YES1 Activation Elicited by Heat Stress Is Anti-Apoptotic in Mouse Pachytene Spermatocytes1

Abstract

Deregulated expression of protein tyrosine phosphorylation has been implicated in testicular response to different stimuli. Herein, YES1, a nonreceptor protein tyrosine kinase, was found to be significantly up-regulated in pachytene spermatocytes (PS) during early recovery from a transient testicular heat stress. Coculture of PS with Sertoli cells (SCs) could enhance the hyperthermia-induced YES1 activation, indicative of a positive regulation of the paracrine signaling. Moreover, SU6656, a selective YES1 inhibitor, was shown to effectively block YES1 activity, thereafter resulting in a dramatic increase of heat stress-induced apoptosis in primary cultured PS. Mechanistically, the antiapoptotic effect of YES1 activation in response to testicular heat insult may mediate via the regulation of extracellular signal-regulated kinase (ERK)/metastasis-associated 1 (MTA1) cascade. From a clinical standpoint, a notably higher level of YES1 expression was observed in the pathological testis from varicocele patients as compared to a negligible staining in the control group. Taken together, our present results provide the first evidence that the YES1/ERK/MTA1/p53 cascade may serve as a naturally occurring, indispensable self-defensive mechanism maintaining apoptotic balance during meiotic heat stress. Our study may have also partially answered the question of how activation of signal pathways at the cell membrane surface interacts with the key regulatory events occurring in the nucleus during testicular heat shock.

Bax and Bcl‐2 are involved in the apoptosis induced by local testicular heating in the boar testis

“…Our results showed that the local testicular heating caused a significant increase in the TUNEL‐positive cell numbers of round and elongated spermatids. Our results agree with prior reports (Lue et al., ; Yamamoto et al., ; Oldereid et al., ; Hikim et al., ; Zhang et al., , ; Merico et al., ; Jia et al., ; Paul et al., ; Kanter et al., ; Liang et al., ; Henning et al., ), in which heat stress resulted in the apoptosis of germ cells. But a little different from the report by Lue et al.…”

“…In this study, a self‐made thermo‐controlled 42°C blanket was used in the local testicular heating group. Recently, several studies in a few animals suggested that testes exposed to above body temperature (40–43°C) cause apoptosis in germ cells, including mice (Merico et al., ; Paul, Teng, & Saunders, ; Liang, Dong, Zhao, & Li, ), rats (Yamamoto et al., ; Hikim et al., ; Jia et al., ), dogs (Henning et al., ) and monkeys (Zhang et al., , ). Several studies also confirmed that exposing testes to above body temperature affects normal spermatogenesis, sperm fertility and male fertility (Gnay et al., ; Ikeda et al., ; Gau et al., ; Li et al., ; Guo et al., ; Salces‐Ortiz et al., ; Xun et al., ).…”

Upregulation and nuclear translocation of testicular ghrelin protects differentiating spermatogonia from ionizing radiation injury

“…44 Briefly, sections were deparaffinaged, rehydrated to distilled water, and immersed in boiling citrate buffer for 10 min to retrieve antigen. After endogenous peroxidase activity had been blocked with 0.3% H 2 O 2 in methanol for 30 min, slides were incubated with the primary antibody diluted in PBS, at 4 °C overnight in a moist box.…”

Hyperglycemia-induced PATZ1 negatively modulates endothelial vasculogenesis via repression of FABP4 signaling

“…The immunohistochemical staning was conducted as previously described [11,12]. Slides were incubated at 4°C overnight in a moist box with the rabbit anti-PATZ1 antibody (Santa Cruz Biotechnology, Shanghai, China) at a dilution of 1:100.…”

“…For example, Patz1 is highly expressed in the pluripotent mouse inner cell mass compared with the nonpluripotent trophectoderm. Moreover, the Patz1 genomic region is bound by various important transcription factors (TFs), such as Oct4, M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 11 Nanog, Sox2, Klf4, and c-Myc [5]. Considering that the capablility of differentiating to regenerate endothelial cell populations in ECFCs resembles the same important characteristic in stem cells, it will therefore be of great interest to test if endothelial PATZ1 modulates angiogenesis via regulating certain pluripotent pathways.…”