Kleymenova Elena, Swanson Cynthia, Boekelheide Kim, Gaido Kevin W
CIIT Centers for Health Research, Research Triangle Park, North Carolina 27709, USA.
Biol Reprod. 2005 Sep;73(3):482-90. doi: 10.1095/biolreprod.104.037184. Epub 2005 May 18.
Di(n-butyl) phthalate (DBP) is commonly used in personal care products and as a plasticizer to soften consumer plastic products. Male rats exposed to DBP in utero have malformations of the male reproductive tract and testicular atrophy characterized by degeneration of seminiferous epithelium and decreased sperm production. In the fetal testis, in utero exposure to DBP reportedly resulted in reduced testosterone levels, Leydig cell aggregates, and multinucleated gonocytes (MNG). We investigated whether exposure in utero to DBP affects rat fetal Sertoli cells and compromises interactions between Sertoli and germ cells in the developing testis. Histological examination showed that MNG occurred at low frequency in the normal fetal rat testis. Exposure in utero at the dose level of DBP above estimated environmental or occupational human exposure levels significantly increased the number of these abnormal germ cells. Postnatally, MNG exhibited aberrant mitoses and were detected at the basal lamina. MNG were not apoptotic in the fetal and postnatal rat testes, as indicated by TUNEL. Sertoli cells in DBP-exposed fetal testis had retracted apical processes, altered organization of the vimentin cytoskeleton, and abnormal cell-cell contacts with gonocytes. The effect of DBP on Sertoli cell morphology at the level of light microscopy was reversed after birth and cessation of exposure. Our data indicate that fetal Sertoli cells are targeted by exposure in utero to DBP and suggest that abnormal interactions between Sertoli and germ cells during fetal life play a role in the development of MNG.
邻苯二甲酸二丁酯（DBP）常用于个人护理产品中，并作为增塑剂来软化消费塑料制品。在子宫内接触DBP的雄性大鼠会出现雄性生殖道畸形和睾丸萎缩，其特征为生精上皮变性和精子生成减少。据报道，在胎儿睾丸中，子宫内接触DBP会导致睾酮水平降低、睾丸间质细胞聚集以及多核生殖母细胞（MNG）的出现。我们研究了子宫内接触DBP是否会影响大鼠胎儿的支持细胞，并损害发育中睾丸内支持细胞与生殖细胞之间的相互作用。组织学检查显示，正常胎儿大鼠睾丸中MNG的出现频率较低。在高于估计的环境或职业性人类接触水平的DBP剂量下进行子宫内接触，会显著增加这些异常生殖细胞的数量。出生后，MNG表现出异常有丝分裂，并在基膜处被检测到。TUNEL检测表明，MNG在胎儿和出生后大鼠睾丸中均未发生凋亡。接触DBP的胎儿睾丸中的支持细胞顶端突起回缩，波形蛋白细胞骨架的组织发生改变，并且与生殖母细胞的细胞间接触异常。出生后停止接触后，DBP对支持细胞形态在光学显微镜水平上的影响得到逆转。我们的数据表明，胎儿支持细胞是子宫内接触DBP的靶细胞，并提示胎儿期支持细胞与生殖细胞之间的异常相互作用在MNG的发生发展中起作用。
