PCBs, Thyroid Hormones, and Ototoxicity in Rats: Cross-Fostering Experiments Demonstrate the Impact of Postnatal Lactation Exposure

Abstract

Previous research has demonstrated the sensitivity of the developing rat to the hypothyroxinemic and ototoxic effects of perinatal exposure to Aroclor 1254 (A1254). We tested the hypothesis that postnatal exposure via lactation is the major cause of the ototoxicity by cross fostering animals at birth. Primiparous rats (22-24/dose) received 0 or 6 mg/kg A1254 (po in corn oil) from gestation day (GD) 6 to postnatal day (PND) 21. On the day of birth, half of the treated litters and half of the control litters were cross-fostered, resulting in the following groups: Ctrl/Ctrl (controls); A1254/A1254 (perinatal exposure); A1254/Ctrl (prenatal exposure only); and Ctrl/A1254 (postnatal exposure only). We assessed offspring at a number of ages for: serum thyroid hormone concentrations, liver and brain concentrations of PCBs, body weight, mortality, age of eye opening, auditory startle amplitudes, and auditory thresholds for 1 kHz and 40 kHz tones. Circulating thyroxine (T(4)) concentrations were sharply reduced at GD 21 in the A1254-exposed group, and on PND 3, 7, 14, and 21 in the A1254/A1254 and the Ctrl/A1254 groups. Smaller decreases in T(4) were observed in the A1254/Ctrl group on PND 3, 7, and 14. PCB concentrations in the liver on PND 21 were sharply elevated in the A1254/A1254 and Ctrl/A1254 groups. Much smaller increases were seen in the A1254/Ctrl group. Age of eye-opening and startle amplitudes were unaffected by treatment. A1254 exposure caused permanent hearing deficits (20 dB increase) at the low frequency (1 kHz) in the A1254/A1254 and Ctrl/A1254 groups. The present findings demonstrated that the critical period for the ototoxicity of developmental A1254 exposure is within the first few postnatal weeks in the rat. This effect is consistent with the greater degree of postnatal hypothyroxinemia resulting from the greater magnitude of exposure that occurs postnatally via lactation.

The effects of prenatal PCBs on adult female paced mating reproductive behaviors in rats

“…Our results suggest that A1221 may alter the amount of time that females choose to spend with males after a mating event. Consistent with this, other reports on PCBs have shown effects on other sensory and motor parameters in many systems, including audition (Crofton et al, 2000), sensory and motor nerve conduction velocities (Chen et al, 1985) and vision (Kremer et al, 1999).…”

“…Our results suggest that A1221 may alter the amount of time that females choose to spend with males after a mating event. Consistent with this, other reports on PCBs have shown effects on other sensory and motor parameters in many systems, including audition (Crofton et al, 2000), sensory and motor nerve conduction velocities (Chen et al, 1985) and vision (Kremer et al, 1999).Not all aspects of the suite of mating behaviors were significantly affected by early PCB treatment. We did not detect significant differences in lordosis quotient (LQ) among treatment groups, although there was a non-significant trend for the highest LQ in the 1 mg/kg group.…”

Developmental Exposure to 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107): Long-Term Effects on Brain Development, Behavior, and Brain Stem Auditory Evoked Potentials in Rats

“…However, the slight prolongation of latencies in metaboliteexposed groups may indicate effects on the neural part of the auditory system. Alternatively, this may be explained by the observations of Crofton et al (2000b), who showed in crossfostering studies that lactational exposure to Aroclor (postnatally) is the major cause of ototoxicity.…”

Permanently compromised NADPH-diaphorase activity within the osmotically activated supraoptic nucleus after in utero but not adult exposure to Aroclor 1254

“…Indeed, experimental animals appear to be especially sensitive to PCB exposure during the postnatal period as manifested by levels of thyroxine, which are similarly reduced after in utero followed by postnatal dosing (perinatal; Crofton et al, 2000;Goldey et al, 1995;Shah et al, 2011). In support of this, others have shown that perinatal dosing can alter levels of male reproductive steroids in adulthood (Hany et al, 1999).…”

“…levels (Bowers et al, 2004;Crofton et al, 2000;Hany et al, 1999) and postnatal or adult exposure reduces reproductive function in male and female rats (Jonsson et al, 1975;Sager, 1983). In human studies developmental exposure to Aroclor 1254 has been associated with attention and learning deficits in children (Jacobson and Jacobson, 2003) and with abnormal reproductive function and reduced testosterone (Bell, 2014).…”