December 2007, Vol. 13, No. 3

Focus on: Endocrine Disruptors
Phthalates Toxic to Testosterone-Producing Cells

A recent scientific review authored by Population Council biomedical researchers has detailed the ways that chemical plasticizers damage the testosterone-producing Leydig cells. These chemicals, known as phthalates, are added to plastics to increase their flexibility. Phthalates are found in products as diverse as children’s toys, medical tubing, and shampoo bottles. These findings have numerous implications for male fertility and health.

The review was written by Population Council biomedical researchers Matthew P. Hardy, Ren-Shan Ge, and Cigdem Tanrikut, along with Guo-Rong Chen of China’s Wenzhou Medical College, and appeared in the journal Reproductive Toxicology. A related article appeared in the Chinese-language National Journal of Andrology.  

Testicular dysgenesis syndrome
Research from Hardy’s lab, as well as findings from other labs around the world, shows that phthalates exert a negative influence on Leydig cells, disrupting testosterone production and increasing cell proliferation. These effects potentially contribute to testicular dysgenesis syndrome. This syndrome includes a variety of conditions that involve the male reproductive system, including undescended testes, hypospadias (an abnormality of the penis in which the urethra opens on the underside), changes in the timing of puberty, testicular cancer, and reduced fertility. These various disorders have been hypothesized to arise from the same underlying condition, an injury or trauma to testicular development that occurs before birth. This trauma results in a failure to develop normal Leydig and Sertoli cells, two of the main cells that make up the testes. Leydig cells produce testosterone, and Sertoli cells nurture developing sperm cells. Hardy’s lab deals primarily with Leydig cells.

Studies by Hardy and others have shown that phthalates can affect Leydig cells in complicated ways at every stage of their development. Phthalates disrupt the production by Leydig cells of both testosterone and insulin-like growth factor 3 (INSL3). Phthalate interference with these substances could result in undescended testes. “The binding of INSL3 with a specific receptor, together with testosterone, is the trigger that causes the testes to descend from inside the abdomen, where they developed during gestation, to the scrotum outside the body,” explains Ren-Shan Ge, a biologist in the Hardy lab and author on the recent study. The disturbance of testosterone production by phthalates could also lead to impaired sperm production.

In their recent summary, the Hardy team states that their studies, and studies from other laboratories, are building an evidence base showing that phthalates do not disrupt the endocrine, or hormonal, system by binding to hormone receptors, which is the way that many other endocrine disruptors operate. Phthalates instead seem to “alter reproductive function by affecting hormone synthesis,” according to Hardy and his co-authors. In many cases, screening assays that detect interference with hormone receptors have been used to evaluate potential endocrine disruptors. However, the team concludes, alternative tests may be needed in the case of phthalates.

Sources
Chen, Guo-Rong, L. Dong, Ren-Shan Ge, and Matthew P. Hardy. 2007. “Relationship between phthalates and testicular dysgenesis syndrome,” National Journal of Andrology 13(3): 195–200.

Ge, Ren-Shan, Guo-Rong Chen, Cigdem Tanrikut, and Matthew P. Hardy. 2007. “Phthalate ester toxicity in Leydig cells: Developmental timing and dosage considerations,” Reproductive Toxicology 23(3): 366–373.

Outside funding
The Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust and the National Institute of Environmental Health Science of the U.S. National Institutes of Health

(Return to issue contents)

---

Related Project

• Action of Endocrine Disrupters on Leydig Cells

See Also

• "Low chemical exposure may speed male puberty," Population Briefs 11(3): 2.
  (full text)

---