Human exposure to endocrine-disrupting chemicals and prenatal risk factors for cryptorchidism and hypospadias: a nested case-control study

摘要: Ten years ago, it was hypothesized that exposure of the developing male fetus to environmental estrogens may be responsible for anomalies sexual maturation and reproductive function in adult life (Anonymous 1995). Male differentiation functioning are critically dependent on a balanced androgen:estrogen ratio. In this regard, two common reproductive-tract malformations—cryptorchidism (failure one or both testicles descend into scrotum) hypospadias (urethral opening ventral side penis)—are birth defects prenatal origin related utero estrogens/androgens. Animal (Edwards et al. 2006) human data (Nurminen 2001) point toward causal relationship between pesticides during pregnancy development congenital malformations. fact, parental involvement agricultural work and/or has been associated with higher risk wide range malformations (Kristensen 1997). For example, Spain, maternal activity month before conception first trimester followed by 3-fold increase bearing child malformation (Garcia 1999). Moreover, an ecologic investigation variations orchidopexy rates Spanish province Granada found association cryptorchidism (Garcia-Rodriguez 1996). A later retrospective case–control study same geographic area suggested father’s employment agriculture (Rueda-Domingo 2001). Because their persistence environment, contaminants soil, water, wildlife present tissues mothers children, especially regions devoted intensive (Botella 2004; Cerrillo 2006; Olea Their ubiquity supports plausibility embryo-fetal pregnancy, although mutagenic epigenetic germ cell damage cannot ruled out. Some organochlorine endocrine disrupting chemicals (EDCs) (Soto 1995), defined as exogenous substances mixtures ability disrupt hormonal homeostasis, alter system functions, consequently cause adverse health effects intact organism its progeny sub-populations. EDC now considered include not only estrogenic androgenic properties but also those antihormonal enzymatic/metabolic (Almstrup 2002). Maternal urogenital malformations, semen quality impairment, testicular, prostate, ovarian, breast cancer (Koifman 2002). Thus, excess reported sons women working farming, horticulture (Weidner 1998), whereas occupation father had no influence either hypospa-dias. Kristensen coworkers (1997), who studied different farm purchases tractor pesticide spraying equipment, positive moderate hypospadias. However, when assessment based (farmers vs. other jobs), significant differences were observed. Occupational nested conducted Pierik (2004), Irgens (2000). contrast above studies, authors (Restrepo 1990), occupational EDCs mother (Aho 2000; Vrijheid 2003), serum levels dichlorodiphenyl-dichloroethene (DDE) third (Longnecker These inconsistent results led conclusion epidemio-logic studies do provide sufficient grounds support role more focused methodology is required, specific markers (Dolk 2003; Silva 2002; Vidaeff Sever 2005). The need disruptor hypothesis prompted European Community prospective multi-center cohort five countries (Denmark, England, Finland, France, Spain) explore possible disruptors sex disorders. mother–child established (southern Spain), which main factors study, we examined cryp-torchidism factors, special emphasis xenoestrogens, estimated combined extracted from placentas.