Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Fetal exposure to two chemicals cause of male reproductive disorders later in life

21.07.2003


Primary author of several recent studies involving di-n-butyl phthalate (DBP) and linuron (L) discusses his findings and what they mean for understanding human development.

Over the last ten years, US researchers have observed a marked increase in some male reproductive disorders, including undescended testicles, increased instances of testicular cancer, and decreased sperm count. In the last 20 years the rates for testicular cancer have grown almost five-fold in Denmark, yet neighboring Finland has not experienced such a dramatic increase. In an effort to explain this phenomenon, scientists have hypothesized that these human male reproductive deficits may have a common origin: a disturbance in the level of androgen and other critical hormones during fetal development. The results from tests with laboratory animals may help scientists better understand the effect of fetal exposure to certain chemicals has on male reproduction abilities later in life.

Paul M.D. Foster, Ph.D., of the National Institutes of Environmental Sciences, Research Triangle Park, NC, and his colleagues have recently co-authored a series of journal articles examining how fetal exposure to two common environmental agents affects the reproductive capabilities of some laboratory animals. Dr. Foster will be discussing their research during a presentation entitled, "Disruption of Male Reproductive Development by Antiandrogens" during the 55th Annual Meeting of the American Association for Clinical Chemistry (AACC), being held at the Pennsylvania Convention Center, Philadelphia, PA, July 20-24, 2003. More than 16,000 attendees are expected.



Background

Dr. Foster and his colleagues have recently published the results of animal studies conducted to explore how two environmental agents, di-n-butyl phthalate (DBP) and linuron (L), can produce a range of reproductive effects in rats, similar to the effects found in humans. Both agents have been related to the incidence of male birth defects at birth and adverse development of male reproduction later in life in rats. The fact that they do so, albeit by differing mechanisms, is likely to help scientists better understand the nature of normal reproductive development.

Di-n-butyl phthalate

DBP is a chemical used as a placticizer and solvent that is in nearly every environmental medium, including air, water, and food. Because it is ubiquitous, some concerns have been raised about its potential health consequences, since one effect of exposure to DBP is that it inhibits the production of androgen, a human male sex hormone. Other effects include malformations of the epididymus, failure of normal testicular descent and malformation of the penis, termed a hypospadias (a condition whereby the urinary tract opening is not located properly at the tip of the penis), a birth defect occurring in every one of 200 male births.

Linuron

Linuron is an herbicide (pesticide) used mainly on soybeans and corn. Because it is sprayed onto crops, a small amount of the chemical is able to incorporate itself into the crop. Unlike DBP, linuron does not decrease the production of androgen, but binds to the androgen receptor to prevent the action of normal androgens. When administered in utero, linuron disturbs the timing of the sequences that must properly take place during fetal development. Linuron interrupts the signals at key times, leading to the development of a variety of birth defects that only affect the male, since it is only the male that requires androgen for their normal reproductive development.

Key Findings

In the studies undertaken by Foster and his colleagues they discovered major malformations, predominantly of the epididymis (an elongated mass of convoluted efferent tubes at the back of the testes), following the administration of the chemicals during critical windows of in utero development (gestation days 12-21). The epididymal malformations were only seen in males after birth.

The series of experiments also found the following:

  • The antiandrogens cause a shortage in testosterone, leading to the various deformities in the fetal male reproductive organs.

  • A leading deformity is malformation of the epididymis, a consequence of the antiandrogens causing direct interference with the fetal reproductive organs and not by interfering with the maternal or fetal endocrine system. The epididymis transports, stores, and matures spermatozoa between the testis and ductus deferens. Blockage of the epididymal structures occurs (similar to a plumbing problem) and leads to infertility and later possible atrophy of the testes.

  • DBP and linuron operate via different mechanisms that affect fetal androgen signaling. The former can lead to failure of the normal development of the reproductive system with malformations in many reproductive organs including hypospadias. (It is noted that hypospadias has shown a significant increase in incidence in the last 20 years and that linuron exposure in the rats led predominantly to a malformation of the epididymis.)

  • The altered adult phenotype following in utero exposure to linuron is very similar to that produced by the antiandrogen DBP, with the exception of testicular lesions and alterations in fetal testosterone levels.

Conclusions

Presently, studies of antiandrogen and the male reproductive system are confined to experimental animals, since human studies exposing pregnant women to large quantities of these chemical agents would be inappropriate. Additionally, common human birth defects are difficult to track and definitively establish cause and effect.

Dr. Foster does not believe that the findings of these animal studies should be cause for alarm. While researchers do not know at what dose level exposure to these chemicals might produce effects in humans, they know that in animals, the dose levels that produce the adverse changes are significantly higher than the levels that have been measured in ongoing human studies.

He does believe that this research, and the similar efforts of other research institutions, will expand the effort to determine how environmental and pharmaceutical antiandrogens may impact on human development. The effects of antiandrogen exposure may not be uniform for any population group. This suggests that research in this field should be linked linked to the ongoing effort to map critical developmental signaling pathways that determine why only some react to these selected agents.

Donna Krupa | EurekAlert!
Further information:
http://www.aacc.org

More articles from Life Sciences:

nachricht Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz

nachricht Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>