Toxic effects of polychlorinated biphenyls on cultured rat Sertoli cells.

Polychlorinated biphenyls (PCBs) are ubiquitous and persistent environmental contaminants. In mammals, PCBs affect spermatogenesis and may be associated with Sertoli cell changes. Therefore, our aim was to evaluate in vitro toxic effects of hydroxylated PCB (PCB-22; 2',3',4',5'-tetrachloro-4-biphenylol) and PCB congener (PCB-77; 3,3',4,4'-tetrachlorobiphenyl) on Sertoli cells isolated from 19- to 21-day-old male rats. Sertoli cells incubated for 24 hours in 10(-7) M PCB-22 and 10(-8) M PCB-77, but not in 0.05% ETOH or 10(-7) M 17beta-estradiol (E2) showed morphological changes. Sertoli cells demonstrated progressive damage with higher concentrations of PCB-77 (10(-7) M). After 24 hours, 10(-7) M PCB-22 killed 20% of the Sertoli cells and equimolar PCB-77 killed 45% of the Sertoli cells in culture. At 10(-8) M, PCB-22 did not kill any significant number of Sertoli cells, whereas PCB-77 killed 40% of cells in culture. This result showed differential effects of PCB compounds, with PCB-77 being more cytotoxic than PCB-22 as tested on Sertoli cells. Because PCB-77 produced greater toxic effects, we further tested this congener on Sertoli cell lactate production. After 24 hours, lactate production by Sertoli cells treated with 10(-7) or 10(-8) M PCB-77 was significantly increased. Finally, Sertoli cells exposed to 10(-7) M PCB-77 showed disorganized and less intense F-actin staining. The results demonstrate that PCBs, but not E2, is directly toxic to Sertoli cells in vitro, and suggest this toxic effect is independent of estrogenic action.

Chronic polychlorinated biphenyls exposure on three generations of oldfield mice (Peromyscus polionotus): effects on reproduction, growth, and body residues.

Effects of chronic dietary exposure to low levels of PCBs (polychlorinated biphenyls) on reproduction, growth and whole body burdens were investigated in three generations of Peromyscus polionotus. Mated pairs were maintained on a diet containing 5 mg/kg PCBs (Aroclor 1254) for 12 months, beginning exposure as young adults; matched controls received a similar diet without PCBs. Offspring were maintained on the parental regime and paired at maturity with non-siblings in the same group. In first and second generation offspring, birth and weaning weights were significantly lower in PCB-exposed animals; in the second generation, there were also significantly fewer mice born/month, longer intervals prior to birth of the first litter, and decreased survival to weaning (25 days) among exposed mice. Whole body residue of PCBs increased significantly with each generation of exposure. This study clearly shows that chronic exposure to PCBs at a dosage of 5 mg/kg depressed fertility, growth and survival in Peromyscus, and that these effects were amplified through multigenerational exposure.

Intestinal leucine aminopeptidase and alkaline phosphatase: genetic regulation and development in mice.

Intestinal and serum leucine aminopeptidase (LAP) and alkaline phosphatase (AKP) were characterized by electrophoresis for eight inbred strains of laboratory mice. Intestinal LAP and AKP of adult mice were expressed concordantly within strains, as banded or diffuse, and concordantly for rate of migration within strains that had diffuse isozymes. All strains, except DD/S, had a single band of serum LAP and a single, diffuse zone of serum AKP. DD/S had a double band of serum LAP as well as isozymes of intestinal LAP and AKP unlike those of other strains. All strains displayed similar, neuraminidase-sensitive isozymes of intestinal LAP and of AKP prior to weaning, but after weaning there was marked sensitivity to neuraminidase only in DD/S. In interstrain crosses, banded/diffuse, migration rate, and neuraminidase sensitivity were inherited as independent autosomal traits, with indications of variable penetrance and genetic interaction.

Immunological factors in Peromyscus speciation.

Reciprocal interspecific F1 hybrids of deermice (Peromyscus maniculatus) and oldfield mice (P. polionotus) differ significantly and substantially in fetal and placental, as well as adult, size and weight. Hybrid fetal mortality is associated with large conceptus size. Skin grafts were exchanged between and within the two species to ascertain whether any relationship exists between mean graft retention time and body size of fetuses and adults. P. maniculatus skin grafted to P. polionotus rejected significantly earlier than the reciprocal xenograft. All interspecific graft combinations rejected significantly earlier than intraspecific grafts. Pre-immunization of female P. maniculatus with con- and trans-specific paternal spleen cell antigens reduced fetal, placental, neonatal, and ten-day size compared with controls. Size, weight, fertility, and graft rejection data were compared with several theoretical models. The data were consistent with the hypothesis that immunological disparity between the species could produce marked size variations in reciprocal hybrids. Multiple minor histocompatibility factors can account for large placental size and fetal mortality in Peromyscus hybrids. Physiological reproductive isolation may result from immunological differences between closely allied species.