Changes in the Testis Interstitium of Sprague Dawley Rats from Birth to Sexual Maturity1

Abstract

Changes in the rat testis interstitium from birth to adulthood were studied using Sprague Dawley rats of 1, 7, 14, 21, 28, 40, 60, and 90 days of age. Our objectives were 1) to understand the fate of the fetal Leydig cells (FLC) in the postnatal rat testis, 2) to determine the volume changes in testicular interstitial components and testicular steroidogenic capacity in vitro with age, 3) to differentially quantify FLC, adult Leydig cells (ALC), and different connective tissue cell types by number and average volume, and 4) to investigate the relationship between mesenchymal and ALC numbers during testicular development. FLC were present in rat testes from birth to 90 days, and they were the only steroidogenic cells in the testis interstitium at Days 1 and 7. Except for FLC, all other interstitial cell numbers and volumes increased from birth to 90 days. The average volume of an FLC and the absolute volume of FLC per testis were similar at all ages except at Day 21, when lower values were observed for both parameters. FLC number per testis remained constant from birth through 90 days. The observations suggested that the significance of FLC in the neonatal-prepubertal rat testis is to produce testosterone to activate the hypothalamo-hypophyseal-testicular axis for the continued development of the male reproductive system. ALC were the abundant Leydig cell type by number and absolute volume per testis from Day 14 onwards. The absolute numbers of ALC and mesenchymal cells per testis increased linearly from birth to 90 days, with a slope ratio of 2:1, respectively, indicating that the rate of production of Leydig cells is 2-fold greater than that of mesenchymal cells in the postnatal rat testis through 90 days. In addition, this study showed that the mesenchymal cells are an active cell population during testis development and that their numbers do not decrease but increase with Leydig cell differentiation and testicular growth up to sexual maturity (90 days).

Fetal programming of adult Leydig cell function by androgenic effects on stem/progenitor cells

“…It is unclear if the complete population of COUP-TFII-expressing stem cells can develop into adult Leydig cells or only a subpopulation, because only a proportion of the stem cells switched on GATA4 or PDGFRα after EDS. Previous studies suggested that adult Leydig cells could originate from other interstitial cell types, such as peritubular myoid cells, pericytes, endothelial cells, or macrophages (24,29,(54)(55)(56). Using specific markers for these cell types and the EDS model, we found no evidence for coexpression of COUP-TFII in these cell types.…”

Steroidogenesis and steroidogenic gene expression in postnatal fetal rat Leydig cells

“…However, several studies suggested that PFLCs do not all enter apoptosis and degenerate but can persist in later puberty (Kerr and Knell, 1988;Ariyaratne and Chamindrani Mendis-Handagama, 2000;Ivell et al, 2003). Thus, the fate, function and the regulation of PFLCs after birth are still unknown, while testosterone production by PFLCs The present study has demonstrated a role for the cAMP-PKA transduction pathway in the regulation of Leydig-cell specific genes in PFLCs.…”

Key factors in the regulation of fetal and postnatal leydig cell development

“…Early work suggested that fetal Leydig cells decline in number after birth due to either dedifferentiation or apoptotic cell death (Tapanainen et al, 1984;Byskov, 1986). Other studies have shown that the total number of the cells in the testis does not change markedly, but the number of Leydig cells per unit volume of testis decreases (Kerr and Knell, 1988;Ariyaratne and Chamindrani Mendis-Handagama, 2000). Whether, Leydig cell numbers are static or decline, androgen production decreases dramatically as the fetal Leydig cells undergo functional dedifferentiation starting in late gestation (Migrenne et al, 2001).…”