ESSM Newsletter # 40

7 ESSM Today Endocrine disruption and sexual dysfunction noted that up to 20% of animals suffered from multiple gonads (up to 6 in a single animal) or were hermaphrodites [19]. This study was featured in a legal action against Syngernta (manufacture of Atrozene) and was a seminal case in public outcry at the role of potential environmental EDCs. However, Goodman et al performed a systematic review of the human studies linking Atrozene with pregnancy out- comes and noted the quality of data was poor on the basis that most studies used aggregate rather than individual-level information [20]. Topperia and Skelteberg postulated the tes- ticular dysgenesis syndrome theory to unify increasing rates of testicular cancer, infertility and reproductive abnormalities as a results of endocrine “disruption of embryonal program- ming and gonadal development during foetal life”[21]. They noted that animal studies inves- tigating the impact of exposure to vinclozolin demonstrated an association with reproductive abnormalities. Vinclozolin is a fungicide that has been shown at low levels to produce sub- tle alterations in sexual differentiation of the external genitalia, ventral prostate, and nipple tissue in male rat offspring [22]. Uzumcu et al demonstrated that vinclozolin exposure may have different effects depending on the time exposure. Transient exposure of vinclozolin to pregnant rats between embryonic days 8 – 14 (a period of sex determination and testis mor- phogenesis) resulted in germ cell apoptosis and reduction in sperm motility later in life. However, this did not impact fertility compared to control animals [23]. Interestingly, research by Anway et al high- lighted that the impact of vinclozolin on human health may be transgenerational. In his study they demonstrated that vinclozolin exposure to a pregnant rat resulted in the adult sons having a decreased sperm number and in- creased incidence of male infertility. These effects were transmitted via the male germ line to the majority of all subsequent male generations [24]. This highlights another facet to the complexity of EDCs assessment in that the effect can present years or generations following the initial exposure. Unfortunately, there are limited studies on the impact of intrauterine vinclozolin exposure in humans. There is growing research exploring the re- lationship of cryptorchidism with exposure to EDCs. Studies have linked rates of cryptor- chidism to areas with higher levels of pesticide use. However, these studies were limited by methodical issues namely selection bias and also the classification of the municipalities based on pesticide use [25] [26]. . Other stud- ies evaluating biochemical and histological levels of pesticides (Heptachloroepoxide and Hexachlorobenzene) in mothers of and chil- dren with cryptorchidism have had conflicting results [27] [28]. The Endocrine society noted that the research evaluating EDCs and hypospadias is incon- sistent and fraught with methodical issues [3]. Rocheleau et al’s meta analysis demon- strated an association between hypospadias and exposure to pesticides. However, there was potential pesticide exposure misclassi- fication and it is not clear which chemical caused hypospadias [29]. Plastics and plasticisers BPA Bisphenol A (BPA) is one of the highest volume chemicals produced worldwide and present in many plastics used for food and drink storage [30]. The effects of BPA vary with the dose and time of exposure. The prenatal and neonatal period represent the most vulnerable window of exposure and may affect time of puberty [31] but also development of abnormal prostatic [32] and mammary tissues [33] which may predispose to neoplasia. However, Melnick et al noted that several large studies in animals replicated no abnormalities with low dose BPA. The authors attribute these discrepancies be- tween various studies to different diets, strains of animals and dosing of BPA [34]. Li et al demonstrated an association between urinary levels of BPA and sexual function in 427 male workers. They found that increasing urine BPA level was associated with decreased sexual desire, more difficulty having an erec- tion, lower ejaculation strength (P < 0.001), and lower level of overall satisfaction with sex life (P < 0.01) [35]. There are limited human studies evaluating the impact of BPA on ovarian development but animal studies suggest that it induces follicle atresia and inhibits growth [36]. Phthalate Phthalate is predominantly used as a plasti- ciser (a substance added to plastics to modify its properties i.e. increase flexibility). It is in many items including household products (shampoos, soaps), children toys, packaging and medical devices. Such is its widespread use it is not surprising researchers found measurable levels of many phthalate me- tabolites in the general population and noted that phthalate exposure is widespread in the U.S. population [37]. Several studies have implicated phthalate as a trigger for male reproductive abnormalities in rats [38]. Research in animal studies have connected phthalate exposure with genital tract abnormalities including hypospadias, cryptorchidism and formation of areolae in men [39]. However, human studies evaluating the impact of in utero phthalate exposure to the aforementioned reproductive abnormalities are limited and conflicting. There have been several human studies linking high urinary phthalate metabolite concentra- tion and abnormal semen quality [40] [41]. However, the majority of these studies use phthalate metabolites as a proxy for phtha- lates exposure and the cohorts are based on populations of infertile men rather than the general population. Nassan et al performed a crossover-crossback prospective design utilising mesalamine medications coated