In Utero and Lactational Exposure to an Environmentally Relevant Organochlorine Mixture Disrupts Reproductive Development and Function in Male Rats1

Abstract

We hypothesized that in utero and lactational exposure of male rats to a mixture of more than 15 organochlorines, resembling that found in blubber from northern Quebec seals, alters reproductive development and function. Female rats were gavaged with either corn oil (controls) or the organochlorine mixture in increasing doses (low, medium, and high) for 5 wk before mating and through gestation. Developmental effects were monitored in the male offspring from Postnatal Day (PND) 2 until PND 90. The high-dose mixture reduced the number of pups per litter, percentage of live offspring, and pup weights (P < 0.05). Because only three rats from the high-dose treatment survived, data from this group beyond PND 2 were not included in the statistical analyses. As assessed by the time of preputial separation, puberty was delayed in the pups from treated dams (P < 0.05). Testes weights in the medium-dose group were greater than those in controls on PND 21 (P < 0.05). Ventral prostate weights were lower for the medium-dose group on PND 60 (P < 0.05). On PND 90, weights of the epididymis, ventral prostate, and seminal vesicle of the medium-dose rats were reduced compared to those of controls (P < 0.05). On PND 90, sperm motility parameters assessed by computer-assisted sperm analysis were altered in the low- and medium-dose groups (P < 0.05). Testicular and epididymal morphology was severely affected in rats exposed to the high dose of the mixture. Serum testosterone, LH, FSH, prolactin, and total thyroxine levels did not differ because of organochlorine treatment. Therefore, in utero and lactational exposure to an environmentally relevant organochlorine mixture adversely affects the reproductive system of male rats, perhaps via antiandrogenic effects during testis development, suggesting a possible reproductive health hazard for humans and other species.

Fertility and Markers of Male Reproductive Function in Inuit and European Populations Spanning Large Contrasts in Blood Levels of Persistent Organochlorines

“…In addition, it can be argued that the estrogenic and androgenic equivalents contributed by xenobiotics in these highly exposed populations only are a few percent of the endogenous hormone activity, even when possible higher bioavailability of the xenobiotics is taken into consideration (Toft et al 2007). However, in controlled rodent experiments, effects on reproductive function have been observed at very low exposure levels, particularly after exposure during the fetal and postnatal development periods (Anas et al 2005; Mably et al 1992)—an issue not explicitly addressed by this project. Thus, the picture with respect to mechanisms at the cellular level is far from clear, and the possibility cannot be excluded that POPs also exert toxic effects independent of hormonal actions.…”

“…There are several pieces of evidence that indicate reproductive organs are more sensitive to detrimental effects of chemicals during critical periods of fetal and postnatal development than during adult life (e.g,, Anas et al 2005). It is therefore important to acknowledge that the research reviewed in this article does not explicitly address fetal exposures.…”

Endocrine distrupting chemicals and human health: The plausibility of research results on DDT and reproductive health

“…The physiologicallyrelevant metabolized extracts used by Campagna et al in 2009 27 contained organochlorines concentrations 5,000 to 10,000-fold lower than the environmentally relevant mixture that induced marked effects on male reproductive function in vivo in studies published by Bailey in 2002 28 and Anas et al in 2005. 29 However though the study concluded that exposure to the environmentally-relevant organochlorine mixture altered normal sperm fertility parameters in vitro the concentrations used were far higher than those found in human body fluids. Furthermore a dose response variation that is crucial in determining effects of substances was found to have no significant variation in the results when the dose is varied amongst the study participants in some studies.…”

Effects of an Environmentally Relevant Organochlorine Mixture and a Metabolized Extract of This Mixture on Porcine Sperm Parameters In Vitro

“…Although most studies have tested the effects of only 1 or 2 chemicals (Pflieger‐Bruss and Schill, 2000; Kuriyama and Chahoud, 2004), populations are simultaneously exposed to a variety of contaminants. In earlier studies, we demonstrated that in utero and lactational exposure to an environmentally relevant organochlorine mixture adversely affected male reproduction, including decreased sperm motility, in the rat and pig models even at low, environmentally pertinent concentrations (Bailey, 2002; Anas et al, 2005). We also showed that in vitro exposure of frozen‐thawed boar sperm to the original organochlorine mixture decreased sperm motility and viability in a dose‐dependent manner (Campagna et al, 2002).…”