How do you get six meters of epididymis inside a human scrotum?

It is very clear that the epididymis plays a crucial role in the maturation of spermatozoa, and without a fully developed and functional epididymis, male infertility will result. We are especially interested in understanding the mechanisms that regulate the development of this important organ because disruptions to epididymal function will also arise as a consequence of abnormal development. Very little is known either of the process of epididymal development or the nature and causes of congenital defects that lead to male infertility. A major event during Wolffian/epididymal duct embryonic development is elongation and coiling and this short review outlines potential mechanisms by which these events occur. It is hypothesized that elongation is the result of cell proliferation coupled with directed cell rearrangements, the later regulated by the planar cell polarity signaling pathway. Coiling proceeds in a proximal to distal manner, with three-dimensional coiling beginning approximately embryonic day 16.5 to 18.5 in the mouse. The exact mechanisms of coiling are not known but we hypothesize that it involves an interaction between the Wolffian duct epithelium and the surrounding mesenchyme cells, such that the extracellular matrix is remodeled to allow coiling and growth of the duct. Cell proliferation in the Wolffian duct appears to be dependent on the presence of androgens and mesenchymal factors during embryonic development, but lumicrine factors play an additional role during postnatal development.

Gene expression in the efferent ducts, epididymis, and vas deferens during embryonic development of the mouse.

The tissues of the male reproductive tract are characterized by distinct morphologies, from highly coiled to un-coiled. Global gene expression profiles of efferent ducts, epididymis, and vas deferens were generated from embryonic day 14.5 to postnatal day 1 as tissue-specific morphologies emerge. Expression of homeobox genes, potential mediators of tissue-specific morphological development, was assessed. Twenty homeobox genes were identified as either tissue-enriched, developmentally regulated, or both. Additionally, ontology analysis demonstrated cell adhesion to be highly regulated along the length of the reproductive tract. Regulators of cell adhesion with variable expression between the three tissues were identified including Alcam, various cadherins, and multiple integrins. Immunofluorescence localization of the cell adhesion regulators POSTN and CDH2 demonstrated cell adhesion in the epithelium and mesenchyme of the epididymis may change throughout development. These results suggest cell adhesion may be modulated in a tissue-specific manner, playing an important role in establishing each tissue's final morphology.

Expression of the Ladybird-like homeobox 2 transcription factor in the developing mouse testis and epididymis.

BACKGROUND: Homeoproteins are a class of transcription factors that are well-known regulators of organogenesis and cell differentiation in numerous tissues, including the male reproductive system. Indeed, a handful of homeoproteins have so far been identified in the testis and epididymis where a few were shown to play important developmental roles. Through a degenerate PCR approach aimed at identifying novel homeoproteins expressed in the male reproductive system, we have detected several homeoproteins most of which had never been described before in this tissue. One of these homeoproteins is Ladybird-like homeobox 2 (Lbx2), a homeobox factor mostly known to be expressed in the nervous system. RESULTS: To better define the expression profile of Lbx2 in the male reproductive system, we have performed in situ hybridization throughout testicular and epididymal development and into adulthood. Lbx2 expression was also confirmed by real time RT-PCR in those tissues and in several testicular and epididymal cell lines. In the epididymis, a highly segmented tissue, Lbx2 shows a regionalized expression profile, being more expressed in proximal segments of the caput epididymis than any other segment. In the testis, we found that Lbx2 is constitutively expressed at high levels in Sertoli cells. In interstitial cells, Lbx2 is weakly expressed during fetal and early postnatal life, highly expressed around P32-P36, and absent in adult animals. Finally, Lbx2 can also be detected in a population of germ cells in adults. CONCLUSION: Altogether, our data suggest that the homeoprotein Lbx2 might be involved in the regulation of male reproductive system development and cell differentiation as well as in male epididymal segmentation.

Sonic hedgehog pathway genes are expressed and transcribed in the adult mouse epididymis.

One role of the hedgehog (hh) signaling pathway during development is to assist in establishing pattern orientation in the embryo. The structure and function in the adult epididymis is highly patterned, and since the sonic hedgehog (Shh) pathway is known to be functional in the developing male tract and the expression of other pattern-influencing genes has recently been found in the adult epididymis, we have examined the adult mouse epididymis for Shh pathway molecules. Examination was at both the gene and protein level. Shh, the secreted signal molecule, patched (Ptc), its membrane receptor, and Gli-1, a downstream transcription factor, were detected at the gene level with semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and at the protein level with Western blot analysis. Immunohistochemical localization further detected Shh specifically in the epididymal epithelium. It was hypothesized that efferent duct ligation (EDL) would alter epididymal segmentation within 30 days of the ligation, especially in the proximal segments of the caput epididymis. It was further hypothesized that these alterations would be correlated with changes in the expression of genes in the Shh pathway. EDL did not alter epididymal segmentation, but Shh, Ptc, and Gli1 expression was significantly altered at specific times after the ligation. The presence of the signaling pathway in the adult epididymis is a novel finding, as is the fact that in the distal epididymis, the specific gene expressions are altered by EDL. This suggests that the genes are capable of being regulated in a manner that is influenced by testicular contribution, and it implies that those genes have a function in the epididymis subject to that regulation.

5' hox genes and meis 1, a hox-DNA binding cofactor, are expressed in the adult mouse epididymis.

Hox genes determine the formation of segmented structures during development. The epididymis shows a segmented organization in its structure and function beyond embryogenesis. This study examined the adult mouse epididymis and vas deferens for expression of 5' hox genes and a hox-DNA binding cofactor. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed the expression of hoxa-9, hoxa-10, hoxa-11, hoxd-9, and hoxd-10 in all regions including the vas deferens. Semiquantitative RT-PCR revealed highest mRNA levels for hoxa-11 in the distal part of the epididymis and vas deferens, and this was confirmed by Northern blot analysis. To determine protein presence an antibody raised against a peptide N-terminal to the homeodomain of hoxa-11 was produced in rabbits. The antibody recognized a band of approximately 37-39 kDa in Western blot analysis. Immunohistochemistry indicated the presence of hoxa-11 in the nuclei of the epithelial cells with some staining in the cytoplasm. Staining was also detected in nuclei of interstitial cells throughout the entire organ and the vas deferens. A DNA binding cofactor for hoxa-11, Meis 1, was investigated for its presence in the epididymis. Semiquantitative RT-PCR identified both transcripts for Meis 1 (Meis 1a and Meis 1b) in all regions. Protein presence was confirmed by Western blot analysis, and this detected one band of approximately 53-55 kDa. Immunohistochemistry localized Meis 1 in the nuclei of interstitial cells throughout the entire organ and the vas deferens. Our study provides preliminary data from which we suggest the involvement of homeodomain transcription factors in the maintenance of segmental function of the adult epididymis and vas deferens.