Growth Factor-Stimulated Mitogen-Activated Kinase (MAPK) Phosphorylation in the Rat Epididymis Is Limited by Segmental Boundaries1

Abstract

Previous evidence has shown that sperm maturation is the result of successive events that influence sperm cells as they move through different microenvironments from the caput to the cauda epididymis. The physiological basis for the creation and maintenance of specific microenvironments along the epididymis are poorly understood. Anatomically, the epididymis consists of segments or lobules of epididymal tubule separated by connective tissue septa (CTS). The fact that CTS restrict the diffusion of tracer substances between segments and that certain gene expression patterns are segment-specific suggest that segments may represent functional epididymal units. In this report, we have further investigated epididymal segmentation by focusing on the ability of CTS to limit the effect of biologically relevant molecules, in particular epidermal growth factor (EGF), basic fibroblast growth factor (FGF2), and vascular endothelial growth factor A (VEGFA), in Segments 1 and 2 of the rat epididymis. We have demonstrated that these growth factors activate mitogen-activated kinase (MAPK) in both segments studied and that growth factors injected into the interstitial space of these segments in vivo exhibited a stimulatory effect only in the segment into which they were injected, i.e., MAPK activation was not observed in the adjacent segment. This restricting influence of CTS was abrogated by treatment with collagenase. In addition, we demonstrate the expression of selected forms of these growth factors and their receptors in Segments 1 and 2, and identify potential downstream targets. These results suggest that CTS regulate the trophic influences of growth factors and potentially other paracrine molecules, thus creating functionally separate units within the epididymis.

Deficiency of fibroblast growth factor 2 (FGF‐2) leads to abnormal spermatogenesis and altered sperm physiology

“…Among them, it has been reported that FGF-2 stimulates the activation of Ras/mitogen-activated protein kinase in the first segments of the epididymis. This effect has also been described for other growth factors, such as epidermal growth factor and vascular epidermal growth factor (Tomsig, Usanovic, & Turner, 2006). A report suggests that FGF-2 stimulates the expression of γ-glutamyl transpeptidase, an enzyme that would protect sperm from oxidative stress damage by keeping low levels of glutathione and preventing protein oxidation (Lan et al, 1998).…”

Looking to the Future of Epididymal Research: Why This, Why Now?

“…This is because sperm are stored in the cauda and remain susceptible to toxicant exposure and oxidative stress. Regulation of the epithelium by interstitial factors. Paracrine relationships between peritubular or interstitial cells and epididymal epithelial cells have previously been suggested or implied (Serre and Robaire, 2002; Tomsig et al, 2006; Jiminez‐Trejo et al, 2007). Older evidence showing nuclear androgen localization in rat epididymal interstitial/peritubular cells (Figure) suggests that some extratubular cells in the epididymis are androgen regulated and that their activities may be related to maintenance of normal tubule function or development.…”

Pannexins and Connexins: Their Relevance for Oocyte Developmental Competence

“…Exposure to flutamide induced a decrease of Cx43 expression in the stromal cells of the corpus and cauda regions of boar epididymis (Lydka et al, 2011). Epidermal growth factor (EGF) was suggested to impact epididymal function (Tomsig et al, 2006). It was assumed that in men suffering from azoospermy a decreased expression of EGFR could provoke diminished levels of Cx43 (Dube et al, 2012).…”