Reproductive toxicity

One well-known group of substances which are toxic for reproduction are teratogens – substances which cause birth defects. (S)-thalidomide is possibly the most notorious of these. Another group of substances which have received much attention (and prompted some controversy) as possibly toxic for reproduction are the so-called endocrine disruptors.[4] Endocrine disruptors change how hormones are produced and how they interact with their receptors. Endocrine disruptors are classified as estrogenic, anti-estrogenic, androgenic or anti-androgenic. Each category includes pharmaceutical compounds and environmental compounds. Estrogenic or androgenic compounds will cause the same hormonal responses as the sex steroids (estrogen and testosterone). However anti-estrogenic and anti-andogenic compounds bind to a receptor and block the hormones from binding to their receptors, thus preventing their function. A few examples of the many types of endocrine disruptors are trenbolone (androgenic), flutamide (anti-androgenic), dieththylstilbestrol (estrogenic), Bisphenol A (estrogenic), tributyltin (anti-estrogenic). However, many substances which are toxic for reproduction do not fall into any of these groups: lead compounds, for example, are considered to be toxic for reproduction[5][6] given their adverse effects on the normal intellectual and psychomotor development of human babies and children.

Bisphenol A (BPA) is an example of an endocrine disruptor which negatively affects reproductive development. BPA is a known as an estrogen mimicker (Xenoestrogen) and a likely androgen mimicker. It is used in the production of various plastic products. BPA exposure in fetal female rats leads to mammary gland morphogenesis, increased formation of ovarian tumors, and increased risk of developing mammary gland neoplasia in adult life.

BPA also affects male fertility by resulting in lower sperm quality and sex function.

The toxicological impact of BPA is better understood and studied in females than in males.[7][8][9]

Lead is a heavy metal that has been associated not only with mental deficits, but also with male infertility and male reproductive issues. Lead is believed to predominantly affect male reproduction by the disruption of hormones, which reduces the quantity of sperm production in the seminiferous tubules. It has also been proposed that lead causes poor semen quality by increasing reactive oxygen species due to lipid peroxidation, leading to cellular damage.[10][11]

Other reproductive toxins such as Thalidomide were once prescribed therapeutically. In the 1950s and early 1960s, Thalidomide was widely used in Europe as an anti-nausea medication to alleviate morning sickness in pregnant women. But it was found in the 1960s that Thalidomide altered embryo development and led to limb deformities such as thumb absence, underdevelopment of entire limbs, or phocomelia. Thalidomide may have caused teratogenic effects in over 10,000 babies worldwide.[12][13]

Diethylstilbestrol (DES), a synthetic estrogen known to be another reproductive toxin, was used from 1938 to 1971 to prevent spontaneous abortions. DES causes cancer and mutations by producing highly reactive metabolites, also causing DNA adducts to form. Exposure to DES in the womb can cause atypical reproductive tract formation. Specifically, females exposed, in utero, to DES during the first trimester have are more likely to develop clear cell vaginal carcinoma, and males have an increased risk of hypospadias.[14]