scholarly journals Deletion of Eqtn in mice reduces male fertility and sperm–egg adhesion

Reproduction ◽  
2018 ◽  
Vol 156 (6) ◽  
pp. 579-590 ◽  
Author(s):  
Chizuru Ito ◽  
Kenji Yamatoya ◽  
Keiichi Yoshida ◽  
Lisa Fujimura ◽  
Hajime Sugiyama ◽  
...  
Keyword(s):  
Mouse Model ◽  
Zona Pellucida ◽  
Male Fertility ◽  
Acrosome Reaction ◽  
Underlying Mechanism ◽  
Mouse Mutant ◽  
Sperm Proteins

A number of sperm proteins are involved in the processes from gamete adhesion to fusion, but the underlying mechanism is still unclear. Here, we established a mouse mutant, the EQUATORIN-knockout (EQTN-KO, Eqtn − / − ) mouse model and found that the EQTN-KO males have reduced fertility and sperm–egg adhesion, while the EQTN-KO females are fertile. Eqtn − / − sperm were normal in morphology and motility. Eqtn − / − -Tg (Acr-Egfp) sperm, which were produced as the acrosome reporter by crossing Eqtn − / − with Eqtn +/+ -Tg(Acr-Egfp) mice, traveled to the oviduct ampulla and penetrated the egg zona pellucida of WT females. However, Eqtn − / − males mated with WT females showed significant reduction in both fertility and the number of sperm attached to the zona-free oocyte. Sperm IZUMO1 and egg CD9 behaved normally in Eqtn − / − sperm when they were fertilized with WT egg. Another acrosomal protein, SPESP1, behaved aberrantly in Eqtn − / − sperm during the acrosome reaction. The fertility impairment of EQTN/SPESP1-double KO males lacking Eqtn and Spesp1 (Eqtn/Spesp1 − / − ) was more severe compared with that of Eqtn − / − males. Eqtn − / − -Tg (Eqtn) males, which were generated to rescue Eqtn − / − males, restored the reduced fertility.

scholarly journals Human Zona Pellucida Glycoproteins: Binding Characteristics With Human Spermatozoa and Induction of Acrosome Reaction

2021 ◽  
Vol 9 ◽  
Author(s):  
Satish Kumar Gupta
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Protein Interactions ◽  
Zona Pellucida ◽  
Acrosome Reaction ◽  
Human Sperm ◽  
Transgenic Mouse Model ◽  
Human Spermatozoa ◽  
Binding Characteristics ◽  
Mouse Lines

Human zona pellucida (ZP) matrix is composed of four glycoproteins designated as ZP glycoprotein -1 (ZP1), -2 (ZP2), -3 (ZP3), and -4 (ZP4). Mutations in the genes encoding human ZP glycoproteins are one of the causative factors leading to abnormal ZP matrix and infertility in women. Relevance of the human ZP glycoproteins in ‘sperm–oocyte’ binding has been delineated by using either transgenic animal models expressing human zona proteins or purified native/recombinant human zona proteins. Studies based on the purified native/recombinant human zona proteins revealed that ZP1, ZP3, and ZP4 primarily bind to the capacitated acrosome-intact human spermatozoa whereas ZP2 binds to acrosome-reacted spermatozoa. On the contrary, human spermatozoa binds to the eggs obtained from transgenic mouse lines expressing human ZP2 but not to those expressing human ZP1, ZP3, and ZP4 suggesting that ZP2 has an important role in human ‘sperm–oocyte’ binding. Further studies using transgenic mouse lines showed that the N-terminus of human ZP2 mediate the taxon-specific human sperm–oocyte binding. Both glycans and protein-protein interactions have a role in human gamete interaction. Further studies have revealed that the purified native/recombinant human ZP1, ZP3, and ZP4 are competent to induce acrosome reaction. Human sperm binds to the mouse transgenic eggs expressing human ZP1-4 instead of mouse ZP1-3 proteins, penetrated the ZP matrix and accumulated in the perivitelline space, which were acrosome-reacted suggesting that human ZP2 in transgenic mouse model also induce acrosome reaction. In humansN-linked glycosylation of zona proteins have been shown to play an important role in induction of the acrosome reaction. Hence in humans, based on studies using transgenic mouse model as well as purified native/recombinant zona proteins, it is likely that more than one zona protein is involved in the ‘sperm–oocyte’ binding and induction of the acrosome reaction.

scholarly journals Hop Bitter Acids Increase Hippocampal Dopaminergic Activity in a Mouse Model of Social Defeat Stress

2020 ◽  
Vol 21 (24) ◽  
pp. 9612
Author(s):  
Yasuhisa Ano ◽  
Shiho Kitaoka ◽  
Rena Ohya ◽  
Keiji Kondo ◽  
Tomoyuki Furuyashiki
Keyword(s):  
Mouse Model ◽  
Chronic Administration ◽  
Social Defeat ◽  
Underlying Mechanism ◽  
Mental Illnesses ◽  
Social Avoidance ◽  
Social Defeat Stress ◽  
Dopaminergic Activity ◽  
Healthy Older Adults ◽  
Bitter Acids

As daily lifestyle is closely associated with mental illnesses, diet-based preventive approaches are receiving attention. Supplementation with hop bitter acids such as iso-α-acids (IAA) and mature hop bitter acids (MHBA) improves mood states in healthy older adults. However, the underlying mechanism remains unknown. Since acute oral consumption with IAA increases dopamine levels in hippocampus and improves memory impairment via vagal nerve activation, here we investigated the effects of chronic administration of hop bitter acids on the dopaminergic activity associated with emotional disturbance in a mouse model of repeated social defeat stress (R-SDS). Chronic administration of IAA and MHBA significantly increased dopaminergic activity based on the dopamine metabolite to dopamine ratio in the hippocampus and medial prefrontal cortex following R-SDS. Hippocampal dopaminergic activity was inversely correlated with the level of R-SDS-induced social avoidance with or without IAA administration. Therefore, chronic treatment with hop bitter acids enhances stress resilience-related hippocampal dopaminergic activity.

scholarly journals Altered Expression of Peroxiredoxins in Mouse Model of Progressive Myoclonus Epilepsy upon LPS-Induced Neuroinflammation

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 357
Author(s):  
Mojca Trstenjak Prebanda ◽  
Petra Matjan-Štefin ◽  
Boris Turk ◽  
Nataša Kopitar-Jerala
Keyword(s):  
Mouse Model ◽  
Redox Homeostasis ◽  
Underlying Mechanism ◽  
Loss Of Function ◽  
Altered Expression ◽  
Lps Challenge ◽  
Progressive Myoclonus Epilepsy ◽  
Myoclonus Epilepsy ◽  
The Brain ◽  
Deficient Mice

Stefin B (cystatin B) is an inhibitor of endo-lysosomal cysteine cathepsin, and the loss-of-function mutations in the stefin B gene were reported in patients with Unverricht–Lundborg disease (EPM1), a form of progressive myoclonus epilepsy. Stefin B-deficient mice, a mouse model of the disease, display key features of EPM1, including myoclonic seizures. Although the underlying mechanism is not yet completely clear, it was reported that the impaired redox homeostasis and inflammation in the brain contribute to the progression of the disease. In the present study, we investigated if lipopolysaccharide (LPS)-triggered neuroinflammation affected the protein levels of redox-sensitive proteins: thioredoxin (Trx1), thioredoxin reductase (TrxR), peroxiredoxins (Prxs) in brain and cerebella of stefin B-deficient mice. LPS challenge was found to result in a marked elevation of Trx1 and TrxR in the brain and cerebella of stefin B deficient mice, while Prx1 was upregulated only in cerebella after LPS challenge. Mitochondrial peroxiredoxin 3 (Prx3), was upregulated also in the cerebellar tissue lysates prepared from unchallenged stefin B deficient mice, while after LPS challenge Prx3 was upregulated in stefin B deficient brain and cerebella. Our results imply the role of oxidative stress in the progression of the disease.

scholarly journals Inhibition of Kirsten-Ras reduces fibrosis and protects against renal dysfunction in a mouse model of chronic folic acid nephropathy

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Lucy J. Newbury ◽  
Jui-Hui Wang ◽  
Gene Hung ◽  
Bruce M. Hendry ◽  
Claire C. Sharpe
Keyword(s):  
Folic Acid ◽  
Kidney Disease ◽  
Mouse Model ◽  
Renal Dysfunction ◽  
Antisense Oligonucleotides ◽  
Underlying Mechanism ◽  
Therapeutic Benefit ◽  
End Stage

Abstract Chronic Kidney Disease is a growing problem across the world and can lead to end-stage kidney disease and cardiovascular disease. Fibrosis is the underlying mechanism that leads to organ dysfunction, but as yet we have no therapeutics that can influence this process. Ras monomeric GTPases are master regulators that direct many of the cytokines known to drive fibrosis to downstream effector cascades. We have previously shown that K-Ras is a key isoform that drives fibrosis in the kidney. Here we demonstrate that K-Ras expression and activation are increased in rodent models of CKD. By knocking down expression of K-Ras using antisense oligonucleotides in a mouse model of chronic folic acid nephropathy we can reduce fibrosis by 50% and prevent the loss of renal function over 3 months. In addition, we have demonstrated in vitro and in vivo that reduction of K-Ras expression is associated with a reduction in Jag1 expression; we hypothesise this is the mechanism by which targeting K-Ras has therapeutic benefit. In conclusion, targeting K-Ras expression with antisense oligonucleotides in a mouse model of CKD prevents fibrosis and protects against renal dysfunction.

Complete removal of the zona pellucida and pregnancy outcome in a mouse model

2011 ◽  
Vol 96 (3) ◽  
pp. S85
Author(s):  
A.Y. Armstrong ◽  
E. Wawrousek ◽  
Y.-L. Feng
Keyword(s):  
Mouse Model ◽  
Pregnancy Outcome ◽  
Zona Pellucida ◽  
Complete Removal

Simvastatin Prevents Neurodegeneration in the MPTP Mouse Model of Parkinson’s Disease via Inhibition of A1 Reactive Astrocytes

2021 ◽  
pp. 1-8
Author(s):  
Ren-Wei Du ◽  
Wen-Guang Bu
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Underlying Mechanism ◽  
Reactive Astrocytes ◽  
Dopamine Neurons ◽  
Neuron Death ◽  
Neurologic Disorders

Emerging evidence indicates that A1 reactive astrocytes play crucial roles in the pathogenesis of Parkinson’s disease (PD). Thus, development of agents that could inhibit the formation of A1 reactive astrocytes could be used to treat PD. Simvastatin has been touted as a potential neuroprotective agent for neurologic disorders such as PD, but the specific underlying mechanism remains unclear. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD and primary astrocytes/neurons were prepared to investigate the effects of simvastatin on PD and its underlying mechanisms in vitro and in vivo. We show that simvastatin protects against the loss of dopamine neurons and behavioral deficits in the MPTP mouse model of PD. We also found that simvastatin suppressed the expression of A1 astrocytic specific markers in vivo and in vitro. In addition, simvastatin alleviated neuron death induced by A1 astrocytes. Our findings reveal that simvastatin is neuroprotective via the prevention of conversion of astrocytes to an A1 neurotoxic phenotype. In light of simvastatin favorable properties, it should be evaluated in the treatment of PD and related neurologic disorders characterized by A1 reactive astrocytes.

Native zona pellucida structure is required for completion of sperm acrosome reaction in porcine fertilization

1994 ◽  
Vol 41 (6) ◽  
pp. 1307-1313 ◽  
Author(s):  
M. Yoshizawa ◽  
T. Nagai ◽  
N. Yonezawa ◽  
M. Nakano
Keyword(s):  
Zona Pellucida ◽  
Acrosome Reaction ◽  
Sperm Acrosome Reaction ◽  
Sperm Acrosome

scholarly journals Metabolic Syndrome and Reproduction

2021 ◽  
Vol 22 (4) ◽  
pp. 1988
Author(s):  
Francesco Lotti ◽  
Sara Marchiani ◽  
Giovanni Corona ◽  
Mario Maggi
Keyword(s):  
Metabolic Syndrome ◽  
Male Fertility ◽  
English Language ◽  
Negative Impact ◽  
Reproductive Potential ◽  
Underlying Mechanism ◽  
Semen Parameters ◽  
Preclinical Studies ◽  
Medline Search ◽  
High Prevalence

Metabolic syndrome (MetS) and infertility are two afflictions with a high prevalence in the general population. MetS is a global health problem increasing worldwide, while infertility affects up to 12% of men. Despite the high prevalence of these conditions, the possible impact of MetS on male fertility has been investigated by a few authors only in the last decade. In addition, underlying mechanism(s) connecting the two conditions have been investigated in few preclinical studies. The aim of this review is to summarize and critically discuss available clinical and preclinical studies on the role of MetS (and its treatment) in male fertility. An extensive Medline search was performed identifying studies in the English language. While several studies support an association between MetS and hypogonadism, contrasting results have been reported on the relationship between MetS and semen parameters/male infertility, and the available studies considered heterogeneous MetS definitions and populations. So far, only two meta-analyses in clinical and preclinical studies, respectively, evaluated this topic, reporting a negative association between MetS and sperm parameters, testosterone and FSH levels, advocating, however, larger prospective investigations. In conclusion, a possible negative impact of MetS on male reproductive potential was reported; however, larger studies are needed.

Sign in / Sign up

Export Citation Format

Share Document