Three-generation Human Study of Reproductive Effects of Marine Food Contaminants

描述（由申请人提供）：近几十年来，男性生殖障碍已成为一个重要的公共卫生问题：睾丸癌的发病率增加，精液质量下降，某些地区隐睾症和尿道下裂的发病率似乎有所增加。这些情况被认为反映了一种被称为睾丸发育不良综合征（TDS）的潜在实体，在胎儿生命中有一个共同的起源。TDS似乎还与其他不利影响有关，例如出生性别比下降。虽然病因不明，但怀疑内分泌紊乱，可能是由于持久性有机氯污染物。这一领域的研究受到阻碍，因为某些疾病相对罕见，而且对男性生殖功能的评估只有在成年后才可行，即在初次接触有毒物质多年之后。我们选择在苏格兰北部的法罗群岛进行一项研究，那里的居民越来越多地接触到传统海洋食物中可疑的内分泌干扰物，其中可能包括引航鲸的肉和鲸脂。在这个相当同质的群体中，已知存在较宽的暴露间隔，并且与混杂因素无关。在法罗群岛成年人中，可从母亲的饮食习惯和目前的血清持久性有机氯物质浓度中估计出产前暴露水平。因此，这项研究将检查被认为与内分泌紊乱和TDS有关的生殖结果。这些指标包括精液质量、携带X/Y染色体的精子比例、精子的染色质稳定性、新生儿的性别比例和等待怀孕的时间。这项研究将包括400对怀孕夫妇，他们的母亲也被邀请参加。由于怀孕夫妇中的男性构成了一个选定的人群（预计约250人将提供精液样本），我们还将检查来自普通人群（20-24岁）的250名年轻男性的精液质量参数以及他们的暴露情况。因此，这项研究的目的是提供证据，证明无论是从产后来源还是从母亲食用海鲜引起的产前暴露中，内分泌干扰物的增加是否与男性和女性的生殖异常有关。精子质量下降、生育能力下降和性别比下降是具有重大公共卫生利益的生殖结果。目前的证据已经表明，这些疾病可能已经影响到许多人群，而本提案的目的是确定持久性有机氯污染物是否会导致这些异常。

DESCRIPTION (provided by applicant): Male reproductive disorders have become an important public-health issue during recent decades: The incidence of testicular cancer has increased and semen quality has decreased, and the incidences of cryptorchidism and hypospadias appear to have increased in certain regions. These conditions are thought to reflect an underlying entity called the testicular dysgenesis syndrome (TDS), with a common origin in fetal life. TDS appears also to be related to other adverse effects, such as decreased birth sex ratios. Although the etiology is uncertain, endocrine disruption is suspected, perhaps due to persistent organochlorine pollutants. Research in this area has been impeded by the relative rarity of some pathologies and because functional assessment of male reproduction is feasible only at adult age, i.e., many years after the initial toxic exposures. We have chosen to carry out a study in the Faroe Islands north of Scotland, where the residents have an increased exposure to suspected endocrine disrupters from traditional marine food, which may include meat and blubber from the pilot whale. Wide exposure intervals are known to exist and appear independent of confounders in this rather homogeneous community. In Faroese adults, an estimate of prenatal exposure levels can be obtained from the mother's dietary habits and current serum concentration of persistent organochlorine substances. The study will therefore examine reproductive outcomes thought to be associated with endocrine disruption and the TDS. These will include measures of semen quality, ratio of X/Y chromosome-bearing sperm, chromatin stability of the sperm, sex ratio of births, and waiting time to pregnancy. The study will include 400 pregnant couples whose mothers are also invited to participate. Because the men of the pregnant couples constitute a selected population (about 250 are expected to provide a semen sample), we will also examine semen quality parameters in 250 young men from the general population (aged 20-24 years) as well as their exposures. This study therefore aims at providing evidence whether increased exposure to endocrine disrupters, whether from postnatal sources or from prenatal exposure caused by maternal seafood consumption, is associated with reproductive abnormalities in both men and women. Decreased sperm quality, decreased fertility, and decreased sex ratio are reproductive outcomes of substantial public health interest. Current evidence already suggests that these pathologies may already affect many populations, and the present proposal aims at identifying whether persistent organochlorine pollutants contribute to these abnormalities.