Cell Proliferation and Cell Death in Mouse Reproductive Tracts

小鼠生殖道中的细胞增殖和细胞死亡

• 批准号: 07454225
• 负责人: IGUCHI Taisen
• 金额: $ 2.05万
• 依托单位: Yokohama City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07454225/
• 关键词: apoptosis; uterus; pregnancy-dependent mammary tumors; vagina; testis; 前立腺; 副精巣; 乳腺; 脱落膜腫

Apoptosis was encountered mainly in spermatids and spermatocytes in surgically induced bilateral cryptochidism of male mice. Expression of TNF-alpha receptor, TGFbeta2, beta3 and Fas mRNAs increased in the cryptorchid testes within 24 h after the operation. In order to study the mechanism of mammary gland involution, litters were removed on day 20 of lactation and morphological and biochemical changes were examined in GR/A mice and lpr^<cg> mice lacking functional Fas. Apoptotic cell death occurs during involution of mammary gland with the increase of mRNA expression of TNF-alpha and TGF-beta1. TNF-alpha and anti-Fas antibody directly killed more than 80% of mammary cells from p53 knockout mice in vitro within 24 h in the presence of actinomycin D,supporting the hypothesis that Fas and/or TNF-alpha are involved in the induction of apoptosis of mouse mammary glands. Pregnancy-dependent mammary tumors (PDMT) and transplantable PDMT (TPDMT-4), are exceptionally stable in hormone dependence, continue to grow until parturition and regress soon after deliverly. Apoptosis occurs in the regressing PDMT and TPDMT-4 on day 20 or 18 of pregnancy, and on the parturient and the following days, respectively.Perinatal treatment of female mice with diethylstilbestrol (DES) results in estrogen-independent persistent proliferation and cornification of vaginal epithelium. Expression of c-jun and c-fos mRNAs was greater in the vagina of neonatally DES-exposed mice than in controls. Neonatal exposure to DES and tamoxifen induced permanent changes in the pelvis and femur. Rodent uterus and vagina show marked histological changes during the estrous cycle. There is an inverse correlation between cell death and cell proliferation in rat uterine and vaginal epithelial cells during the estrous cycle.

在手术诱导的雄性小鼠双侧隐睾中，凋亡主要发生在精子细胞和精母细胞中。隐睾手术后24 h内TNF-α受体、TGF β 2、TGF β 3和Fas mRNA表达增加。为了研究乳腺退化的机制，在哺乳期第20天取出窝仔，观察功能性Fas缺失的GR/A小鼠和lpr^小鼠的形态学和生化变化<cg>。随着TNF-α和TGF-β 1 mRNA表达的增加，乳腺退化过程中发生细胞凋亡。TNF-α和抗Fas抗体在放线菌素D存在下，在24 h内直接杀死80%以上的p53基因敲除小鼠乳腺细胞，支持Fas和/或TNF-α参与诱导小鼠乳腺细胞凋亡的假设。妊娠依赖性乳腺肿瘤（Pregnancy-dependent mammary tumors，PDMT）和可移植性乳腺肿瘤（transplantable PDMT-4，TPDMT-4）是一种激素依赖性非常稳定的肿瘤，可持续生长至分娩，分娩后可迅速消退。凋亡发生在PDMT和TPDMT-4中，分别发生在妊娠第20天和第18天，以及临产和随后的几天。围产期用己烯雌酚（DES）处理雌性小鼠导致非雌激素依赖的阴道上皮持续增殖和角化。c-jun和c-fos mRNA的表达在暴露于DES的小鼠阴道中比对照组更高。新生儿暴露于DES和他莫昔芬诱导骨盆和股骨的永久性变化。啮齿动物的子宫和阴道在发情周期中表现出明显的组织学变化。在动情周期中，大鼠子宫和阴道上皮细胞的细胞死亡和细胞增殖之间存在负相关。

项目成果

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