapons. For each article, the authors used AI to generate new propaganda by feeding one or two sentences from the original propaganda article to GPT-3, along with three other propaganda articles on unrelated topics to use as templates for style and structure. In December 2021, the authors presented the actual propaganda articles and articles generated by GPT-3 to 8,221 US adults, recruited through the survey company Lucid. On average, 24.4% of participants believed the claims without reading any article. Reading a real propaganda article raised that to 47.4%. But reading an article created by GPT-3 was almost as effective: 43.5% of respondents agreed with the claims after reading the AI-generated articles. Many individual AI-written articles were as persuasive as those written by humans. After the survey, participants were informed that the articles contained false information. According to the authors, propagandists could use AI to mass-produce propaganda with minimal effort.

---

JOURNAL

PNAS Nexus

ARTICLE TITLE

How persuasive is AI-generated propaganda?

ARTICLE PUBLICATION DATE

20-Feb-2024

 

SwRI to host second Automotive Corrosion Symposium

Event brings together corrosion experts and automotive industry professionals

Meeting Announcement

SOUTHWEST RESEARCH INSTITUTE

 

IMAGE: 

SOUTHWEST RESEARCH INSTITUTE WILL HOST THE AUTOMOTIVE CORROSION SYMPOSIUM IN DETROIT APRIL 11-12. THE EVENT IS DESIGNED TO FOSTER COMMUNICATION AMONG CORROSION EXPERTS FROM WITHIN AUTOMOTIVE ORIGINAL EQUIPMENT MANUFACTURERS (OEMS) AS WELL AS MATERIAL, PAINT AND OTHER AUTOMOTIVE SUPPLIERS OVER A WIDE SPECTRUM OF INDUSTRY-IDENTIFIED CORROSION ISSUES. SWRI HAS MORE THAN FOUR DECADES OF EXPERIENCE IN CORROSION AND MATERIALS FAILURE RESEARCH. PICTURED IS THE INSTITUTE’S DEDICATED FACILITY FOR COST-EFFICIENT STANDARD CORROSION TESTING.

view more 

CREDIT: SOUTHWEST RESEARCH INSTITUTE

SAN ANTONIO — February 20, 2024 —Southwest Research Institute will host its second Automotive Corrosion Symposium in Detroit April 11-12. The event, first held in 2022, is designed to foster communication among corrosion experts from within automotive original equipment manufacturers (OEMs) as well as material, paint and other automotive suppliers over a wide spectrum of industry-identified corrosion issues.

“Corrosion is a concern within the automotive industry, not just for cosmetic reasons, but because it can affect functionality and safety,” said SwRI Staff Engineer James Dante, one of the organizers of the event. “As the industry is driven toward high-strength, lighter-weight materials with significantly different corrosion properties, this concern is heightened.”

The symposium is organized by industry professionals addressing automotive corrosion from a variety of technical perspectives. This year’s theme is “Applied Corrosion Science for Next-Gen Vehicles.” The organizing committee is accepting abstracts for papers, presentations and posters through February 23. Abstracts can be submitted through the link below.

“The automotive industry is working to reduce emissions as it develops next-generation vehicles,” Dante said. “Whether improving fuel efficiency or pivoting toward electric vehicles, the need for lightweight, strong materials is exploding. These materials must be inherently corrosion-resistant or suitable protection systems are needed to prevent corrosion.”

SwRI has more than four decades of experience in corrosion and materials failure research. A multidisciplinary group of engineers and scientists offer a comprehensive approach to solving corrosion problems for government and industry. The Institute is home to corrosion testing laboratories that characterize materials in a wide array of caustic environments and develop corrosion-resistant materials and coatings to withstand the harshest environments.

For more information or to register to attend the event, visit https://www.swri.org/event/automotive-corrosion-symposium.

 

HPV vaccination among young adults before and during the pandemic

JAMA Network Open

Peer-Reviewed Publication

JAMA NETWORK

About The Study: The results of this study suggest that human papillomavirus (HPV) vaccination coverage among young adults did not increase during the COVID-19 pandemic compared with prior years. This finding likely reflects pandemic-related disruptions in initiating the HPV vaccine among young adults. 

Authors: Kalyani Sonawane, Ph.D., of the Medical University of South Carolina in Charleston, is the corresponding author. 

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/ 

(doi:10.1001/jamanetworkopen.2023.56875)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

#  #  #

Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time http://jamanetwork.com/journals/jamanetworkopen/fullarticle/10.1001/jamanetworkopen.2023.56875?utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_term=022024

About JAMA Network Open: JAMA Network Open is an online-only open access general medical journal from the JAMA Network. On weekdays, the journal publishes peer-reviewed clinical research and commentary in more than 40 medical and health subject areas. Every article is free online from the day of publication. 

---

JOURNAL

JAMA Network Open

Socioeconomically advantaged individuals less likely to seek out HPV vaccination for their children, Hollings researchers find

Peer-Reviewed Publication

MEDICAL UNIVERSITY OF SOUTH CAROLINA

 

IMAGE: 

DR. SONAWANE SAID THAT HPV VACCINE HESITANCY AMONG SOCIOECONOMICALLY ADVANTAGED PARENTS COULD AFFECT AN ENTIRE AGE COHORT. 

view more 

CREDIT: MUSC HOLLINGS CANCER CENTER

The parents of millions of teens have no intention of getting their children vaccinated against the human papillomavirus (HPV). Parents with higher socioeconomic status are less likely than parents of lower income or educational attainment to plan to vaccinate their children.

HPV can cause six types of cancer in both males and females, which is why public health advocates want to see more people vaccinated. The U.S.’s Healthy People 2030 set a goal of 80% of adolescents receiving the full vaccine series, but that rate has stagnated at about 63% for teens.

Researchers from MUSC Hollings Cancer Center, aware of the so-called “reverse disparity,” in which people from low-income or minority communities have better HPV vaccination coverage than people from more advantaged communities, wanted to understand the level of vaccine hesitancy and uncover the reasons that might lead to differences in vaccination coverage. They used the survey results of the National Immunization Survey-Teen, an annual telephone survey that covers several routine adolescent vaccines. Their findings are published this week in The Lancet Regional Health – Americas.

The researchers found that a majority of socioeconomically advantaged parents – 65% – did not intend to seek out the vaccine for their teens, compared with 40% of parents in the disadvantaged group.

The reasons differed by group. Advantaged parents generally cited safety concerns, while disadvantaged parents cited lack of knowledge about the vaccine, lack of recommendation by a primary care provider or the feeling that the vaccine isn’t necessary.

“Parents from socioeconomically advantaged households could be undermining HPV infection risk for their child,” said lead author Kalyani Sonawane, Ph.D., a Hollings researcher and an associate professor in the Department of Public Health Sciences. “The side effects of HPV vaccine are also possibly exaggerated in the minds of parents.”

Senior author Ashish Deshmukh, Ph.D., co-leader of the Cancer Control Research Program at Hollings, noted that white parents, regardless of whether they were advantaged or disadvantaged, showed a “pervasive” lack of intent to vaccinate.

Given that just over half of all adolescents are white, their parents’ vaccination decisions have a significant impact on the herd immunity of the entire age group.

“It has implications at the population level because if most adolescents are white and from middle- or high-income families, and if their parents perceive the vaccine not to be safe, then that impacts vaccine coverage,” Sonawane said.

Previous studies have indicated that minority parents were more likely to accept the vaccine and perceive the threat of HPV infection to be greater. They are not necessarily wrong – Black and Hispanic women have higher rates of both incidence and death from cervical cancer, which is almost always caused by HPV.

At the same time, Deshmukh has published studies over the past year showing that incidence rates of cervical cancer are increasing among white women in low-income counties and among women in their early 30s. Problems accessing preventive care and treatment could be behind the higher death rates of all of these groups.

The HPV vaccine was first approved in 2006. It is recommended for adolescents but can be given as a catch-up vaccine up to age 26. Because HPV is so widespread – the Centers for Disease Control and Prevention notes that nearly everyone will be exposed at some point – the recommendation is to give the vaccine well before one is likely to be exposed. However, after discussion with a doctor, it can be given to adults up to age 45.

There are hundreds of strains of HPV, most of which the human body will clear on its own. Some of those strains, however, can go on to develop into cervical, head and neck, anal, penile, vaginal or vulvar cancer.

Sonawane said that future studies may further subdivide the advantaged group by income or education. This study included a middle group, in which the parents either had less than a high school education or made less than 200% of the federal poverty level. In that mixed group, the researchers found that a higher education level contributed to HPV vaccine hesitancy more than income.

About  MUSC Hollings Cancer Center 

MUSC Hollings Cancer Center is South Carolina’s only National Cancer Institute-designated cancer center with the largest academic-based cancer research program in the state. The cancer center comprises more than 130 faculty cancer scientists and 20 academic departments. It has an annual research funding portfolio of more than $44 million and sponsors more than 200 clinical trials across the state. Dedicated to preventing and reducing the cancer burden statewide, the Hollings Office of Community Outreach and Engagement works with community organizations to bring cancer education and prevention information to affected populations. Hollings offers state-of-the-art cancer screening, diagnostic capabilities, therapies and surgical techniques within its multidisciplinary clinics. Hollings specialists include surgeons, medical oncologists, radiation oncologists, radiologists, pathologists, psychologists and other clinical providers equipped to provide the full range of cancer care. For more information, visit hollingscancercenter.musc.edu. 

---

JOURNAL

The Lancet Regional Health - Americas

DOI

10.1016/j.lana.2024.100694 

ARTICLE TITLE

Factors associated with parental human papillomavirus vaccination intentions among adolescents from socioeconomically advantaged versus deprived households: a nationwide, cross-sectional survey

ARTICLE PUBLICATION DATE

19-Feb-2024

COI STATEMENT

Drs. Sonawane and Deshmukh have provided consultancy to Value Analytics Labs on unrelated projects. Dr. Giuliano received honoraria, and grant funding, and served as a member of the scientific advisory board on unrelated projects for Merck Sharp and Dohme. All other authors declare no competing interests.

 

U$A

Wide variation in rates of police killings suggests unnecessary deaths

PNAS NEXUS

One in three police homicides could have been avoided without endangering police or the public, according to a study. 

Eight percent of all homicides of adult men in the United States are committed by police. 

Using data from 2008–2017 from the National Officer-Involved Homicide Database, Josh Leung-Gagné compared police homicide rates across the 711 local police departments serving 50,000 or more residents in the United States. One explanation for differing rates of police killings is that some jurisdictions are riskier than others, which necessitates more force to keep the public and officers safe. Leung-Gagné compared police homicide rates among departments with similar levels of risk and projected what each department’s rate would have been under average risk conditions, which he quantified using data on violence against officers and officer exposure to violent and other crimes. Leung-Gagné also controlled for differing likelihoods of surviving uses of deadly force, by factoring in access to a trauma care facility. Comparing adjusted rates, Leung-Gagné finds police departments facing similar risks kill at substantially different rates. The deadliest departments kill 6.91 times more frequently than the least deadly departments. If no police departments killed more people than their average peer that faces similar risks, then there would be about a third fewer police homicides overall. Leung-Gagné interprets the data to suggest that at least 1 in 3 police homicides by mid-to-large local police departments are excess police homicides, unnecessary to maintain officer or public safety. According to Leung-Gagné, police homicides can be reduced without reducing officer safety and effectiveness. 

---

JOURNAL

PNAS Nexus

ARTICLE TITLE

The deadliest local police departments kill 6.91 times more frequently than the least deadly departments, net of risk, in the United States

ARTICLE PUBLICATION DATE

20-Feb-2024

 

Even very low levels of pesticide exposure can affect fish for generations, study finds

Peer-Reviewed Publication

OREGON STATE UNIVERSITY

 

IMAGE: 

RESEARCHER SARA HUTTON, A PH.D. GRADUATE OF OSU, EXTRACTS RNA FOR QPCR TO TEST GENE EXPRESSION OF GENES EFFECTED BY PYRETHROID EXPOSURE IN THE DIFFERENT GENERATIONS OF INLAND SILVERSIDE FISH.

view more 

CREDIT: SARA HUTTON

NEWPORT, Ore. — Fish exposed to some pesticides at extremely low concentrations for a brief period of time can demonstrate lasting behavioral changes, with the impact extending to offspring that were never exposed firsthand, a recent study found.

The findings raise concerns not just for fish, but for all vertebrates that are exposed to commonly used pesticides — including humans, said study co-author Susanne Brander, an associate professor and ecotoxicologist in Oregon State University’s Hatfield Marine Science Center.  

“This exposure is happening not just to these fish, but to all aquatic organisms in areas that are receiving runoff from areas populated by humans,” Brander said. “It’s safe to say that we’re seeing influences at the population level if fish that were exposed for a few days as embryos and larvae are then producing offspring that are developmentally deformed, or males that are not able to produce as much sperm.”

Climate change is also expanding the geographic range of many insect species, leading to increased and more widespread pesticide use in both agricultural and residential settings, and increasing the potential for more organisms to be exposed to harmful chemicals.

The study, published in the journal Environmental Science and Technology, used inland silversides as a model fish species common in North American estuaries and marine waterways, with a specific focus on the San Francisco Bay and Sacramento-Joaquin Delta. OSU researchers chose three commonly used pyrethroid pesticides (bifenthrin, cyfluthrin and cyhalothrin) due to their high neurotoxicity and consistent presence in Bay-Delta waters. These pesticides are also widely used and detected nationwide.

For the experiment, researchers exposed silverside embryos to the different pesticides for 96 hours, at a concentration of 1 nanogram of pesticide per liter of water. That’s approximately a teaspoon of pesticide in an Olympic-sized swimming pool, Brander said.

After 96 hours, the fish larvae were placed in clean water and reared until they were five weeks post-hatch. They were then kept in larger tanks until they reached reproductive maturity at about eight months old. At that time, researchers spawned the adult fish and collected their offspring to be reared in clean water. Behavioral responses were measured in larval parents as well as the larval offspring.  

Researchers found the fish that were originally exposed to pesticides demonstrated hypoactive behavior, or decreased activity, at the larval stage, which could lead to them not seeking food as much as the control group, if they were in the wild. Conversely, the second generation of fish — the generation that was never exposed to pesticides, except through their parents — demonstrated hyperactive behavior, swimming more and acting overstimulated compared to the control. Researchers hypothesize this was a compensatory response to the hypoactive behavior of the previous generation.

The tests also found that adult male fish exposed to bifenthrin an cyhalothrin as larvae had smaller gonads than the control group, while the second generation had increased fecundity.

While a lot of research focuses on zebrafish as a model for human health, Brander says many fish species share a large percentage of their genes with humans, and thus can be used as models to predict how humans might respond to a chemical.

“This study is another demonstration of how early-life exposure to these chemicals can affect fish for months and, in the case of humans, for potentially years,” Brander said. “We could potentially use this as a model for how human babies or humans in utero could respond to these chemicals — fish use the same hormone receptors as we do; the same steroids. So something that interferes with reproduction in fish could potentially have the same effect on humans.”

The results showed that the fish were able to adapt in some ways to the exposure, but they might also have been overcompensating, and such changes can come at a cost to success in other biological processes like growth or predation, Brander said.

“In terms of environmental regulation, if we put stricter controls into effect because of studies like this, it’s going to take a few generations of fish — or whatever the organism is — for them to completely recover,” she said.

Lead author on the study was OSU doctoral student Sara Hutton, who graduated last year and now works in environmental consulting. Other co-authors were Samreen Siddiqui, Emily Pederson and Christopher Markgraf at Oregon State; Amelie Segarra and Richard Connon at the University of California, Davis; and Michelle Hladik at the U.S. Geological Survey in California. The study was funded by the Delta Stewardship Council in California.

---

JOURNAL

Environmental Science & Technology

 

Microplastics in every human placenta, new UNM Health Sciences research discovers

Peer-Reviewed Publication

UNIVERSITY OF NEW MEXICO HEALTH SCIENCES CENTER

A flurry of recent studies has found that microplastics are present in virtually everything we consume, from bottled water to meat and plant-based food. Now, University of New Mexico Health Sciences researchers have used a new analytical tool to measure the microplastics present in human placentas.

In a study published February 17 in the journal Toxicological Sciences, a team led by Matthew Campen, PhD, Regents’ Professor in the UNM Department of Pharmaceutical Sciences, reported finding microplastics in all 62 of the placenta samples tested, with concentrations ranging from 6.5 to 790 micrograms per gram of tissue.

Although those numbers may seem small (a microgram is a millionth of a gram), Campen is worried about the health effects of a steadily rising volume of microplastics in the environment.

For toxicologists, “dose makes the poison,” he said. “If the dose keeps going up, we start to worry. If we’re seeing effects on placentas, then all mammalian life on this plant could be impacted. That’s not good.”

In the study, Campen and his team, partnering with colleagues at the Baylor College of Medicine and Oklahoma State University, analyzed donated placenta tissue. In a process called saponification, they chemically treated the samples to “digest” the fat and proteins into a kind of soap.

Then, they spun each sample in an ultracentrifuge, which left a small nugget of plastic at the bottom of a tube. Next, using a technique called pyrolysis, they put the plastic pellet in a metal cup and heated it to 600 degrees Celsius, then captured gas emissions as different types of plastic combusted at specific temperatures.

“The gas emission goes into a mass spectrometer and gives you a specific fingerprint,” Campen said. “It’s really cool.”

The researchers found the most prevalent polymer in placental tissue was polyethylene, which is used to make plastic bags and bottles. It accounted for 54% of the total plastics. Polyvinyl chloride (better known as PVC) and nylon each represented about 10% of the total, with the remainder consisting of nine other polymers.

Marcus Garcia, PharmD, a postdoctoral fellow in Campen’s lab who performed many of the experiments, said that until now, it has been difficult to quantify how much microplastic was present in human tissue. Typically, researchers would simply count the number of particles visible under a microscope, even though some particles are too small to be seen.

With the new analytical method, he said, “We can take it to that next step to be able to adequately quantify it and say, ‘This is how many micrograms or milligrams,’ depending on the plastics that we have.”

Plastic use worldwide has grown exponentially since the early 1950s, producing a metric ton of plastic waste for every person on the planet. About a third of the plastic that has been produced is still in use, but most of the rest has been discarded or sent to landfills, where it starts to break down from exposure to ultraviolet radiation present in sunlight.

“That ends up in groundwater, and sometimes it aerosolizes and ends up in our environment,” Garcia said. “We’re not only getting it from ingestion but also through inhalation as well. It not only affects us as humans, but all off our animals – chickens, livestock – and all of our plants. We’re seeing it in everything.”

Campen points out that many plastics have a long half-life – the amount of time needed for half of a sample to degrade. “So, the half-life of some things is 300 years and the half-life of others is 50 years, but between now and 300 years some of that plastic gets degraded,” he said. “Those microplastics that we’re seeing in the environment are probably 40 or 50 years old.”

While microplastics are already present in our bodies, it is unclear what health effects they might have, if any. Traditionally, plastics have been assumed to be biologically inert, but some microplastics so small they are measured in nanometers – a billionth of a meter – and are capable of crossing cell membranes, he said.

Campen said the growing concentration of microplastics in human tissue might explain puzzling increases in some types of health problems, such as inflammatory bowel disease and colon cancer in people under 50, as well as declining sperm counts.

The concentration of microplastics in placentas is particularly troubling, he said, because the tissue has only been growing for eight months (it starts to form about a month into a pregnancy). “Other organs of your body are accumulating over much longer periods of time.”

Campen and his colleagues are planning further research to answer some of these questions, but in the meantime he is deeply concerned by the growing production of plastics worldwide.

“It’s only getting worse, and the trajectory is it will double every 10 to 15 years,” he said. “So, even if we were to stop it today, in 2050 there will be three times as much plastic in the background as there is now. And we’re not going to stop it today.”

---

JOURNAL

Toxicological Sciences

DOI

10.1093/toxsci/kfae021 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Quantitation and identification of microplastics accumulation in human placental specimens using pyrolysis gas chromatography mass spectrometry

ARTICLE PUBLICATION DATE

17-Feb-2024