De França L R, Hess R A, Cooke P S, Russell L D
Department of Morphology, Federal University of Minas Gerais, Brazil.
Anat Rec. 1995 May;242(1):57-69. doi: 10.1002/ar.1092420108.
The testes of rats treated neonatally with propylthiouracil (PTU) grow to almost twice their normal size. The cause of testicular enlargement has been suggested to be the result of delayed maturation of Sertoli cells, allowing Sertoli cell division to occur beyond the 15th postnatal day, the commonly recognized cutoff date for Sertoli cell divisions. It has been shown that an increased population of Sertoli cells in postnatal development supports increased numbers of germ cells in adult animals. After examining developing rats treated neonatally with PTU, we hypothesized that an approximate 10-day delay in maturation was occurring and proceeded to test this hypothesis experimentally. Thus the purpose of this report was to determine if a 10-day delay in maturation could explain the increased numbers of Sertoli cells and increased testis size in PTU-treated animals.
Both control animals and animals treated neonatally with PTU N = 5/group were sacrificed at 15 and 25 days of age and prepared for electron microscopy.
Micrographs show and morphometric ultrastructural analysis of numerous parameters demonstrated at the 95% probability level that Sertoli cells from 25-day-old PTU animals are not different in size and most constituents (volume and surface area) from 15-day-old control animals and are less mature than 25-day-old control animals. Mitosis of Sertoli cells was observed in PTU-treated animals in 25-day-old animals but not in age-matched controls. The number of Sertoli cells in 25-day-old PTU-treated animals is significantly increased over age-matched controls. Micrographs show the presence of immature Sertoli cell nuclei in 25-day-old animals receiving PTU as well as increased germ cell degeneration in this group. Sertoli cell tight junction formation is also delayed in PTU-treated animals as compared with controls.
Together, the data show that delayed maturation of Sertoli cells occurs in treated animals that corresponds to a minimum of 10 developmental days. In the immature state, Sertoli cells continue to divide. Data presented herein and published data related to PTU treatment indicate that delayed maturation of the Sertoli cell results in delayed maturation and proliferation of other testicular cell types. From this and from published data, the hypothesis is presented that the Sertoli cell is responsible for the overall control of testis development.
新生期用丙硫氧嘧啶（PTU）处理的大鼠睾丸生长至正常大小的近两倍。睾丸增大的原因被认为是支持细胞成熟延迟的结果，使得支持细胞分裂发生在出生后第15天之后，而第15天是公认的支持细胞分裂截止日期。研究表明，出生后发育过程中支持细胞数量增加可支持成年动物中生殖细胞数量的增加。在检查新生期用PTU处理的发育中大鼠后，我们假设成熟过程大约延迟了10天，并着手通过实验验证这一假设。因此，本报告的目的是确定成熟延迟10天是否可以解释PTU处理动物中支持细胞数量增加和睾丸增大的现象。
对照组动物和新生期用PTU处理的动物（每组N = 5）在15日龄和25日龄时处死，并制备用于电子显微镜检查的样本。
显微照片显示，对众多参数进行的形态计量超微结构分析在95%概率水平上表明，25日龄PTU处理动物的支持细胞在大小和大多数成分（体积和表面积）上与15日龄对照动物无异，且比25日龄对照动物成熟度低。在25日龄的PTU处理动物中观察到支持细胞有丝分裂，但在年龄匹配的对照动物中未观察到。25日龄PTU处理动物的支持细胞数量比年龄匹配的对照动物显著增加。显微照片显示，接受PTU的25日龄动物中存在未成熟的支持细胞核，且该组中生殖细胞变性增加。与对照组相比，PTU处理动物的支持细胞紧密连接形成也延迟。
综合来看，数据表明在处理过的动物中发生了支持细胞成熟延迟，相当于至少10个发育日。在未成熟状态下，支持细胞继续分裂。本文呈现的数据以及与PTU处理相关的已发表数据表明，支持细胞成熟延迟导致其他睾丸细胞类型成熟和增殖延迟。基于此以及已发表的数据，提出了支持细胞负责睾丸发育总体调控的假设。
