ReviewImpact of endocrine-disrupting compounds (EDCs) on female reproductive health
Introduction
Environmental chemicals (ECs), including endocrine disrupting compounds (EDCs), comprise many different chemicals from a wide range of (primarily) anthropogenic, industrial, agricultural and domestic sources and in recent decades it has become increasingly clear that they have the capacity to interfere with female reproductive development and function in a wide range of species including humans (Woodruff and Walker, 2008).
Section snippets
Are EDCs implicated in Ovarian Dysgenesis Syndrome (ODS)?
The term testicular dysgenesis syndrome (TDS) is used to describe the phenotypic consequences of endocrine disruption in the human male (Skakkebaek et al., 2001). These include reduced adult sperm counts and increased incidences of hypospadias (malformation of the urogenital tract), cryptorchidism (testis maldescent) and testicular cancer. TDS has a developmental origin and the processes involved are being elucidated (Sharpe and Skakkebaek, 2008). There is, no evidence for such a tight set of
EDC effects on trophoblast and placental function
During early embryonic development, potential targets of EDCs include cell cleavage and differentiation, cell lineage determination, methylation, implantation, maintenance of pregnancy and organogenesis (Table 1). Polychlorinated biphenyls (PCBs), dioxins (such as TCDD) and phthalates (such as DEHP) can affect cell lineage formation and trophoblast function in blastocysts and these chemicals are known to cross the placental barrier and to disturb embryonic development in humans (Myatt, 2006).
EDCs can disrupt the hypothalamo-pituitary–gonad (HPG) axis
While reproduction is dependent on gonadal activity, primary control is exerted via regulation of GnRH secretion from the hypothalamus and subsequent gonadotrophin release from the pituitary gland. Exposure to some ECs can have adverse effects on the hypothalamo-pituitary gland complex in a range of different adult, prepubertal (Adewale et al., 2009) and foetal animals. The activity of the GnRH neurosecretory system is sexually differentiated as the result of steroid exposure during foetal
EDCs and the timing of puberty
Puberty is a multifaceted developmental process that is under the control of different hormonal regulatory mechanisms and, because there can be significant social consequences of premature puberty, this section will focus on the human. Puberty is characterised by activation of the hypothalamic-pituitary–gonadal axis, the appearance of secondary sexual characteristics and a growth spurt (Kakarla and Bradshaw, 2003). The onset of puberty begins late in childhood and results in the individual’s
Factors leading to gender differences in EDC exposure
The processes that determine tissue exposure to EDCs appear, at first sight, to be both simple and independent of gender. However, gender-related factors can affect exposure to EDCs, indirectly, through differences in the ecology of the two sexes. e.g. in many deer species, males and females inhabit different geographic areas and/or exploit different feed resources and may therefore be exposed to subtly different EDC burdens. In mammals, gender differences in physiology, especially those
Evidence for epigenetic effects of EDCs
Given the level of interest in epigenetic programming of early development over the past decade, the paucity of primary data on the effects of EDCs on epigenetic programming through the germline, particularly the female germline, is perhaps surprising (Zama and Uzumcu, 2009, Zama and Uzumcu, 2010, Bernal and Jirtle, 2010). This is a critical deficiency since such epigenetic changes may induce deficits or alterations in the developmental trajectory of unexposed generations, i.e. true
Conclusions and perspective
The issue of the nature and extent of disturbance of female reproductive development and subsequent adult reproductive health remains complex and, in some cases, confused. There is a considerable need for additional research, especially into the effects of low-dose exposures, pre- and post-natally, to complex chemical cocktails which include EDCs, in other words, “real-life” exposures. We propose a series of take-home messages from recent findings in the field:
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The effects of chemicals on female
Acknowledgements
The study was partly supported by Grants from the Wellcome Trust (080388) to P.A.F., N.P.E and S.M.R. and the European Community’s Seventh Framework Programme (FP7/2007-2013) under Grant Agreement No. 212885, to P.A.F., S.M.R., B.F., P.P., R.G.L., K.D.S. and Grampian NHS Endowments (08/02) to P.A.F., P.J.O.S., S.B.
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