Developmental Exposure of Mice to Dioxin Promotes Transgenerational Testicular Inflammation and an Increased Risk of Preterm Birth in Unexposed Mating Partners
Developmental Exposure of Mice to Dioxin Promotes Transgenerational Testicular Inflammation and an Increased Risk of Preterm Birth in Unexposed Mating Partners
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DOI：
10.1371/journal.pone.0105084
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发表时间：
2014-08-15
期刊：
影响因子：
3.7
通讯作者：
Osteen, Kevin G.
中科院分区：
文献类型：
--
作者：
Bruner-Tran, Kaylon L.;Ding, Tianbing;Osteen, Kevin G.
TCDD（2,3,7,8-四氯二苯并-对二恶英，俗称二恶英）是一种普遍存在的环境污染物和已知的内分泌干扰物。通过小鼠模型，我们之前发现在子宫内暴露于TCDD的成年雌性小鼠（F1代）以及随后的多代（F2-F4）表现出生育能力下降和自发性早产发生率增加。进一步的研究表明，在子宫内/发育中暴露于类似TCDD的雄性F1小鼠也表现出生育能力下降，并使其未暴露的交配伴侣早产的风险增加。在此，我们扩展了这些先前的观察结果，报道雄性F1小鼠的生育能力降低与睾丸炎症有关，睾丸炎症与发育中的精子细胞凋亡、生育能力低下和未暴露的交配伴侣早产风险增加有关。值得注意的是，在没有额外毒物暴露的情况下，F2和F3雄性的睾丸炎症和生育能力下降持续存在，它们的对照交配伴侣也经常表现出自发性早产。虽然在过去的几十年里，全球男性生育能力稳步下降，但这些变化的原因还没有得到明确的确定。同样，在美国和其他国家，肺结核发病率与工业发展是同步的，这表明接触环境有毒物质和不良妊娠结局之间可能存在联系。目前大多数预防早产的临床策略都只关注母亲，而且收效有限。相反，我们的研究强烈表明，父亲的孕前睾丸健康是小鼠妊娠结局的关键决定因素。未来的临床研究应该检查男性对女性妊娠期长短的潜在影响，以及是否应该在怀孕前父母双方开始努力减少早产的发生率。
TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin, commonly known as dioxin) is a ubiquitous environmental contaminant and known endocrine disruptor. Using a mouse model, we previously found that adult female mice exposed in utero to TCDD (F1 generation) as well as multiple subsequent generations (F2-F4) exhibited reduced fertility and an increased incidence of spontaneous preterm birth. Additional studies revealed that male F1 mice with a similar in utero/developmental TCDD exposure also exhibited diminished fertility and conferred an increased risk of preterm birth to their unexposed mating partners. Herein, we extend these previous observations, reporting that reduced fertility in male F1 mice is linked to testicular inflammation which coincides with apoptosis of developing spermatocytes, sub-fertility and an increased risk of preterm birth in their unexposed mating partners. Significantly, in the absence of additional toxicant exposure, testicular inflammation and reduced fertility persisted in F2 and F3 males and their control mating partners also frequently exhibited spontaneous preterm birth. Although a steady, global decline in male fertility has been noted over the last few decades, the reasons for these changes have not been firmly established. Likewise, the PTB rate in the U. S. and other countries has paralleled industrial development, suggesting a possible relationship between environmental toxicant exposure and adverse pregnancy outcomes. Most current clinical strategies to prevent preterm birth are focused solely on the mother and have yielded limited benefits. In contrast, our studies strongly suggest that the preconception testicular health of the father is a critical determinant of pregnancy outcomes in mice. Future clinical studies should examine the potential contribution of the male to gestation length in women and whether efforts to reduce the incidence of preterm birth should be initiated in both parents prior to pregnancy.