Insights into the Development of the Adult Leydig Cell Lineage from Stem Leydig Cells

Abstract

Adult Leydig cells (ALCs) are the steroidogenic cells in the testes that produce testosterone. ALCs develop postnatally from a pool of stem cells, referred to as stem Leydig cells (SLCs). SLCs are spindle-shaped cells that lack steroidogenic cell markers, including luteinizing hormone (LH) receptor and 3β-hydroxysteroid dehydrogenase. The commitment of SLCs into the progenitor Leydig cells (PLCs), the first stage in the lineage, requires growth factors, including Dessert Hedgehog (DHH) and platelet-derived growth factor-AA. PLCs are still spindle-shaped, but become steroidogenic and produce mainly androsterone. The next transition in the lineage is from PLC to the immature Leydig cell (ILC). This transition requires LH, DHH, and androgen. ILCs are ovoid cells that are competent for producing a different form of androgen, androstanediol. The final stage in the developmental lineage is ALC. The transition to ALC involves the reduced expression of 5α-reductase 1, a step that is necessary to make the cells to produce testosterone as the final product. The transitions along the Leydig cell lineage are associated with the progressive down-regulation of the proliferative activity, and the up-regulation of steroidogenic capacity, with each step requiring unique regulatory signaling.

Tcf21+mesenchymal cells contribute to testis somatic cell development, homeostasis, and regeneration

“…In support of this possibility, we show that allogenic Tcf21+ cell transplants or resident Tcf21+ within the testis can be activated to support tissue regeneration and replenish somatic cells in the aging testis. To date there have been several proposed putative stem Leydig cell populations have been described in fetal and early postnatal testis, which are demarcated by expression of diverse cell surface markers that are often species specific, like CD90 for rat and CD51 for mouse (reviewed in Chen et al, 2020;Stanley et al, 2012;Ye et al, 2017). Furthermore, recent data suggests that these stem cell exhibit species specific properties.…”

Widespread transcriptional scanning in the testis modulates gene evolution rates

“…CSF1, CYP11A1 and IGF1 [60][61][62] elongating spermatids, condensing spermatids and condensed spermatids. Based on the main spermatogenic stages, a more detailed spermatogenesis staging were defined by hierarchical clustering to increase resolution.…”

Fibroblast growth factor homologous factor 1 stimulates Leydig cell regeneration from stem cells in male rats

“…Adult Leydig cells (ALCs) are the testicular testosterone (T)‐producing cells, which play a vital role in the male reproductive system. The postnatal development of ALCs is required for the initiation and maintenance of spermatogenesis as well as for the promotion of the male secondary sexual characteristics . ALCs are derived from stem Leydig cells (SLCs), which exist near peritubular myoid cells .…”

“…The postnatal development of ALCs is required for the initiation and maintenance of spermatogenesis as well as for the promotion of the male secondary sexual characteristics . ALCs are derived from stem Leydig cells (SLCs), which exist near peritubular myoid cells . SLCs are spindle‐shaped cells and they differentiate into ALCs when ALCs wear off .…”

“…(LH) receptor (LHCGR) for receiving LH trophic stimulation and express cholesterol transport proteins, high-density lipoprotein receptor (SCARB1) and steroidogenic acute regulatory protein (STAR), as well as steroidogenic enzymes, including cytochrome P450 cholesterol side chain cleavage enzyme (CYP11A1), 3β-hydroxysteroid dehydrogenase isoform 1 (HSD3B1), cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17A1) and 17β-hydroxysteroid dehydrogenase isoform 3 (HSD17B3). 1 ALCs also secrete insulin-like 3 to regulate spermatogenesis. 6 The LC regeneration is very similar to the LC developmental process during puberty.…”