Effects of the IGF-1/PTEN/Akt/FoxO signaling pathway on male reproduction in rats subjected to water immersion and restraint stress

Abstract

The aim of the present study was to determine the effects of the insulin-like growth factor 1 (IGF-1)/phosphatase and tensin homologue deleted on chromosome 10 (PTEN)/Akt/forkhead box (FoxO) signaling pathway on male reproduction in rats subjected to water immersion and restraint stress (WRS). Sperm morphology, sperm malformation rate, and serum testosterone concentration were analyzed following WRS. In addition, the expression levels and immunolocalization of IGF-1, PTEN, Akt and FoxO proteins, as well as the rate of cell apoptosis in rat testes, were investigated. The results indicated that sperm malformation rate, serum testosterone concentration, and the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells were increased in the testes after WRS. Furthermore, IGF-1 and FoxO1 proteins were predominantly localized in the sperm cytoplasm during the late stages of spermatogenesis. FoxO1 protein was also localized in Leydig cell cytoplasm. PTEN and total Akt proteins were predominantly expressed in the cytoplasm of Leydig cells and spermatogonia. PTEN protein was also detected in vascular endothelial cells. In addition, IGF-1, PTEN, Akt1, Akt2, FoxO3 and FoxO4 gene expression levels were upregulated following WRS, and peaked after 7 h of WRS. During the recovery period, the expression levels of these genes gradually returned to normal levels. The present study demonstrated that WRS induced sperm damage in the testes. In addition, the results indicated that the IGF-1/PTEN/Akt/FoxO signaling pathway may serve an anti-stress role in the testes of rats subjected to WRS.

Nanopore-based full-length transcriptome sequencing of Muscovy duck (Cairina moschata) ovary

“…Among them, SGK1 activated by mTORC2 phosphorylates FOXO3a at Ser314, and then FOXO3a inhibits the expression of CDK1 and ultimately promotes cell proliferation ( Mori et al, 2014 ). FOXO3a is one of the most important target genes in the downstream of IGF-1/PTEN/Akt signaling pathway ( Huang et al, 2016 ). FOXO3a can regulate various cellular processes, such as cell cycle, apoptosis, DNA damage repair ( Liu et al, 2015 ).…”

Expression Regulation and Physiological Role of Transcription Factor FOXO3a During Ovarian Follicular Development

“…In mammals, the primordial follicle is the basic female reproductive unit and the only form of ovarian cell reserve ( Wei et al, 2012 , 2019 ; Huang et al, 2016 ; Wu et al, 2019 ). Primitive follicular pools are formed during early life such as the late embryonic stage in humans and the fourth day after birth in rats ( Tang et al, 2017 ).…”

“…Follicular development is a complex reproduction-related physiological process characterized by cell proliferation, differentiation, and apoptosis. Typically, based on morphology and function, follicular development can be artificially divided into different stages, including primordial follicles, primary follicles, secondary follicles, and mature follicles ( Wei et al, 2012 , 2019 ; Huang et al, 2016 ; Wu et al, 2019 ). Notably, various diseases could be induced by follicular dysplasia, including premature ovarian failure, polycystic follicular syndrome, and infertility ( Yang et al, 2010 ; Thanatsis et al, 2019 ).…”

Investigation of the underling mechanism of ketamine for antidepressant effects in treatment‑refractory affective disorders via molecular profile analysis

“…Hence, FoxO3a-deficient mice presented with an antidepressant-like behavior (39). The FoxO signaling pathway is considered to be a therapeutic target in cancer (40), and mediates stress responses (41,42). Therefore, it is hypothesized that the mTOR and FoxO signaling pathways may be involved in the underlying mechanism of antidepressant effects of ketamine.…”