Effects of Perinatal Polychlorinated Biphenyls on Adult Female Rat Reproduction: Development, Reproductive Physiology, and Second Generational Effects1

Abstract

Perinatal exposures to endocrine-disrupting chemicals, such as polychlorinated biphenyls (PCBs), can cause latent effects on reproductive function. Here, we tested whether PCBs administered during late pregnancy would compromise reproductive physiology in both the fetally exposed female offspring (F1 generation), as well as in their female offspring (F2 generation). Pregnant Sprague-Dawley rats were treated with the PCB mixture, Aroclor 1221 (A1221; 0, 0.1, 1, or 10 mg/kg), on Embryonic Days 16 and 18. Somatic and reproductive development of F1 and their F2 female offspring were monitored, including ages of eye opening, pubertal landmarks, and serum reproductive hormones. The results showed that low doses of A1221 given during this critical period of neuroendocrine development caused differential effects of A1221 on F1 and F2 female rats. In both generations, litter sex ratio was skewed toward females. In the F1 generation, additional effects were found, including a significant alteration of serum LH in the 1 mg/kg A1221 group. The F2 generation showed more profound alterations, particularly with respect to fluctuations in hormones and reproductive tract tissues across the estrous cycle. On proestrus, the day of the preovulatory GnRH/gonadotropin surge, F2 females whose mothers had been exposed perinatally to A1221 exhibited substantially suppressed LH and progesterone concentrations, and correspondingly smaller uterine and ovarian weights on estrus, compared with F2 descendants of control rats. These latter changes suggest a dysregulation of reproductive physiology. Thus, low levels of exposure to PCBs during late fetal development cause significant effects on the maturation and physiology of two generations of female offspring. These findings have implications for reproductive health and fertility of wildlife and humans.

Environmental Endocrine Disruption of Brain and Behavior

“…Laboratory rodent models of DES are quite consistent with the human data, as fetal DES is associated with the latent development of uterine cancer (Newbold et al, 2006). This fetal basis of adult disease also applies to the context of hormones and reproductive behaviors (Gore, 2008;Gore et al, 2006;Steinberg et al, 2007Steinberg et al, , 2008.…”

“…In particular, LH and progesterone levels were significantly lower on proestrus in the F2-PCB females compared to the F2-vehicle group. These results show that exposure of the F2 rats' pregnant grandmother to PCBs had effects on the F2 descendants' reproductive physiology in adulthood (Steinberg et al, 2008). We are currently developing models to assess effects of F0 exposure to PCBs up through the F3 generation.…”

“…We also evaluated the female F2 generation of offspring in early adulthood for several reproductive physiological parameters. These F2 rats exhibited aberrant hormone profiles across the estrous cycle (Steinberg et al, 2008). In particular, LH and progesterone levels were significantly lower on proestrus in the F2-PCB females compared to the F2-vehicle group.…”

“…One of us (Andrea C. Gore) investigated effects of low-level fetal PCB (Aroclor 1221) exposure to F0 rat dams during the critical period of brain sexual differentiation (gestational days 16 and 18) on the reproductive development and behavior in the F1 generation of female offspring in adulthood (Steinberg et al, 2007(Steinberg et al, , 2008. We also evaluated the female F2 generation of offspring in early adulthood for several reproductive physiological parameters.…”

Productivity, embryo and eggshell characteristics, and contaminants in bald eagles from the Great Lakes, USA, 1986 to 2000

“…There is evidence particularly from the mammalian literature demonstrating that in utero or lactational exposure to TCDD or PCBs affects neuro-endocrine and sexual development [51,52]. Strong evidence is lacking for birds, in part due to a lack of experimental studies [50].…”