Male and Couple Fertility Impairment due to HPV-DNA Sperm Infection: Update on Molecular Mechanism and Clinical Impact—Systematic Review

Recent evidences identify Human Papillomavirus (HPV) sperm infection as a possible cause of male and couple infertility. It acts through different mechanisms at various steps of human conception and early gestational development. We performed a systematic review to assess the role of HPV semen infection on male and couple infertility. Analysis of available and eligible data does not permit us to fund clear evidences about clinical impact of HPV infection on fertility, although sperm parameters impairment is the most widely recognized effect. Regarding biomolecular implications, the available data are often conflicting. More studies are required to define the role of HPV sperm infection in clinical practice. The great majority of evidences are obtained byin vitrostudies and this fact represents a limitation for the clinical management of HPVDNA sperm infection. Understanding the biological significance of HPV-DNA semen infection could permit us to explain most of the idiopathic male and couple infertility, leading to a better management of infertile men and a better timing for sperm banking storage before ART cycles.

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A Review on Melatonin’s Effects in Cancer: Potential Mechanisms

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520617666171121120223 ◽

2018 ◽

Vol 18 (7) ◽

pp. 985-992 ◽

Cited By ~ 3

Author(s):

Aysegul Hanikoglu ◽

Ertan Kucuksayan ◽

Rana Cagla Akduman ◽

Tomris Ozben

Keyword(s):

Systematic Review ◽

Antioxidant Activity ◽

Membrane Receptors ◽

Cancer Development ◽

Secretory Product ◽

Prevention And Treatment ◽

G Protein Coupled

This systematic review aims to elucidate the role of melatonin (N-acetyl-5-metoxy-tryptamine) (MLT) in the prevention and treatment of cancer. MLT is a pineal gland secretory product, an evolutionarily highly conserved molecule; it is also an antioxidant and an impressive protector of mitochondrial bioenergetic activity. MLT is characterized by an ample range of activities, modulating the physiology and molecular biology of the cell. Its physiological functions relate principally to the interaction of G Protein-Coupled MT1 and MT2 trans-membrane receptors (GPCRs), a family of guanidine triphosphate binding proteins. MLT has been demonstrated to suppress the growth of various tumours both, in vivo and in vitro. In this review, we analyze in depth, the antioxidant activity of melatonin, aiming to illustrate the cancer treatment potential of the molecule, by limiting or reversing the changes occurring during cancer development and growth.

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The Role of Biomimetic Hypoxia on Cancer Cell Behaviour in 3D Models: A Systematic Review

Cancers ◽

10.3390/cancers13061334 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1334

Author(s):

Ye Liu ◽

Zahra Mohri ◽

Wissal Alsheikh ◽

Umber Cheema

Keyword(s):

Systematic Review ◽

Cellular Response ◽

3D Culture ◽

3D Models ◽

In Vitro Models ◽

Research Findings ◽

Tissue Models

The development of biomimetic, human tissue models is recognized as being an important step for transitioning in vitro research findings to the native in vivo response. Oftentimes, 2D models lack the necessary complexity to truly recapitulate cellular responses. The introduction of physiological features into 3D models informs us of how each component feature alters specific cellular response. We conducted a systematic review of research papers where the focus was the introduction of key biomimetic features into in vitro models of cancer, including 3D culture and hypoxia. We analysed outcomes from these and compiled our findings into distinct groupings to ascertain which biomimetic parameters correlated with specific responses. We found a number of biomimetic features which primed cancer cells to respond in a manner which matched in vivo response.

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Lack of HPV in pterygium with no evidence of autoinoculation and the role of cytokines in pterygium with dry eye

Scientific Reports ◽

10.1038/s41598-021-82114-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lita Uthaithammarat ◽

Ngamjit Kasetsuwan ◽

Yuda Chongpison ◽

Pimpetch Kasetsuwan ◽

Usanee Reinprayoon ◽

...

Keyword(s):

Dry Eye ◽

Hpv Infection ◽

Cross Sectional Study ◽

Urine Samples ◽

Vascular Endothelial ◽

Cross Sectional ◽

Hpv Dna ◽

Polymerase Chain ◽

Endothelial Growth Factor

AbstractThis study evaluated human papillomavirus’s (HPV) role in pterygium pathogenesis, its autoinoculation from genitalia to ocular surface, potential cytokines involved, and crosstalk cytokines between pterygium and dry eye (DE). This cross-sectional study enrolled 25 healthy controls (HCs) and 116 pterygium patients. Four subgroups of pterygium and DE were used in cytokine evaluations. Conjunctival and pterygium swabs and first-void urine samples (i.e., genitalia samples) were collected for HPV DNA detection using real-time polymerase chain reaction. Tear cytokines interleukin (IL)-6, IL-18, and vascular endothelial growth factor (VEGF) in tears were evaluated. No HPV DNA was detected in conjunctival or pterygium swabs. No association was found between HPV DNA in urine samples and that from conjunctival or pterygium swabs. Tear VEGF levels were significantly higher in pterygium patients than in HCs, with no markedly different levels between primary and recurrent pterygia. Tear IL-6, IL-18, and tear VEGF were significantly higher in participants with DE, regardless of pterygium status. In conclusion, HPV infection was not a pathogenic factor of pterygia. The hypothesis of HPV transmitting from the genitals to ocular surfaces was nullified. Tear VEGF was involved in both pterygia and DE, whereas tear IL-6 and IL-18 played roles only in DE.

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ADAR1 function affects HPV replication and is associated to recurrent human papillomavirus-induced dysplasia in HIV coinfected individuals

Scientific Reports ◽

10.1038/s41598-019-56422-x ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Maria Pujantell ◽

Roger Badia ◽

Iván Galván-Femenía ◽

Edurne Garcia-Vidal ◽

Rafael de Cid ◽

...

Keyword(s):

Human Papillomavirus ◽

Immune Activation ◽

Hpv Infection ◽

Innate Immune ◽

Type I ◽

Innate Immune Activation ◽

Enhanced Expression

AbstractInfection by human papillomavirus (HPV) alters the microenvironment of keratinocytes as a mechanism to evade the immune system. A-to-I editing by ADAR1 has been reported to regulate innate immunity in response to viral infections. Here, we evaluated the role of ADAR1 in HPV infection in vitro and in vivo. Innate immune activation was characterized in human keratinocyte cell lines constitutively infected or not with HPV. ADAR1 knockdown induced an innate immune response through enhanced expression of RIG-I-like receptors (RLR) signaling cascade, over-production of type-I IFNs and pro-inflammatory cytokines. ADAR1 knockdown enhanced expression of HPV proteins, a process dependent on innate immune function as no A-to-I editing could be identified in HPV transcripts. A genetic association study was performed in a cohort of HPV/HIV infected individuals followed for a median of 6 years (range 0.1–24). We identified the low frequency haplotype AACCAT significantly associated with recurrent HPV dysplasia, suggesting a role of ADAR1 in the outcome of HPV infection in HIV+ individuals. In summary, our results suggest that ADAR1-mediated innate immune activation may influence HPV disease outcome, therefore indicating that modification of innate immune effectors regulated by ADAR1 could be a therapeutic strategy against HPV infection.

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Physiological, metabolic and transcriptional postnatal phenotypes ofin vitrofertilization (IVF) in the mouse

Journal of Developmental Origins of Health and Disease ◽

10.1017/s204017441700023x ◽

2017 ◽

Vol 8 (4) ◽

pp. 403-410 ◽

Cited By ~ 17

Author(s):

S. K. Feuer ◽

P. F. Rinaudo

Keyword(s):

Assisted Reproductive Technologies ◽

Biological Significance ◽

Great Majority ◽

Reproductive Technologies ◽

Culture Conditions ◽

Molecular Evidence ◽

Metabolic Dysfunction ◽

Molecular Physiology ◽

The Life Course

Approximately 1–4% of children today are conceived using assisted reproductive technologies (ARTs), includingin vitrofertilization (IVF). IVF is considered safe and the great majority of these children are healthy, yet there is increasing physiological and molecular evidence from animal models that ART is associated with postnatal metabolic and cardiovascular alterations. Understanding the mechanisms underlying these changes and determining whether they have biological significance is of paramount importance for optimizing the design of culture conditions and improving the health of ART children across the life course. In this review, we examine the evidence of molecular changes present in adult tissues of rodent offspring generated by preimplantation manipulation of gametes and embryos. Although embryo manipulationin vitrocan induce common transcriptional effects in the blastocyst, transcriptional and metabolomic signatures in adult IVF tissues are largely tissue-specific. However, there is pervasive evidence of oxidative stress and metabolic dysfunction, indicating a lasting effect of IVF on molecular physiology.

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Linc00426 accelerates lung adenocarcinoma progression by regulating miR-455-5p as a molecular sponge

Cell Death and Disease ◽

10.1038/s41419-020-03259-2 ◽

2020 ◽

Vol 11 (12) ◽

Author(s):

Hongli Li ◽

Qingjie Mu ◽

Guoxin Zhang ◽

Zhixin Shen ◽

Yuanyuan Zhang ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Molecular Mechanisms ◽

Epithelial Mesenchymal Transition ◽

Ectopic Expression ◽

Tumor Development ◽

Biological Significance ◽

Mesenchymal Transition

AbstractIncreasing lines of evidence indicate the role of long non-coding RNAs (LncRNAs) in gene regulation and tumor development. Hence, it is important to elucidate the mechanisms of LncRNAs underlying the proliferation, metastasis, and invasion of lung adenocarcinoma (LUAD). We employed microarrays to screen LncRNAs in LUAD tissues with and without lymph node metastasis and revealed their effects on LUAD. Among them, Linc00426 was selected for further exploration in its expression, the biological significance, and the underlying molecular mechanisms. Linc00426 exhibits ectopic expression in LUAD tissues and cells. The ectopic expression has been clinically linked to tumor size, lymphatic metastasis, and tumor differentiation of patients with LUAD. The deregulation of Linc00426 contributes to a notable impairment in proliferation, invasion, metastasis, and epithelial–mesenchymal transition (EMT) in vitro and in vivo. Mechanistically, the deregulation of Linc00426 could reduce cytoskeleton rearrangement and matrix metalloproteinase expression. Meanwhile, decreasing the level of Linc00426 or increasing miR-455-5p could down-regulate the level of UBE2V1. Thus, Linc00426 may act as a competing endogenous RNA (ceRNA) to abate miR-455-5p-dependent UBE2V1 reduction. We conclude that Linc00426 accelerates LUAD progression by acting as a molecular sponge to regulate miR-455-5p, and may be a potential novel tumor marker for LUAD.

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Role of Regulatory B Cells in the Progression of Cervical Cancer

Mediators of Inflammation ◽

10.1155/2019/6519427 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 5

Author(s):

Zhifang Chen ◽

Yuejie Zhu ◽

Rong Du ◽

Nannan Pang ◽

Fengbo Zhang ◽

...

Keyword(s):

Cervical Cancer ◽

T Cells ◽

Cancer Patients ◽

Intraepithelial Neoplasia ◽

Serum Levels ◽

Hpv Infection ◽

Control Group ◽

Cell Percentage

This study is to investigate the role of regulatory B (Breg) cells in cervical cancer. In total, 70 cases of cervical cancer, 52 cases of cervical intraepithelial neoplasia (CIN), and 40 normal controls were enrolled. The percentage of Breg cells was detected by flow cytometry. Serum levels of IL-10 were measured by ELISA. The correlation between Breg cells and the clinical characterizations of cervical cancer was analyzed. The inhibition effect of Breg cells on CD8+ T cells was tested by blocking IL-10 in vitro. The percentage of CD19+CD5+CD1d+ Breg cells and the level of IL-10 of patients with cervical cancer or CIN were significantly higher than those in the control group (P<0.05). And the postoperative levels of Breg cells and IL-10 were significantly lower than the preoperative levels (P<0.05). Breg cells and the IL-10 level were positively correlated in cervical cancer patients (r=0.516). In addition, the Breg cell percentage was closely related to the FIGO stages, lymph node metastasis, tumor differentiation, HPV infection, and the tumor metastasis of cervical cancer (P<0.05). The Breg cell percentage was negatively correlated with CD8+ T cells of cervical cancer patients (r=‐0.669). The level of IL-10 in the culture supernatant of Bregs treated with CpG was significantly higher than that of non-Bregs (P<0.05). After coculture with Bregs, the quantity of CD8+ T cells to secrete perforin and Granzyme B was significantly decreased, and this effect was reversed after blocking IL-10 by a specific antibody. Breg cells are elevated in cervical cancer and associated with disease progression and metastasis. Moreover, they can inhibit the cytotoxicity of CD8+ T cells.

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Italian observational study on HPV infection, E6, and p16 expression in men with penile cancer

Virology Journal ◽

10.1186/s12985-020-01424-9 ◽

2020 ◽

Vol 17 (1) ◽

Author(s):

Narcisa Muresu ◽

Giovanni Sotgiu ◽

Laura Saderi ◽

Illari Sechi ◽

Antonio Cossu ◽

...

Keyword(s):

Penile Cancer ◽

Tertiary Care ◽

Hpv Infection ◽

Molecular Techniques ◽

Care Hospital ◽

Hpv 16 ◽

Hpv Dna ◽

Diagnosis And Prognosis ◽

Significant Difference

Abstract Background Human Papillomavirus (HPV) infection is one of the most important causes of cancer. It can play a role in cervical and extra-cervical cancers. Penile cancer is rare, even if an increasing trend was recently reported. Aim of the present study was to assess the prevalence and distribution of HPV genotypes in cases of penile cancer diagnosed in Sardinia, Italy. Surrogate markers of HPV infection (i.e., E6 and p16 genes) were also evaluated in all cases. Methods An observational, retrospective study which recruited all cases of penile cancer diagnosed between 2002 and 2019 at a tertiary care hospital in Sardinia, Italy, was carried out. HPV-DNA detection and genotyping were performed by Real-time PCR. Specimens were tested for oncogene E6 mRNA and for p16(INK4a) expression. Results HPV prevalence was 28.1% (9/32); HPV-16 was the most prevalent genotype (7/9, 77.8%). p16INK4a positivity was found in 66.7% of the samples with a statistically significant difference between HPV-positive and -negative groups. E6-transcript was detected in 71% of the HPV-16 positive samples. The overall survival was not statistically different between HPV-positives and -negatives. Discussion The present study confirms the etiologic role of HPV in penile cancer and supports the adoption of vaccination strategies in men and women. Further studies should clarify the diagnostic and prognostic role of E6 and p16 proteins. Conclusion HPV infection can favor the occurrence of penile cancer, whose diagnosis and prognosis could be improved with the implementation of validated molecular techniques.

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HPV infection and endometriosis: a systematic review and meta-analysis

Jornal Brasileiro de Doenças Sexualmente Transmissíveis ◽

10.5327/dst-2177-8264-201931406 ◽

2019 ◽

Vol 31 (4) ◽

pp. 138-142

Author(s):

Geilson Gomes de Oliveira ◽

José Eleutério ◽

Renata Mírian Nunes Eleutério

Keyword(s):

Systematic Review ◽

Bacterial Infections ◽

Meta Analysis ◽

Hpv Infection ◽

Cochrane Library ◽

Sexually Transmitted ◽

Unexposed Control ◽

Relative Risks ◽

Search Terms

Introduction: Recent research has focused on the role of persistent ascending bacterial infections and sexually transmitted infections (STI) as a factor associated to endometriosis. Indeed, some studies investigated the possible role of HPV in endometriosis, but this topic remains inconclusive. Objective:The present study aims to meta-analyze research that assessed the presence of HPV infection in patients with endometriosis. Methods: MEDLINE, Embase, Scopus, LILACS, Cochrane Library, and OpenGrey were searched until February 10th, 2020. Search terms included “endometriosis” and “HPV” without language restrictions. The combined relative risks and 95% confidence interval (95%CI) were calculated, and heterogeneity was assessed with I-square (I2 ). Results: Meta-analysis with low heterogeneity found a relative risk of twice as much in women exposed to HPV in relation to the unexposed control. Conclusion: Results indicate that HPV could be a risk factor for developing endometriosis.

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