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Progenitor cells of the testosterone-producing Leydig cells revealed.

Davidoff MS, Middendorff R, Enikolopov G, Riethmacher D, Holstein AF, Müller D - J. Cell Biol. (2004)

Bottom Line: Their origin during ontogeny and regeneration processes is still a matter of debate.Here, we show that cells of testicular blood vessels, namely vascular smooth muscle cells and pericytes, are the progenitors of Leydig cells.Resembling stem cells of the nervous system, the Leydig cell progenitors are characterized by the expression of nestin.

View Article: PubMed Central - PubMed

Affiliation: Institute of Anatomy, University of Hamburg, Germany. davidoff@uke.uni-hamburg.de

ABSTRACT
The cells responsible for production of the male sex hormone testosterone, the Leydig cells of the testis, are post-mitotic cells with neuroendocrine characteristics. Their origin during ontogeny and regeneration processes is still a matter of debate. Here, we show that cells of testicular blood vessels, namely vascular smooth muscle cells and pericytes, are the progenitors of Leydig cells. Resembling stem cells of the nervous system, the Leydig cell progenitors are characterized by the expression of nestin. Using an in vivo model to induce and monitor the synchronized generation of a completely new Leydig cell population in adult rats, we demonstrate specific proliferation of vascular progenitors and their subsequent transdifferentiation into steroidogenic Leydig cells which, in addition, rapidly acquire neuronal and glial properties. These findings, shown to be representative also for ontogenetic Leydig cell formation and for the human testis, provide further evidence that cellular components of blood vessels can act as progenitor cells for organogenesis and repair.

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EDS exposure induces testicular nestin expression, localized to VSMCs and PCs. (a) Immunoblots demonstrate increased nestin expression during the period of Leydig cell (see levels of CytP450) depletion. (b–d) Immunohistochemical analyses show that nestin is localized to vascular smooth muscle cells (VSMC) and pericytes (PC) (d), but not to endothelial cells (EC; see b and c, with longitudinal orientation) of testicular blood vessels. (e) VSMCs and PCs are stained for smooth muscle α-actin (SMA). (f–h) At d 2 after EDS, VSMCs and PCs proliferate as indicated by nuclear incorporation of BrdU (f and h). The testicular distribution of nestin immunoreactivity at that time, localized to large intertubular as well as to peritubular (arrows) vessels, is shown in g. Higher magnification of an area corresponding to the box marked in g demonstrates proliferating (BrdU labeled) cells of the peritubular microvasculature (h, arrows). Note that some spermatogonia (arrowheads) are also detectable. The lumen of a blood vessel filled with erythrocytes is marked by an asterisk. T, seminiferous tubules.
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fig2: EDS exposure induces testicular nestin expression, localized to VSMCs and PCs. (a) Immunoblots demonstrate increased nestin expression during the period of Leydig cell (see levels of CytP450) depletion. (b–d) Immunohistochemical analyses show that nestin is localized to vascular smooth muscle cells (VSMC) and pericytes (PC) (d), but not to endothelial cells (EC; see b and c, with longitudinal orientation) of testicular blood vessels. (e) VSMCs and PCs are stained for smooth muscle α-actin (SMA). (f–h) At d 2 after EDS, VSMCs and PCs proliferate as indicated by nuclear incorporation of BrdU (f and h). The testicular distribution of nestin immunoreactivity at that time, localized to large intertubular as well as to peritubular (arrows) vessels, is shown in g. Higher magnification of an area corresponding to the box marked in g demonstrates proliferating (BrdU labeled) cells of the peritubular microvasculature (h, arrows). Note that some spermatogonia (arrowheads) are also detectable. The lumen of a blood vessel filled with erythrocytes is marked by an asterisk. T, seminiferous tubules.

Mentions: To prove and document reliably the known fate of Leydig cells in the rat testis after a single i.p. EDS injection, we monitored the expression of a Leydig cell marker protein, cytochrome P450 side chain cleavage enzyme (CytP450), representing the rate-limiting enzyme of steroidogenesis. CytP450-immunoreactive cells completely disappeared 3 d after EDS treatment and began to reappear ∼14 d after EDS treatment, detectable primarily as cell clusters located in the vicinity of intertubular vessels (Fig. 1 a) and in form of single, peritubularly distributed spindle-shaped cells (Fig. 1 b). At this time, the total amount of Leydig cells is still very low (Fig. 1 c), and the expression of CytP450 is not yet detectable by immunoblotting (see Fig. 2 a).


Progenitor cells of the testosterone-producing Leydig cells revealed.

Davidoff MS, Middendorff R, Enikolopov G, Riethmacher D, Holstein AF, Müller D - J. Cell Biol. (2004)

EDS exposure induces testicular nestin expression, localized to VSMCs and PCs. (a) Immunoblots demonstrate increased nestin expression during the period of Leydig cell (see levels of CytP450) depletion. (b–d) Immunohistochemical analyses show that nestin is localized to vascular smooth muscle cells (VSMC) and pericytes (PC) (d), but not to endothelial cells (EC; see b and c, with longitudinal orientation) of testicular blood vessels. (e) VSMCs and PCs are stained for smooth muscle α-actin (SMA). (f–h) At d 2 after EDS, VSMCs and PCs proliferate as indicated by nuclear incorporation of BrdU (f and h). The testicular distribution of nestin immunoreactivity at that time, localized to large intertubular as well as to peritubular (arrows) vessels, is shown in g. Higher magnification of an area corresponding to the box marked in g demonstrates proliferating (BrdU labeled) cells of the peritubular microvasculature (h, arrows). Note that some spermatogonia (arrowheads) are also detectable. The lumen of a blood vessel filled with erythrocytes is marked by an asterisk. T, seminiferous tubules.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172461&req=5

fig2: EDS exposure induces testicular nestin expression, localized to VSMCs and PCs. (a) Immunoblots demonstrate increased nestin expression during the period of Leydig cell (see levels of CytP450) depletion. (b–d) Immunohistochemical analyses show that nestin is localized to vascular smooth muscle cells (VSMC) and pericytes (PC) (d), but not to endothelial cells (EC; see b and c, with longitudinal orientation) of testicular blood vessels. (e) VSMCs and PCs are stained for smooth muscle α-actin (SMA). (f–h) At d 2 after EDS, VSMCs and PCs proliferate as indicated by nuclear incorporation of BrdU (f and h). The testicular distribution of nestin immunoreactivity at that time, localized to large intertubular as well as to peritubular (arrows) vessels, is shown in g. Higher magnification of an area corresponding to the box marked in g demonstrates proliferating (BrdU labeled) cells of the peritubular microvasculature (h, arrows). Note that some spermatogonia (arrowheads) are also detectable. The lumen of a blood vessel filled with erythrocytes is marked by an asterisk. T, seminiferous tubules.
Mentions: To prove and document reliably the known fate of Leydig cells in the rat testis after a single i.p. EDS injection, we monitored the expression of a Leydig cell marker protein, cytochrome P450 side chain cleavage enzyme (CytP450), representing the rate-limiting enzyme of steroidogenesis. CytP450-immunoreactive cells completely disappeared 3 d after EDS treatment and began to reappear ∼14 d after EDS treatment, detectable primarily as cell clusters located in the vicinity of intertubular vessels (Fig. 1 a) and in form of single, peritubularly distributed spindle-shaped cells (Fig. 1 b). At this time, the total amount of Leydig cells is still very low (Fig. 1 c), and the expression of CytP450 is not yet detectable by immunoblotting (see Fig. 2 a).

Bottom Line: Their origin during ontogeny and regeneration processes is still a matter of debate.Here, we show that cells of testicular blood vessels, namely vascular smooth muscle cells and pericytes, are the progenitors of Leydig cells.Resembling stem cells of the nervous system, the Leydig cell progenitors are characterized by the expression of nestin.

View Article: PubMed Central - PubMed

Affiliation: Institute of Anatomy, University of Hamburg, Germany. davidoff@uke.uni-hamburg.de

ABSTRACT
The cells responsible for production of the male sex hormone testosterone, the Leydig cells of the testis, are post-mitotic cells with neuroendocrine characteristics. Their origin during ontogeny and regeneration processes is still a matter of debate. Here, we show that cells of testicular blood vessels, namely vascular smooth muscle cells and pericytes, are the progenitors of Leydig cells. Resembling stem cells of the nervous system, the Leydig cell progenitors are characterized by the expression of nestin. Using an in vivo model to induce and monitor the synchronized generation of a completely new Leydig cell population in adult rats, we demonstrate specific proliferation of vascular progenitors and their subsequent transdifferentiation into steroidogenic Leydig cells which, in addition, rapidly acquire neuronal and glial properties. These findings, shown to be representative also for ontogenetic Leydig cell formation and for the human testis, provide further evidence that cellular components of blood vessels can act as progenitor cells for organogenesis and repair.

Show MeSH
Related in: MedlinePlus