Expression of the p63 and Notch Signaling Systems in Rat Testes During Postnatal Development: Comparison With Their Expression Levels in the Epididymis and Vas Deferens

Abstract

: The role of tubular structures that contribute to the passage of spermatozoa is not solely passive; these structures actively contribute to their own functions, although these tubules and ducts are contiguous and collaborate in the development of the male gamete along their lengths. The testis has the specific function to generate spermatozoa and spermatozoa undergo numerous changes as they pass through the epididymis. A member of the p53 family of genes, p63, is highly expressed in the basal layers of epithelial tissues and plays a key role in maintaining their cell populations, whereas Notch 1 and its ligand Jagged 2 have an important role in the differentiation of germ cells and Jagged 2 is up‐regulated by TAp63, one of the p63 isoforms, which transactivates p53 target genes and induces apoptosis. Although the presence of p63 in most epithelia is established, the role of p63 and its possible relationship with the Notch system in the seminiferous epithelium have not been examined. Therefore, we investigated the expression of p63, Jagged 2, and Notch 1 in the testis during postnatal development in comparison with their expression levels in the vaso‐epididymal epithelium. In the testis, the expression of TAp63 mRNA increased at day 14 after birth and the expressions of Jagged 2 and Notch 1 mRNA increased at day 16 after birth, suggesting that TAp63‐mediated Jagged 2 induction activates the Notch signaling system. On the other hand, the strong signal of ΔNp63 mRNA was already recognized in the vas deferens at day 0 after birth and advanced chronologically along the duct to the caput epididymis and p63 protein was expressed in basal cells in their epithelium, whereas the mRNAs of Jagged 2 and Notch 1 were maintained at a low level. Consequently, examination of our data raises the probability that TAp63 has an important role for maintenance of germ cell numbers, triggering or balancing the development, differentiation, and apoptosis of germ cells in the testis, which is completely different from the role of ΔNp63 in other epithelial tissues.

Neonatal treatment of rats with diethylstilboestrol (DES) induces stromal-epithelial abnormalities of the vas deferens and cauda epididymis in adulthood following delayed basal cell development

“…3E, C, J and N) which persisted into adulthood (Fig. 2); these findings are consistent with those reported by Hayashi et al (2004). In addition to the continuous layer of basal cells in the proximal and distal vas deferens, CK-HMW/p63 immunopositive cells also appeared in the proximal cauda between days 10 and 18 but they did not form a continuous layer (Fig.…”

Combined Vhlh and Pten Mutation Causes Genital Tract Cystadenoma and Squamous Metaplasia

“…p63 exists as two isoforms, ⌬Np63 and TAp63, that are generated by alternate promoters. ⌬Np63 is the isoform that is expressed in basal cells in genital tract epithelia (13,36) and has been shown to be necessary for the development of epithelial tissues (42). Consistent with these findings, real-time PCR analysis demonstrated that ⌬Np63, not TAp63, is the isoform that is expressed by the expanded pool of basal cells in (Fig.…”

“…Pseudostratified epithelia of the genitourinary tract, including the epididymal tubules, vesicular glands, vas deferens, prostate, and urothelium, are lined by a population of p63-expressing basal cells (13,36). While the functions of basal cells are incompletely characterized for most tissues, detailed studies of the prostate have shown that basal cells act as progenitor cells that are necessary for prostatic development (10).…”

Why are epididymal tumours so rare?

“…8 KLF4 is highly expressed by the whole epithelium of the epididymis of the mouse. 9 Notch1 mRNA is in all epididymal regions, without cellular identity; 10 Notch1 is only detectable by in situ hybridisation in hyperplastic epididymal epithelial cells of constitutively active Notch1-transgenic mice. 11 These embryonic stem cell factors may have other functions, such as cellular differentiation, in the adult epididymis.…”