Abstract
The rapid and efficient clearance of apoptotic germ cells (GCs) by Sertoli cells (SCs) is important for spermatogenesis. High mitochondrial activity in phagocytes is critical for continued clearance of apoptotic cells. However, the underlying molecular mechanism is poorly understood. Glycogen synthase kinase-3α (GSK3α) is a protein kinase that participates in the regulation of mitochondrial activity. Immunohistochemistry evidenced the predominant presence of the Ser21 phosphorylation GSK3α (inactivation) signal in SCs. Heat shock-induced apoptosis of GCs and dephosphorylation of GSK3α in SCs is a perfect model to investigate the role of GSK3α in phagocytic action. The number of apoptotic GCs was significantly lower in GSK3α inhibitor pre-treated mice with HS compared to normal control. In vitro phagocytosis assays shown that the phagocytic activity in GSK3α activated SCs was downregulated, while GSK3α inhibitor supplementation restored this process. Moreover, GSK3α activation participates in the alteration of the mitochondrial ultrastructure and activity. In particular, GSK3α activation inhibits mitochondrial fission via phosphorylation of dynamin related protein 1 at Ser637. Changes of mitochondrial activity resulted in the accumulation of lipid droplets and the alteration of metabolism pattern in SCs. In summary, our results demonstrate that inactivation of GSK3α is required for mitochondria-mediated apoptotic GCs phagocytosis in SCs.
Highlights
During mammalian spermatogenesis, more than 75% of the developing spermatogenic cells undergo apoptosis before maturation [1]
Ser9 p-GSK3β can be found via cytoplasmic immunostaining in www.aging-us.com spermatogonia and preleptotene spermatocytes (Fig. 1A)
The obtained results suggest a novel role of Glycogen synthase kinase-3α (GSK3α) in the regulation of mitochondria-mediated apoptotic germ cells (GCs) phagocytosis in Sertoli cells (SCs)
Summary
More than 75% of the developing spermatogenic cells undergo apoptosis before maturation [1]. Apoptotic spermatogenic cells can provide energy sources for Sertoli cells (SCs) [2]. The rapid and efficient degradation of apoptotic germ cells (GCs) by SCs has been suggested as crucial for appropriate germ cell development and differentiation. The occurrence of apoptosis at various stages of spermatogenesis has been observed frequently, few apoptotic GCs are histochemical detectable in normal www.aging-us.com adult testis. This is most probably due to their rapid elimination via phagocytosis. The investigation of these phenomena has recently become more intensive, most mechanisms still remain unclear
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