ABSTRACT
The female must perform two distinct reproductive functions: development and support of female germ cells, and maintenance of the fetus until it can survive in the outside world. Reproductive toxicology involves detecting and understanding potentially detrimental influences on reproductive success. This field has been developing in response to observations linking clustered effects in humans to specific types of exposure. There are several examples of how xenobiotics in the form of pharmaceuticals can impact reproductive function in humans. One example is the effect of the sedative thalidomide prescribed to women in the 1950s for morning sickness during early pregnancy.1 A greatly increased incidence of children born with developmental organ and limb malformations was traced to in utero exposure to thalidomide. This drug was reported to have been responsible for 8000 malformed children over a 2-year period. Whereas thalidomide is an example involving developmental limb defects, reproductive effects in humans have been seen with the synthetic estrogen diethylstilbestrol (DES). From the 1940s to 1960s, DES was widely prescribed for high-risk pregnancies. In 1971, Herbst et al.2 observed an increased incidence of rare vaginal clear cell adenocarcinoma in daughters of these women who had been exposed in utero to DES. Subsequent research has demonstrated that prenatal exposure to DES can also cause fertility defects, teratogenesis, and neoplasia throughout the male and female reproductive tract.3 Thalidomide and DES represent therapeutic exposures; however, there is also evidence of reproductive effects that have been documented following occupational exposures. In the early 1990s in Korea, a disproportionate number of female workers in an electronics plant who had been exposed to 2-bromopropane (2BP) were discovered to suffer from amenorrhea and hot flashes. Subsequent animal studies have determined that 2BP causes ovarian follicle damage.4 The more recent attention focused on endocrine disruptors has made it clear that there is an incomplete understanding of how xenobiotic chemicals can affect and damage the female reproductive system. With the trend toward women starting families later in life, the effect of longer-term environmental exposure on fertility must be considered. The world has experienced rapid technological and industrial advancement in the last part of the 20th century, making it increasingly important to design and improve approaches for identifying chemicals, drugs, and mixtures that are potentially detrimental to reproductive function in women.
