Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; International Center for Research & Training in Endocrine Disruption of Male Reproduction & Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; International Center for Research & Training in Endocrine Disruption of Male Reproduction & Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Sci Total Environ. 2023 May 1;871:161914. doi: 10.1016/j.scitotenv.2023.161914. Epub 2023 Jan 31.
Phthalate exposure during fetal life may disrupt testicular development. Congruent with this, studies have found shorter anogenital distance, reduced penile size and altered hormone levels in infant boys whose mothers were exposed to higher levels of some phthalates during pregnancy. Few studies have explored if such adverse effects persist in adulthood. Thus, we aimed to explore if there is an association between fetal phthalate exposure and markers of testicular function in young adult men.
In a longitudinal mother-child cohort from Copenhagen, Denmark, we examined 100 young men whose mothers during pregnancy had serum drawn and analyzed for 34 phthalate metabolites. Examinations of the young men took place at 18-20 years of age and included measurements of adult markers of testicular function (reproductive hormones, penile size, anogenital distance (AGD), testis volume, semen quality) and growth factors. Associations between maternal serum concentrations of phthalate metabolites and reproductive measures in the young men were tested using multiple linear regression.
Most consistently, higher maternal phthalate exposure was associated with higher luteinizing hormone (LH) but unchanged testosterone in adult sons. Congruently, higher maternal exposure was associated with lower total and free testosterone/LH ratios in adult sons. For example, twice as high maternal MiNP was associated with a 7.9 % (95 % CI 1.6-13.8) lower free testosterone/LH ratio. There was no consistent pattern of associations between the different phthalate metabolites and other reproductive hormones, clinical outcomes, or semen quality. None of the tested associations was significant after multiplicity adjustment.
In this exploratory study, higher maternal exposure to some phthalates was associated with impaired testicular Leydig cell function evidenced by a lower total and free testosterone/LH ratio in adult sons. This unique 18-20-year follow-up study raises concern and suggests that exposure of pregnant women to phthalates may have long-term effects on adult reproductive health in male offspring.
胎儿期邻苯二甲酸酯暴露可能会破坏睾丸发育。与此一致的是，研究发现，母亲在怀孕期间接触较高水平的某些邻苯二甲酸酯的婴儿男孩的肛殖距较短、阴茎尺寸较小且激素水平改变。少数研究探索了这种不利影响是否会持续到成年期。因此，我们旨在探讨胎儿邻苯二甲酸酯暴露与年轻成年男性睾丸功能标志物之间是否存在关联。
在丹麦哥本哈根的一项纵向母子队列研究中，我们检查了 100 名年轻男性，他们的母亲在怀孕期间采集了血清并进行了 34 种邻苯二甲酸酯代谢物的分析。这些年轻男性在 18-20 岁时接受了检查，包括测量成年睾丸功能标志物（生殖激素、阴茎尺寸、肛殖距（AGD）、睾丸体积、精液质量）和生长因子。使用多元线性回归检验母亲血清中邻苯二甲酸酯代谢物浓度与年轻男性生殖指标之间的关联。
最一致的是，母亲较高的邻苯二甲酸酯暴露与成年儿子的黄体生成素（LH）升高但睾酮不变相关。一致的是，母亲较高的暴露与成年儿子的总睾酮和游离睾酮/LH 比值降低相关。例如，母亲 MiNP 增加一倍与游离睾酮/LH 比值降低 7.9%（95%CI 1.6-13.8）相关。不同邻苯二甲酸酯代谢物与其他生殖激素、临床结局或精液质量之间没有一致的关联模式。在多重调整后，没有一项测试关联具有统计学意义。
在这项探索性研究中，母亲较高的邻苯二甲酸酯暴露与成年儿子睾丸间质细胞功能受损相关，表现为总睾酮和游离睾酮/LH 比值降低。这项独特的 18-20 岁随访研究引起了关注，并表明孕妇接触邻苯二甲酸酯可能对男性后代的成年生殖健康产生长期影响。
