Induction of Excessive Endoplasmic Reticulum Stress in the Drosophila Male Accessory Gland Results in Infertility

Chow, Clement Y.; Avila, Frank W.; Clark, Andrew G.; Wolfner, Mariana F.

doi:10.1371/journal.pone.0119386

Cited by 38 publications

(41 citation statements)

References 47 publications

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“…ER stress chaperone Grp78 predominantly presents in pachytene spermatocytes, suggest ER stress signaling pathway have important role in the process of spermatogenesis [44]. A study in Drosophila male reports ER stress gene are highly express in male accessory gland and induced strong ER stress decrease fertility [7]. A study by Kim et al [13] reported that repetitive cycle of testicular hyperthermia leads to ER stress associated apoptosis of spermatocytes in mouse testis by activation of IRE1-JNK and PERK pathway.…”

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

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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.

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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

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“…Excessive endoplasmic reticulum stress induced by diabetes causes alterations in the homeostasis of the endoplasmic reticulum and subsequently reduces protein synthesis [59,60]. In addition, excessive endoplasmic reticulum stress is linked with male infertility [80]. Guzel et al [81] state that spermatogenesis requires intensive protein synthesis to continue the developmental process from spermatogonia to spermatozoa, however, uncontrolled endoplasmic reticulum stress inhibits spermatogenesis.…”

Section: Sperm Unique Protein Upon Fc Treatmentmentioning

confidence: 99%

Sperm Proteomics Analysis of Diabetic Induced Male Rats as Influenced by Ficus carica Leaf Extract

et al. 2020

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Diabetes mellitus is shown to bring negative effects on male reproductive health due to long-term effects of insulin deficiency or resistance and increased oxidative stress. Ficus carica (FC), an herbal plant, known to have high antioxidant activity and antidiabetic properties, has been used traditionally to treat diabetes. The objective of this study is to determine the potential of the FC leaf extract in improving sperm quality of streptozotocin (STZ) induced diabetic male rats from proteomics perspective. A total of 20 male rats were divided into four groups; normal (nondiabetic rats), negative control (diabetic rats without treatment), positive control (diabetic rats treated with 300 mg/kg metformin), and FC group (diabetic rats treated with 400 mg/kg FC extract). The treatments were given via oral gavage for 21 consecutive days. The fasting blood glucose (FBG) level of FC treated group demonstrated a significant (p < 0.05) decrease compared to negative group after 21 days of treatment, as well as a significant (p < 0.05) increase in the sperm quality parameters compared to negative group. Sperm proteomics analysis on FC treated group also exhibited the increase of total protein expression especially the proteins related to fertility compared to negative group. In conclusion, this study clearly justified that FC extract has good potential as antihyperglycemic and profertility agent that may be beneficial for male diabetic patients who have fertility problems.

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“…N PEB = 8, N Cont = 4. (Chow et al 2015) suggests that the accessory gland proteins identified are part of the AMP. SFPs with functions unrelated to the MP have been observed in the AMP: in experiments using sex-peptide::GFP fusions, GFP signal is detected throughout the AMP (but not the PMP) after MP coagulation has occurred [see Figure 3 in Minami et al (2012)].…”

Section: Identification Of Additional Mp Proteinsmentioning

confidence: 99%

“…Expressing Rh1 G69D in secretory tissues causes high levels of endoplasmic reticulum (ER) stress, which blocks translation by inducing the unfolded protein response (Ryoo et al 2007). Driving expression of Rh1 G69D in the male accessory gland-the major site of Drosophila SFP synthesis-blocks translation and secretion of SFPs from this tissue (Chow et al 2015). Expressing Rh1 G69D in the EB similarly blocks the function of this tissue.…”

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confidence: 99%

Retention of Ejaculate by Drosophila melanogaster Females Requires the Male-Derived Mating Plug Protein PEBme

et al. 2015

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Within the mated reproductive tracts of females of many taxa, seminal fluid proteins (SFPs) coagulate into a structure known as the mating plug (MP). MPs have diverse roles, including preventing female remating, altering female receptivity postmating, and being necessary for mated females to successfully store sperm. The Drosophila melanogaster MP, which is maintained in the mated female for several hours postmating, is comprised of a posterior MP (PMP) that forms quickly after mating begins and an anterior MP (AMP) that forms later. The PMP is composed of seminal proteins from the ejaculatory bulb (EB) of the male reproductive tract. To examine the role of the PMP protein PEBme in D. melanogaster reproduction, we identified an EB GAL4 driver and used it to target PEBme for RNA interference (RNAi) knockdown. PEBme knockdown in males compromised PMP coagulation in their mates and resulted in a significant reduction in female fertility, adversely affecting postmating uterine conformation, sperm storage, mating refractoriness, egg laying, and progeny generation. These defects resulted from the inability of females to retain the ejaculate in their reproductive tracts after mating. The uncoagulated MP impaired uncoupling by the knockdown male, and when he ultimately uncoupled, the ejaculate was often pulled out of the female. Thus, PEBme and MP coagulation are required for optimal fertility in D. melanogaster. Given the importance of the PMP for fertility, we identified additional MP proteins by mass spectrometry and found fertility functions for two of them. Our results highlight the importance of the MP and the proteins that comprise it in reproduction and suggest that in Drosophila the PMP is required to retain the ejaculate within the female reproductive tract, ensuring the storage of sperm by mated females.KEYWORDS mating plug; sperm storage; PEBme; Drosophila reproduction I N numerous species comprising diverse taxa, a solidified structure forms inside the female reproductive tract during (or shortly after) mating that is referred to as the mating plug (MP; also called the copulatory plug; we will refer to these structures collectively as MPs). MPs are largely a coagulation of male seminal fluid components. In species that produce a MP, its role in reproduction varies. In some species, MP formation is thought to guard against sperm competition. For example, in primates, MPs are seen most often in species whose females mate multiply (Dixson and Anderson 2002). Primate MPs have been suggested to prevent remating (Dorus et al. 2004), thus acting as a form of passive mate guarding (Dunham and Rudolf 2009). In the mouse, perturbing (Murer et al. 2001) or preventing (Dean 2013) MP formation reduces male fertility; in the absence of MP formation, sperm migration to the sites of fertilization is impaired (Dean 2013) receptivity in the short term (Polak et al. 1998;Bretman et al. 2010). In bumblebees, MPs physically switch off receptivity Sauter et al. 2001) and have functions related to sperm competition (Duvo...

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Induction of Excessive Endoplasmic Reticulum Stress in the Drosophila Male Accessory Gland Results in Infertility

Cited by 38 publications

References 47 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

Sperm Proteomics Analysis of Diabetic Induced Male Rats as Influenced by Ficus carica Leaf Extract

Retention of Ejaculate by Drosophila melanogaster Females Requires the Male-Derived Mating Plug Protein PEBme

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