Banned stain repellent impacts gene activity key to male fertility, researchers report.

May 05, 2010

Wan, HT, YG Zhao, MH Wong, CKF Lee, WSB Yeung, JP Giesy and CKC Wong. 2011. Testicular signaling is the potential target of perfluorooctanesulfonate-mediated subfertility in male mice. Biology of Reproduction http://dx.doi.org/10.1095/biolreprod.110.089219.

www.biolreprod.org/content/early/2011/01/05/biolreprod.110.089219.full.pdf+html

Synopsis by Brandon Moore

Researchers now better understand how a stain repelling chemical still found in people a decade after its ban impairs hormone and sperm production in adult mice.

An exposure study with adult mice finds that the stain repellant chemical known as PFOS alters expression of key genes that help regulate growth, development and production of several male reproductive functions.

The researchers are the first to identify the specific genes affected by PFOS.  They found the chemical decreased gene activity in the mice testes. The impacted genes, shared by both mice and humans, are critical to the regulation of male fertility, testis growth, testosterone production and sperm maturation. These results start to clarify the specific ways PFOS impacts the mechanisms that guide male reproduction and results in the negative reproductive performance observed in prior human and animal studies. 

Until its almost complete phase-out in the US in 2000 and subsequent ban in the EU,  PFOS was primarily made for use as a textile stain repellent. The organic pollutant does not easily degrade and is now a common contaminant in environments around the world. PFOS also bioaccumulates in the tissues of animals, including humans. Animal experiments and human studies demonstrate PFOS exposure leads to early-life mortality, cancer, immune deficiency and liver and reproductive abnormalities.

While studies of human exposures show decreased male fertility with PFOS exposure, the specific changes in testicular function related to decreased fertility are largely unknown. To understand the connection, the researchers fed sexually mature, eight-month-old male mice 1, 5 or 10 milligrams of PFOS per kilogram of body weight each day (mg/kg/day) for either 7, 14 or 21 days. Body condition, the quality of sperm production and gene expression levels in the testis were measured.

Mice treated for three weeks with the highest PFOS dose had lower body weights, increased liver weights, decreased blood testosterone concentrations and lower sperm counts. These findings agree with the results of previous mouse exposure experiments. The new findings show that the mouse testes also expressed lower levels of genes that  promote testicular maturation and production of male sex hormones.

Similar changes in gene expression were also seen with the lowest dose for 21 days. Notably, the exposure decreased gene expression levels of activin/inhibin subunits and 17-beta-hydroxysteroid dehydrogenase enzyme. Normal expression levels of these genes in testes stimulate development, promote sperm production and perform the last step in the production of testosterone.

These results begin to explain the underlying mechanisms of how PFOS exposure can impact normal testes function that results in the decreased fertility observed in exposed people and lab animals.

 

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