title: Effects of polychlorinated biphenyls in CD-1 mice: reproductive toxicity and intergenerational transmission.
abstract: Several studies indicate that in utero and perinatal exposure to polychlorinated biphenyls (PCBs) induces adverse reproductive effects, but it remains unclear whether such effects may be transmitted to subsequent generations. We therefore investigated the association between maternal exposure to PCBs and reproductive health in male and female offspring over three generations. Mouse dams were fed 0, 1, 10, and 100 μg/kg/day of a PCB mixture (101 + 118) during pregnancy and lactation. PCB levels were measured in the tissues of both dams and offspring. PCB concentrations at all doses investigated were greater in the offspring than in the dams (p ≤ 0.0001) confirming that the progeny were exposed as a result of maternal exposure. In F1 offspring, exposure to PCBs resulted in reductions in (1) testis weight (p ≤ 0.05) and seminiferous tubule diameter (p ≤ 0.05), (2) sperm viability (p ≤ 0.0001) and developmental capacity (p ≤ 0.05), (3) ovary weight (p ≤ 0.05), (4) oocyte developmental capacity (p ≤ 0.05), and (5) increased follicular atresia (p ≤ 0.0001). In females, adverse effects were observed only in the F1 animals. In contrast, male offspring exhibited reduced sperm viability and altered seminiferous tubule distribution up to the third generation, showing intergenerational transmission. In summary, our data indicate that exposure to PCBs at the time of gonadal sex determination perturbed, significantly, the reproductive physiology of male and female offspring in adulthood. Furthermore, male reproductive deficiencies may be observed in at least two further generations. These findings have significant implications for reproductive health and fertility of animals and humans.
authors.affiliation: Dipartimento di Patologia Animale, Igiene e Sanità Pubblica Veterinaria, Facoltà di Medicina Veterinaria, Università degli Studi di Milano, 20133 Milano, Italy. paola.pocar@unimi.it
authors.forename: Paola
authors.initials: P
authors.lastname: Pocar
authors.forename: Nadia
authors.initials: N
authors.lastname: Fiandanese
authors.forename: Camillo
authors.initials: C
authors.lastname: Secchi
authors.forename: Anna
authors.initials: A
authors.lastname: Berrini
authors.forename: Bernd
authors.initials: B
authors.lastname: Fischer
authors.forename: Juliane-Susanne
authors.initials: JS
authors.lastname: Schmidt
authors.forename: Kristina
authors.initials: K
authors.lastname: Schaedlich
authors.forename: Stewart M
authors.initials: SM
authors.lastname: Rhind
authors.forename: Zulin
authors.initials: Z
authors.lastname: Zhang
authors.forename: Vitaliano
authors.initials: V
authors.lastname: Borromeo
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D007774:Lactation; D008297:Male; D018811:Maternal Exposure; D051379:Mice; D008815:Mice, Inbred Strains; D009866:Oogenesis / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D018812:Paternal Exposure; D011078:Polychlorinated Biphenyls / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D012727:Sex Characteristics; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology
chemical_list: D004785:Environmental Pollutants; C070055:2,3',4,4',5-pentachlorobiphenyl; C009828:2,4,5,2',5'-pentachlorobiphenyl; D011078:Polychlorinated Biphenyls