Endoplasmic reticulum stress mediating downregulated StAR and 3-beta-HSD and low plasma testosterone caused by hypoxia is attenuated by CPU86017-RS and nifedipine

Liu, Guilai; Feng, Yu; Dai, De‐Zai; Zhang, Guolin; Zhang, Can; Yin, Dong

doi:10.1186/1423-0127-19-4

Cited by 32 publications

(31 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Degenerative changes in germ cells in aging rat showed oxidative stress and ER stress signaling pathway play important role [47,48]. Two independent study provide evidence that hypoxia downregulate androgen biosynthesizing genes such as steroidogenic acute regulatory protein (StAR) and 3-β-hydroxysteroid dehydrogenase (3β-HSD) in testis of rat by increasing calcium influx, oxidative stress and upregulation of ER stress signaling molecule Grp78, PERK and CHOP [49,50].…”

Section: Involvement Of Endoplasmic Reticulum Stress In Testis and Gementioning

confidence: 99%

The Role of Endoplasmic Reticulum Stress Response in Male Reproductive Physiology and Pathology: A Review

Karna

Shin

Choi

et al. 2020

World J Mens Health

View full text Add to dashboard Cite

Endoplasmic reticulum (ER) stress, defined as prolonged disturbances in protein folding and accumulation of unfolded proteins in the ER. Perturbation of the ER, such as distribution of oxidative stress, iron imbalance, Ca 2+ leakage, protein overload, and hypoxia, can cause ER stress. The cell reacts to ER stress by activating protective pathways, called the unfolded protein response (UPR), which is comprised of cellular mechanisms aimed for maintaining cellular homeostasis or, in case of excessively severe stress, at the initiation of cellular apoptosis. The three UPR signaling pathways from the ER stress sensors are initiated by activating transcription factor 6, inositol requiring enzyme 1, and protein kinase RNA-activated-like ER kinase. A number of physiological and pathological conditions, environmental toxicants and variety of pharmacological agents showed disruption of proper ER functions and thereby cause ER stress in male reproductive organ in rat model. The present review summarizes the existing data concerning the molecular and biological mechanism of ER stress in male reproduction and male infertility. ER stress initiated cell death pathway has been related to several diseases, including hypoxia, heath disease, diabetes, and Parkinson's disease. Although there is not enough evidence to prove the relationship between ER stress and male infertility in human, most studies in this review found that ER stress was correlated with male reproduction and infertility in animal models. The ER stress could be novel signaling pathway of regulating male reproductive cellular apoptosis. Infertility might be a result of disturbing the ER stress response during the process of male reproduction. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

show abstract

Section: Involvement Of Endoplasmic Reticulum Stress In Testis and Gementioning

confidence: 99%

The Role of Endoplasmic Reticulum Stress Response in Male Reproductive Physiology and Pathology: A Review

Karna

Shin

Choi

et al. 2020

World J Mens Health

View full text Add to dashboard Cite

show abstract

“…Madrid et al in 2013 reported that high-altitude hypoxia induced plasmatic and testicular testosterone decreased from the 5th day [5]. Liu et al reported in 2012 that in hypoxic rats, serum testosterone levels decreased and mRNA and protein expressions of testosterone biosynthesis related genes downregulated [23]. In this study, we determined the hypoxia effects on testosterone in Balb/c mouse serum and primary Leydig cells.…”

Section: Discussionmentioning

confidence: 97%

“…Liu et al reported in 2012 that in hypoxic rats, expression StAR and 3β-HSD were downregulated [23]. Su et al reported that increases in plasma leptin inhibited the expression of StAR and steroidogenic enzymes and attenuate adrenal responsiveness in hypoxic fetuses [30].…”

Section: Discussionmentioning

confidence: 99%

Hypoxia reduces testosterone synthesis in mouse Leydig cells by inhibiting NRF1-activated StAR expression

et al. 2017

View full text Add to dashboard Cite

Male fertility disorders play a key role in half of all infertility cases. Reduction in testosterone induced by hypoxia might cause diseases in reproductive system and other organs. Hypoxic exposure caused a significant decrease of NRF1. Software analysis reported that the promoter region of steroidogenic acute regulatory protein (StAR) contained NRF1 binding sites, indicating NRF1 promoted testicular steroidogenesis. The purpose of this study is to determine NRF1 is involved in testosterone synthesis; and under hypoxia, the decrease of testosterone synthesis is caused by lower expression of NRF1. We designed both in vivo and in vitro experiments. Under hypoxia, the expressions of NRF1 in Leydig cells and testosterone level were significantly decreased both in vivo and in vitro. Overexpression and interference NRF1 could induced StAR and testosterone increased and decreased respectively. ChIP results confirmed the binding of NRF1 to StAR promoter region. In conclusion, decline of NRF1 expression downregulated the level of StAR, which ultimately resulted in a reduction in testosterone synthesis.

show abstract

“…In humans and models of animal have found that hypoxic environment induces alterations of the male fertility, including low sperm counts, sperm mobility, plasma testosterone, and changes in testosterone levels (Farias et al, 2008;Pelliccione et al, 2011;Liu et al, 2012;Verratti and Giulio, 2012). An interesting thing to note is that spermatocyte apoptosis is the key in hypoxia-induced spermatogenic failure (Reyes et al, 2012b).…”

Section: Discussionmentioning

confidence: 99%

Hypoxia induces apoptosis of mouse spermatocyte GC‐2 cells through activation of autophagy

Zhou

Qian

Tong

et al. 2018

Cell Biology International

View full text Add to dashboard Cite

The aim of this study was to investigate the underlying mechanisms of hypoxia-induced apoptosis of GC-2spd (GC-2) cells. The GC-2 cells were treated with or without hypoxia for 12, 24, 48, and 72 h. Apoptosis of GC-2 cells was detected using TUNEL and flow cytometry. Fluorescence microscopic was used to observe the autophagy of GC-2 cells. Hypoxia-inducible factor-1alpha (HIF-1α), apoptosis-related protein and marker protein of autophagy levels were measured by Western blotting. Hypoxia induced apoptosis and autophagy of GC-2 cells, and increased expression of HIF-1α, LC3-II, Beclin-1, and pro-apoptotic protein, but reduced p62 and anti-apoptotic protein level. Meanwhile, hypoxia-induced HIF-1α mediated expression of apoptosis and autophagy-related protein in GC-2 cell. Furthermore, autophagy regulated hypoxia-induced apoptosis of GC-2 cell. Our data suggest that hypoxia induces apoptosis of GC-2 cell by activation of autophagy involving activation of the apoptosis signaling pathway under the hypoxic condition.

show abstract

Endoplasmic reticulum stress mediating downregulated StAR and 3-beta-HSD and low plasma testosterone caused by hypoxia is attenuated by CPU86017-RS and nifedipine

Cited by 32 publications

References 36 publications

The Role of Endoplasmic Reticulum Stress Response in Male Reproductive Physiology and Pathology: A Review

The Role of Endoplasmic Reticulum Stress Response in Male Reproductive Physiology and Pathology: A Review

Hypoxia reduces testosterone synthesis in mouse Leydig cells by inhibiting NRF1-activated StAR expression

Hypoxia induces apoptosis of mouse spermatocyte GC‐2 cells through activation of autophagy

Contact Info

Product

Resources

About