Role of p57KIP2 in Stem and Progenitor Leydig Cells of Mouse Testes
Purpose: Precise control of proliferation and differentiation of Leydig cells is important for gonadal androgenesis and spermatogenesis. Though cyclin-dependent kinase inhibitors are crucial for cell proliferation and differentiation, their role in the development of early adult Leydig cells (ALCs...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Korean Society for Sexual Medicine and Andrology
2025-01-01
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| Series: | The World Journal of Men's Health |
| Subjects: | |
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| Summary: | Purpose: Precise control of proliferation and differentiation of Leydig cells is important for gonadal androgenesis and spermatogenesis.
Though cyclin-dependent kinase inhibitors are crucial for cell proliferation and differentiation, their role in the development
of early adult Leydig cells (ALCs) remained unanswered. To understand mechanism for ALC development, functional
expression of p57KIP2 (cdkn1c) was investigated in the stem Leydig cells (SLCs) and progenitor Leydig cells (PLCs) in mice.
Materials and Methods: The roles of p57KIP2 in the proliferation, differentiation, apoptosis, and steroidogenesis in SLCs and
PLCs were investigated by antibodies and bromodeoxyuridine (BrdU) labeling in the early neonatal testes and p57kip2 siRNA
in the isolated SLCs and PLCs. Steroidogenic differentiation of PLCs was examined by progesterone and testosterone production
in cell culture.
Results: From postnatal day (PND) 1 to 14, p57KIP2(+) spindle-shaped cells in the testis interstitium were α-smooth muscle
actin (αSMA)(-), a peritubular myoid cells marker, suggesting that they are SLCs and PLCs. Besides, p57KIP2 was also expressed
in HSD3β(+) fetal Leydig cells. From PND1 to 14, BrdU(+)/αSMA(-), Ki67(+)/p57KIP2(+), and BrdU(+)/p57KIP2(+)
spindle-shaped cells were gradually decreased. From PND1 to 14, p57KIP in the αSMA(-)/p57KIP2(+) cells was peaked at
PND7 and decreased thereafter. In THY1(+) isolated SLCs, p57kip2 siRNA significantly increased ki67 and pcna mRNA and
pdgfrα mRNA, a differentiation marker and decreased nestin mRNA, a SLC marker. No significant difference in apoptosis
related genes mRNA was found after p57kip2 siRNA treatment. In HSD3β(+) PLCs, p57kip2 siRNA increased proapoptotic genes
mRNA, annexin V(+) early-apoptotic cells. Importantly, p57kip2 siRNA significantly decreased hsd3β6 and cyp17a1 mRNA
and progesterone production.
Conclusions: p57KIP2 may suppress proliferation and support stemness of SLCs. In PLCs, p57KIP2 may suppress apoptosis
and potentiate the steroidogenic differentiation. |
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| ISSN: | 2287-4208 2287-4690 |