Abstract
Selective regulation of gene transcription is clearly important for cells to orchestrate an adaptive response to heat stress. We previously showed that Metastasis Associated Protein 1 (MTA1), a component of the nucleosome remodeling and deacetylase (NuRD) complex, operates as a negative coregulator of p53 in the maintenance of the apoptotic balance in pachytene spermatocytes (PS) after heat stress, although specific mechanisms are not well defined. The purpose of the current study was to investigate potential upstream signaling events activating MTA1 pathway in murine PS. Using murine sialoadenectomy model, it was demonstrated that deprivation of circulated EGF significantly impaired the in vivo expression of MTA1 in the PS. The upstream regulation of MTA1 expression during meiosis by endogenous EGF was further confirmed in vitro using a selective Epidermal Growth Factor Receptor (EGFR) inhibitor, tryphostin AG1478. Moreover, inhibition of EGF signaling by AG1478 treatment significantly suppressed the heat stress-induced MTA1 in PS. The available data collectively suggest that EGF signaling regulates the expression of MTA1 in PS, and early activation of EGF/MTA1 cascade in PS in response to heat stress may serve as an intrinsic self-defensive mechanism maintaining apoptotic balance during meiotic heat stress.
Highlights
Normal testicular function occurs in a low-temperature environment
We firstly studied the evolution of the plasma and intratesticular Epidermal Growth Factor (EGF) levels after sialoadenectomy
The testicular EGF concentration began to decrease at the 3rd d and started to restore 14th d after sialoadenectomy, with the minimal level observed at the 7th d after surgery (Figure 1B)
Summary
Normal testicular function occurs in a low-temperature environment. the temperature of scrotum can be affected by numerous external factors such as posture, clothing, lifestyle, occupation and season [1]. During the complicated process of spermatogenesis, the DNA of the spermatocytes in meiosis is most vulnerable to the introduction of a range of errors upon hyperthermal stimulations In this regard, multifactorial protective mechanisms are warranted in spermatocytes to ensure the maintenance of cellular integrity during stress condition [2]. MTA1 expression is gradually increased in tetraploid primary spermatocytes since 14 days postnatal During this course, where continuous meiosis takes place, messenger RNA storage is a common phenomenon seen In Pachytene Spermatocytes (PS), where the messengers are saved for utilization during spermatogenesis. In this regard, the accumulation of MTA1 may imply its role in testicular development [4]. Because MTA1 is localized in the nuclear site, the molecular events by which the rise in extracellular temperature is transduced into intracellular responses of MTA1 remain to be defined
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