Neonatal corticosterone administration increases p27-positive Sertoli cell number and decreases Sertoli cell number in the testes of mice at prepuberty

Abstract

Cortisol and corticosterone (CORT) are steroid, antistress hormones and one of the glucocorticoids in humans and animals, respectively. This study evaluated the effects of CORT administration on the male reproductive system in early life stages. CORT was subcutaneously injected at 0.36 (low-), 3.6 (middle-), and 36 (high-dosed) mg/kg body weight from postnatal day (PND) 1 to 10 in ICR mice. We observed a dose-dependent increase in serum CORT levels on PND 10, and serum testosterone levels were significantly increased only in high-dosed-CORT mice. Triiodothyronine levels were significantly higher in the low-dosed mice but lower in the middle- and high-dosed mice. However, testicular weights did not change significantly among the mice. Sertoli cell numbers were significantly reduced in low- and middle-dosed mice, whereas p27-positive Sertoli cell numbers increased in low- and middle-dosed mice. On PND 16, significant increases in testicular and relative testicular weights were observed in all-dosed-CORT mice. On PND 70, a significant decrease in testicular weight, Sertoli cell number, and spermatozoa count was observed. These results revealed that increased serum CORT levels in early life stages could induce p27 expression in Sertoli cells and terminate Sertoli cell proliferation, leading to decreased Sertoli cell number in mouse testes.

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“…However, GC can cause a decrease in lactate content in testes and TM4 cells and a downregulation of phagocytic activity in Sertoli cells, accompanied by a decrease in mitochondrial activity through the upregulation of PDK4 (Recombinant Pyruvate Dehydrogenase Kinase 4) [ 48 ]. In addition, elevated serum CORT (Cortisol) levels induce p27 (a cell cycle protein-dependent kinase inhibitor) expression in Sertoli cells and terminate Sertoli cell proliferation, leading to a decrease in the number of Sertoli cells in mouse testes [ 49 ]. From the above results, GC can affect the value addition of Sertoli cells and induce disturbance of lactate metabolism in Sertoli cells, affecting their phagocytic ability, causing testicular inflammation, and impairing reproductive function.…”