Endocrine Compounds andReproduction

Health Effects of Endocrine Disrupting Compounds, such as Estrogen and Steroid Mimickers

The most prominent and severe health effects of EDCs are on the reproductive system, as seen with the legacy of the DES exposure and its effects on pregnancy (Bern, 1992). The increasing prevalence of abortions, reproductive tract abnormalities, and reproductive disorders, such as polycystic ovarian syndrome (PCOS) and endometriosis have impacted the ability of conception and gestation in the human population. Moreover, EDCs have decreased sperm quality and counts in males, and have altered the sex ratio of the human race. These detrimental effects, combined with females conceiving at an older age in comparison to other generations, have led to infertility rates never seen before and fertility clinics become the norm in many communities.

Endocrine Disrupting Compounds and Abortion

The association of EDCs and abortions was initially described by Savitz and his research team in 1997. The study, which involved 3,984 pregnancies in farming couples, revealed that increased abortion rates were significantly higher in couples with reported use of thicarbamates, carbaryl and other pesticides (Savitz et al, 1997). Moreover, a study by the Ontario farm family health group, revealed that spontaneous abortions of less than 12 weeks of conception, were doubled in couples exposed to phenoxy herbicides (Arbuckle et al, 1999). In addition, exposure to organochlorine pesticides have also been described in India to increase spontaneous abortions and stillbirths (Rupa et al, 1991). Significant levels of PCBs in the serum of women with missed abortions have also been recently described (Yang et al, 2006). The exact mechanisms by which EDC can cause abortions are still unknown. EDCs are believed to affect chromosome segregation at meiosis, a process still not fully accepted by the scientific community because of its serious implications. These compounds most likely effect spindle assembly and dynamics, leading to abnormal numbers of chromosomes that are not compatible with life (an aneuploidy state), as well as acting as topoisomerase inhibitors, thereby blocking the ability of this crucial enzyme to separate chromosomes as the cell divides during embryogenesis. Recent studies on bisphenol-A suggest that such chemicals could be active at low chronic exposure levels and proceed to abortive fetuses through the above mentioned processes. Experiments on cultured mouse oocytes treated with inhibitors of these biochemical reactions involved in the regulation of chromosome segregation have directed researchers to possible new mechanisms of action of environmental aneugens, of which EDCs are the primary culprits (Pacchierotti et al., 2006)

Endocrine Disrupting Compounds and Sperm Damage

Every oocyte needs a spermatocyte to fertilize it, in order to proceed through the replicative cycles to form a blastocyte, the earliest stage of an embryo. In addition to endometriosis and PCOS, there has been recent concern on the global decrease in human sperm counts. The primary culprits behind this are believed to be EDCs. To confirm this, studies were carried out by Swan et al, (2003) that revealed that sperm concentrations and motility were reduced in agricultural and semi-rural areas in comparison to their city counterparts. However, low numbers of city dwellers were also seen to have low sperm counts. A study by the Massachusetts General Hospital revealed that these city dwellers had been exposed to high levels of phthalates, as seen in their serum, that were most likely associated to be the cause of reduced sperm counts, poor sperm motility and an increase in abnormal sperm (Duty et al, 2003). The postulated mechanism of sperm damage by EDCs is not fully understood (Yang et al, 2006). A recent study by Anway et al, (2006) revealed in mice that transient exposure to EDCs at the time of male sex determination to antiandrogenic EDCs can induce reduced future spermatogenic capacity due to epigenetic alterations. Another recent study by Chang et al, (2006) further confirmed this idea. Chang’s team studied the EDC vinclozolin and its effects on families through generations, by studying human epigenetic patterns, such as methylation changes in DNA. They revealed that exposure to EDCs during embryonic gonadal sex determination was found to promote an alteration in the epigenetic (i.e. induction of imprinted-like genes/DNA sequences) programming of the male germline and that this is associated with the development of transgenerational disease states. Such changes do not only affect an individual, but the entire human race, as the changes are passed onto offspring.

Endocrine Disrupting Compounds and Male Reproduction

Previous studies have shown that the EDCs methoxychlor and vinclozolin both interfere with embryonic testis cord formation and cause increased spermatogenic cell apoptosis in the adult testis, which is a form of programmed cell death. Interestingly, studies of transient in vivo exposure to endocrine disruptors at the time of male sex determination have been described to cause a transgenerational phenotype of spermatogenic cell apoptosis and subfertility. This apparent mechanism involves altered DNA methylation and permanent re-programming of the male germ-line also (Skinner et al., 2005). Furthermore, PEs have become a major component in the typical Western fast food diet recently. Moreover, soy milk is another common source of PEs, which has been increasing in popularity recently. Soy milk has recently been used as an alternative to breast or cow's milk for infants with milk allergies. Recent concern has become evident, as the use of this particular substance is at the most vulnerable periods for estrogenic insult, which are believed to be the pre- and neonatal periods when irreversible damage can be inflicted on the developing germinal epithelium of an infant. Use of soy milk should therefore not be used in infants until more comprehensive and larger studies have been conducted on its long-term effects as an EDC (West et al., 2005).

Endocrine Disrupting Compounds and Endometriosis, Diabetes and Infertility

EDCs can cause numerous estrogen insufficient and androgen excess states. Endometriosis is a disease defined by the presence of endometrial glands and stromal tissue outside of the uterine cavity, which causes symptoms such as pain and discomfort during menses. It is though that exposure to PCBs or dioxins can provoke this disease; however, there is still debate in the medical literature concerning whether this is true (Pauwels et al, 2001). This is also true concerning polycystic ovarian syndrome (PCOS). This previously rare syndrome has reached epidemic proportions in the USA, and it is believed that EDCs are at fault. The syndrome consists of infertility, insulin resistance (diabetes) and elevated levels of androgens in females.
Apart from EDCs affecting the reproductive system of humans, they also play a role in inducing diabetes. For instance, the Seveso accident showed that exposure to dioxin induced adult-onset diabetes. Subsequently, there was an increased rate of diabetes induced mortality in high dioxin exposure zones (Baccarelli et al, 1999). Furthermore, Agent Orang,e which was a widely used defoliant in the Vietnam War, has been shown to cause an increase in the development of adult-onset diabetes in war veterans (Knopper, 2002). A 1999 NIOSH study (Calvert et al, 1999) reported that individuals having high levels of serum dioxin were prone to having an elevated incidence of Type 2 diabetes. In addition, another EDC that become implicated in Type 2 diabetes is TCDD. Numerous reports have implicated TCDD in causing diabetes (Longnecker and Michalek, 2000; Cranmer et al, 2000).

Endocrine Disrupting Compounds and Precocious Puberty

Precocious puberty is a condition where pubertal changes occur at an earlier age than what is expected. The cause of this condition is well-known to be from EDCs. Numerous reports from developing countries have shown that pubertal signs were detected much earlier than normal following an increase in xenoestrogen exposures like plastics and insecticides (Juul et al, 2002; Yang et al, 2006). In addition, studies in Belgium were conducted to further investigate EDCs impact on puberty. The study involved comparing non-native girls from developing countries with precocious puberty to Belgian-born girls. The study was performed through screening the plasma of girls for pesticides. The results showed a p,p’-DDE increase in the plasma of the non-native girls, whereas no levels of pesticides were detected in Belgian-born girls (Craen et al., 2001). Moreover, for these studies, it can be seen that EDCs are having a larger impact in developing countries. A secular trend in the male pubertal timing has also been observed. A study that was conducted that involved comparing European boys and boys from the United States (US). The results that were obtained revealed that pubertal onset in boys from the US (American and African-American) occurred at an age earlier than in European boys. For example, US boys entered puberty at a mean age of 9.5 years (Herman-Giddens et al., 2001), whereas European boys entered puberty between the ages of 11.2 and 11.8 years (Largo and Prader, 1983; Lindgren, 1996; Fredriks et al., 2001; Danubio et al., 2004; Hertel et al., 2006).

Endocrine Disrupting Compounds and the Immune System

In addition to disrupting our endocrine systems, immune alterations are also affected by EDCs. EDCs have been shown to be toxic to the organ that matures our T cells, the thymus. Toxicity from PCBs, PCDFs, and PCDDs in the thymus is due to EDCs binding androgen receptors leading to fluctuations in thymic hormones (IPCS, 2002). Moreover, not only are thymic hormones affected, but immunoglobulins, such IgA and IgM that protect us from infection from invading viruses and bacteria. PCB-contaminated edible oils (PCBo) have been shown to be the main culprits. Studies with PCBo have shown that serum levels of IgA and IgM are subsequently decreased because of their use. It was also shown that PCBo have the ability to weaken cellular immunity (CM) (Irvine et al, 2004). CM is mediated by T and Natural Killer (NK) cells, which are of prime importance in fighting not only infections, but cancers. T cells, can either be T-helpers (Th), the coordinators of an immune response, and T-suppressors (Ts), the regulators of an immune response. TCDDs and PCBs have been shown to decrease T cell levels in general (Yang et al, 2006). For example, Ello et al. (2005), investigated the impacts of TCDD and PCB exposures in CM by observing peripheral blood for concentrations of T cells, which can be related to their activities. The team showed that the overall concentrations of T cells decreased and that cell ratios of Th/Ts were also lowered as a result of TCDD and PCB exposures. Lastly, Esser et al., (1996) performed an examination on industrial workers whom had been exposed over the years to doses of TCDD, in order to observe if TCDD impacted their immunity. It was concluded that TCDD did impact their immune function, as their response to interleukin-2-boosted proliferation was reduced, a process by which T cells duplicate themselves in order to fight millions of bacteria, viruses and cancer cells.

Phytoestrogens and Health Effects

Even though phytoestrogens are naturally occurring compounds found in plants, they can have numerous profound affects to the health of individuals. For example, phytoestrogens have the ability to reduce cardiovascular disease, osteoporosis and menopausal symptoms (Gardner et al, 1998). Furthermore, one type of phytoestrogen, commonly known as soy has been shown to decrease breast cancer risk. A reduction in breast cancer risk was observed in women whom consumed foods with soy once per week. In addition, it was found that soy foods also reduce the risk of endometrial cancer (Goodman et al, 1997) and the risk of prostate cancer by 70% (Fraser et al, 1998).

Soy and Health Effects

These beneficial effects from soy products in adults, however, are met with different results in the developing infant. It is well known that feeding practices in infancy have an affect on the development of autoimmune diseases that appear later in life. This is why infants start with simple foods, like cereal and grains, and later on begin eating meats and vegetables. Soy milk ties into this development and the appearance of autoimmune diseases. In a study conducted by Fasano et al., (1990) children with autoimmune thyroid diseases were seen to have been exposed to soy-based milk formulas after the prenatal period, in contrast to infants being fed with cow-based milk formulas.

Pregnancy and Endocrine-Disrupting Compounds

In addition, pregnant mothers and their health status can greatly affect the health of their offspring. It has been hypothesized that there is an increased risk of testicular cancer in the offspring of smoking pregnant mothers. A study by Akre et al. (2003), revealed that this hypothesis was correct. Tobacco contains numerous deleterious compounds, of which mixed EDCs like pesticides, PAHs and cadmium are part of. Furthermore, smokers have been shown to be at increased risk of ovarian cancer in comparison to non-smokers, possible secondary to containing EDCs (Coogan et al, 2004).

 

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