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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Korean Society for Sexual Medicine and Andrology
2025-01-01
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| Series: | The World Journal of Men's Health |
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| author | Seung Hyun Park Kyung Noh Yoon Yang Xu Myung Chan Gye |
| author_facet | Seung Hyun Park Kyung Noh Yoon Yang Xu Myung Chan Gye |
| author_sort | Seung Hyun Park |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-42621e1527184901bbb1a9e1801a2ca8 |
| institution | Kabale University |
| issn | 2287-4208 2287-4690 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Korean Society for Sexual Medicine and Andrology |
| record_format | Article |
| series | The World Journal of Men's Health |
| spelling | doaj-art-42621e1527184901bbb1a9e1801a2ca82025-01-03T04:41:27ZengKorean Society for Sexual Medicine and AndrologyThe World Journal of Men's Health2287-42082287-46902025-01-0143117418710.5534/wjmh.230299Role of p57KIP2 in Stem and Progenitor Leydig Cells of Mouse TestesSeung Hyun Park0https://orcid.org/0000-0002-6230-8321Kyung Noh Yoon1https://orcid.org/0009-0001-2057-5907Yang Xu2https://orcid.org/0000-0003-3727-4091Myung Chan Gye3https://orcid.org/0000-0001-5682-3709Department of Life Science and Institute for Natural Sciences, Hanyang University, Seoul, KoreaDepartment of Life Science and Institute for Natural Sciences, Hanyang University, Seoul, KoreaDepartment of Life Science and Institute for Natural Sciences, Hanyang University, Seoul, KoreaDepartment of Life Science and Institute for Natural Sciences, Hanyang University, Seoul, KoreaPurpose: 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.cyclin-dependent kinase inhibitor p57leydig cellsmicestem cellstestes |
| spellingShingle | Seung Hyun Park Kyung Noh Yoon Yang Xu Myung Chan Gye Role of p57KIP2 in Stem and Progenitor Leydig Cells of Mouse Testes The World Journal of Men's Health cyclin-dependent kinase inhibitor p57 leydig cells mice stem cells testes |
| title | Role of p57KIP2 in Stem and Progenitor Leydig Cells of Mouse Testes |
| title_full | Role of p57KIP2 in Stem and Progenitor Leydig Cells of Mouse Testes |
| title_fullStr | Role of p57KIP2 in Stem and Progenitor Leydig Cells of Mouse Testes |
| title_full_unstemmed | Role of p57KIP2 in Stem and Progenitor Leydig Cells of Mouse Testes |
| title_short | Role of p57KIP2 in Stem and Progenitor Leydig Cells of Mouse Testes |
| title_sort | role of p57kip2 in stem and progenitor leydig cells of mouse testes |
| topic | cyclin-dependent kinase inhibitor p57 leydig cells mice stem cells testes |
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