Dipartimento di Patologia Animale, Igiene e Sanità Pubblica Veterinaria, Facoltà di Medicina Veterinaria, Università degli Studi di Milano, 20133 Milano, Italy.
Toxicol Sci. 2012 Mar;126(1):213-26. doi: 10.1093/toxsci/kfr327. Epub 2011 Dec 7.
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.
几项研究表明，多氯联苯（PCBs）在子宫内和围产期的暴露会导致不良的生殖影响，但目前尚不清楚这些影响是否可能传递给后代。因此，我们研究了母体暴露于多氯联苯与雄性和雌性后代三代生殖健康之间的关系。妊娠和哺乳期的鼠母鼠分别以 0、1、10 和 100μg/kg/天的剂量喂食多氯联苯混合物（101+118）。测量了母鼠和后代组织中的多氯联苯水平。在所研究的所有剂量下，后代组织中的多氯联苯浓度均高于母鼠（p≤0.0001），证实后代因母体暴露而受到暴露。在 F1 后代中，多氯联苯暴露导致（1）睾丸重量（p≤0.05）和生精小管直径（p≤0.05）降低，（2）精子活力（p≤0.0001）和发育能力（p≤0.05）降低，（3）卵巢重量（p≤0.05）降低，（4）卵母细胞发育能力（p≤0.05）降低，（5）卵泡闭锁增加（p≤0.0001）。在雌性中，仅在 F1 动物中观察到不良影响。相比之下，雄性后代在第三代之前表现出生精小管分布减少和精子活力降低，显示出跨代传递。总之，我们的数据表明，在性腺性别决定时暴露于多氯联苯会显著扰乱雄性和雌性后代成年后的生殖生理。此外，至少在两代中可能观察到雄性生殖缺陷。这些发现对动物和人类的生殖健康和生育能力具有重要意义。
