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Endocrine Disruptors and Reproductive Function - Is Your Water Bottle Making You Infertile?

Posted Mar 16 2010 12:00am
By: Ervin E. Jones, PhD, MD, FACOG

The term "Endocrine Disruptor" is use to describe a class of chemicals that act as agonists or antagonists of estrogens, androgens and thyroid hormones. The term has evolved to encompass hundreds of chemicals. Endocrine disruptors are foreign substances that perturb normal endocrine processes by mimicking the activity of natural hormones and, thereby, disrupt the synthesis, metabolism and functions of natural hormones.

Xenoestrogens as Endocrine Disruptors

The prefix "xeno" is derived from the Greek word "xenos" which means stranger or foreign. Thus, xenoestrogens are, by definition, estrogens that are foreign to the body. Included among the xenoestrogens discussed here are phthalates, bisphenols, organotins, phytoestrogens and diethylstilbesterol. Phthalates are compounds used in a wide variety of consumer products including plastics, adhesives, deforming agents, solvents, lubricants, vinyl upholstery, table cloths, shower curtains, rain coats, personal care products and children's toys. Phthalates are also used in some approved medical devices such as tubing, blood packs and dialysis equipment as well as surgical gloves. Globally, more than 18 billion pounds of phthalates are used each year. Phthalates can readily leach out of plastics since they are not chemically bound to the plastic matrix. Because of their widespread use in consumer products, phthalates are widely distributed in the environment and their potential for incorporation by oral, dermal, inhalation and intravenous means is high.

Bisphenols are organic compounds made by condensing acetone with phenol. Bisphenols are also widely used in plastics and plastic additives. One cross sectional study found bisphenols in 92.6 percent of the United States population examined. Organotins are compounds that contain tin linked to hydrocarbons. Organotins represent another class of widespread persistent organic pollutants with potent endocrine disrupting properties. Organotins are also used in polyvinyl chloride products as stabilizers and, therefore, may come in contact with packaged food products. Organotins bind to receptors that play key roles in fat homeostasis and adipogenesis and are, therefore, potent endocrine disruptors.

Although synthetic chemicals have received the most attention as endocrine disruptors in recent years, substances produced in nature may also function as endocrine disruptors. A notable example is the group of plant hormones known as phytoestrogens. Certain plant hormones are xenoestrogens and are found in many foods such as soy and food supplements. Diethylstilbesterol (DES) was the first recognized and only clearly documented xenoestrogens clearly linked to human disease. The synthetic estrogen was administered to pregnant women in the 1950s and 1960s to prevent miscarriage. DES was implicated in urogenital abnormalities in children exposed in utero and was withdrawn from the market in 1971. Girls exposed to DES showed a high incidence of vaginal abnormalities, spontaneous abortion, premature delivery, uterine malformation, menstrual abnormalities and low fertility. Boys exposed to DES showed Testicular Disgenesis Syndrome which is characterized by hypospadias (posterior displacement of the urethral opening on the penile shaft), undescended testes and low semen quality.

Endocrine Disruptors and Male Reproduction

According to some epidemiological studies the quantity and quality of human sperm has decreased during the last 60 years. In humans, although the causes are not clear, hypospadias has doubled from 1970. Sperm counts decreased and testicular cancer incidence increased. Global declines in semen quality were suggested to be associated with enhanced exposure to environmental chemicals that act as endocrine disruptors as a result of our increased use of pesticides, plastics, and other materials. Adult men exposed to certain phthalate esters were found to have lower levels of testosterone when compared to unexposed controls. Studies using animal tissues support these observations. In utero exposure of rats to the phthalates resulted in dose -dependent decreases in testosterone production in testis tissue obtained from adult rats.

Endocrine Disruptors and Female Reproduction

Recent epidemiologic evidence suggests that women have a unique exposure profile to phthalates. These high levels may be due to the fact that certain phthalate derivatives are used in many beauty products including perfumes, lotions, and nail polish. A study reported by the Centers for Disease Control found that reproductive age women had significantly higher concentrations of phthalate esters in their urine when compared with age- and sex-matched controls. Exposure to high levels of phthalates is associated with decreased pregnancy rates and higher miscarriage rates in female factory workers. Ovarian intrafollicular processes may be targets for environmental endocrine disruptors. Recent studies using animal models have shown that certain phthalates disrupt follicle stimulating hormone induced cumulus cell expansion, oocyte maturation in vitro and alters progesterone production in animal models. An increase in aneuploidy was found coincident with abnormal alignment of chromosomes on the meiotic spindle.

Cells obtained from human ovarian follicles during IVF procedures are steroidogenically active and respond to FSH and LH stimulation. Phthalates disrupted estradiol and progesterone production in these cells, suggesting that certain phthalate derivatives act as specific inhibitors of estradiol production in human granulosa cells. As the in vitro effective doses of the compound were within the range of real environmental exposure levels an inhibitory effect of estrogen production in vivo seems possible.

Obesity has become a global health crisis. Several studies have highlighted the link between obesity and infertility. Obesity contributes to anovulation and menstrual irregularities, reduced conception rates, reduced response to fertility treatment and to increased rates of miscarriage. A set of candidate endocrine disruptors referred to as obesogens (diethylstilbestrol, bisphenol A, phthalates and organotins among others have been proposed. These putative obesogens bind to receptors that play key roles in fat homeostasis and the genesis of adipose tissue. Evidence points to endocrine disrupting chemicals that interfere with the body's adipose tissue biology and endocrine systems to derail the mechanisms essential to weight control. Implantation pregnancy and live birth rates were poor in obese women. Pregnancy and live birth rates were reduced progressively as weight increased. Pregnancy rates in overweight women were approximately half those of normal women.

Conclusions

Endocrine disruptors are natural or synthetic compounds that perturb certain normal endocrine functions Taken together, the key deficits that appear to be imposed on fertility by environmental endocrine disruptors include abnormalities of hormone production, egg maturation and maintenance of pregnancy. Although somewhat controversial and inconclusive, the findings indicating adverse effects of endocrine disruptors on reproduction are compelling. Infertile couples and their health care providers must take in to account the potential impact of life style issues, dietary habits, and potential environmental exposures on reproductive performance.
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