Dioxin-induced changes in epididymal sperm count and spermatogenesis

Abstract

A single in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gestation day 15 decreased epididymal sperm count in adult rats and thus was used to establish a tolerable daily intake for TCDD. However, several laboratories have been unable to replicate these findings. Moreover, conflicting reports of TCDD effects on daily sperm production suggest that spermatogenesis may not be as sensitive to the adverse effects of TCDD as previously thought. We performed a PubMed search using relevant search terms linking dioxin exposure with adverse effects on reproduction and spermatogenesis. Developmental exposure to TCDD is consistently linked with decreased cauda epididymal sperm counts in animal studies, although at higher dose levels than those used in some earlier studies. However, the evidence linking in utero TCDD exposure and spermatogenesis is not convincing. Animal studies provide clear evidence of an adverse effect of in utero TCDD exposure on epididymal sperm count but do not support the conclusion that spermatogenesis is adversely affected. The mechanisms underlying decreased epididymal sperm count are unknown; however, we contest [corrected] that epididymal function is the key target for the adverse effects of TCDD.

Spermatogenesis disruption by dioxins: Epigenetic reprograming and windows of susceptibility

“…In the most recent review of existing bodies of literature on the effect of dioxins on male reproductive health, Foster and others [56] found no convincing evidence of treatment-related effect of environmentally-relevant doses of dioxins on weight and/or morphology of testis, changes in Sertoli cell structure and count, and functioning of hypothalamic-pituitary-testicular axis. Thus, the authors concluded that effects of dioxins on sperm count can be due to induced changes in epididymal structure and function rather than changes in spermatogenesis or the testis itself.…”

Polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans

“…A single exposure of rats to 0.064 μg 2,3,7,8-TCDD/kg body weight on GD 15 resulted in a significant decrease (36%) in epididymal sperm counts (Mably et al, 1992). Foster et al (2010) propose that the primary effect of 2,3,7,8-TCDD in relation to reduced sperm counts are due to developmental abnormalities of the male reproductive tract and epididymal structure and/or function. However, results of recent studies generally have not indicated an effect of in utero exposure to 2,3,7,8-TCDD on epididymal sperm counts.…”

“…Fetal and early developmental exposures to these chemicals are particularly devastating, and can have different outcomes from adult exposure (Crews et al, 2000). As stated by Steinberg et al (2008), latent effects of early exposures include, but are not limited to, depressed circulating thyroid hormone and abnormal thyroid cytology (Porterfield, 1994;Goldey et al, 1995;Morse et al, 1996a;Chauhan et al, 2000;Bansal et al, 2005), developmental effects of the heart, palate and kidney (Foster et al, 2010), delayed cognitive development (Chen et al, 1992;Jacobson and Jacobson, 1997), altered sensory and motor abilities (Bowman et al, 1981;Laskey et al, 2002;Roegge et al, 2004), reproductive impairment (Sager and Girard, 1994;Arnold et al, 1995;Meerts et al, 2004;Yang et al, 2005) and compromised neural function (Morse et al, 1996b;Provost et al, 1999;Donahue et al, 2004;Seegal et al, 2005).…”

“…Mocarelli et al (2008) reported that men exposed to 2,3,7,8-TCDD during the 1976 Seveso incident prior to puberty had reduced sperm count and motility as adults, while males exposed during adolescence exhibited increased sperm counts and motility. Foster et al (2010) state that of the reproductive/developmental effects of 2,3,7,8-TCDD, decreased sperm counts are considered to be the most sensitive outcome. Foster et al (2010) state that of the reproductive/developmental effects of 2,3,7,8-TCDD, decreased sperm counts are considered to be the most sensitive outcome.…”

“…Foster et al (2010) state that of the reproductive/developmental effects of 2,3,7,8-TCDD, decreased sperm counts are considered to be the most sensitive outcome. The World Health Organization (WHO) used this endpoint in establishing a tolerable daily intake for 2,3,7,8-TCDD of approximately 2 pg/kg body weight/day (Foster et al, 2010). The World Health Organization (WHO) used this endpoint in establishing a tolerable daily intake for 2,3,7,8-TCDD of approximately 2 pg/kg body weight/day (Foster et al, 2010).…”