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Article ; Online: Interplay Between SOX9, Wnt/β-Catenin and Androgen Receptor Signaling in Castration-Resistant Prostate Cancer

Namrata Khurana / Suresh C. Sikka

International Journal of Molecular Sciences, Vol 20, Iss 9, p

2019 Volume 2066

Abstract: Androgen receptor (AR) signaling plays a key role not only in the initiation of prostate cancer (PCa) but also in its transition to aggressive and invasive castration-resistant prostate cancer (CRPC). However, the crosstalk of AR with other signaling ... ...

Abstract	Androgen receptor (AR) signaling plays a key role not only in the initiation of prostate cancer (PCa) but also in its transition to aggressive and invasive castration-resistant prostate cancer (CRPC). However, the crosstalk of AR with other signaling pathways contributes significantly to the emergence and growth of CRPC. Wnt/β-catenin signaling facilitates ductal morphogenesis in fetal prostate and its anomalous expression has been linked with PCa. β-catenin has also been reported to form complex with AR and thus augment AR signaling in PCa. The transcription factor SOX9 has been shown to be the driving force of aggressive and invasive PCa cells and regulate AR expression in PCa cells. Furthermore, SOX9 has also been shown to propel PCa by the reactivation of Wnt/β-catenin signaling. In this review, we discuss the critical role of SOX9/AR/Wnt/β-catenin signaling axis in the development and progression of CRPC. The phytochemicals like sulforaphane and curcumin that can concurrently target SOX9, AR and Wnt/β-catenin signaling pathways in PCa may thus be beneficial in the chemoprevention of PCa.
Keywords	prostate cancer (PCa) ; castration-resistant prostate cancer (CRPC) ; androgen receptor (AR) ; SOX9 ; Wnt/β-catenin ; sulforaphane (SFN) ; curcumin (CUR) ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	570
Language	English
Publishing date	2019-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A Scientometric Evaluation of COVID-19 and Male Reproductive Research

Manesh Kumar Panner Selvam / Anika Kapoor / Saradha Baskaran / Ajaya Kumar Moharana / Suresh C. Sikka

Clinics and Practice, Vol 13, Iss 6, Pp 1319-

2023 Volume 1330

Abstract: The COVID-19 pandemic due to the SARS-CoV-2 coronavirus showed acute and prolonged effects on human health. In addition, over the past four years, there has been a tremendous surge in COVID-19-related scientific publications, as shown by bibliometric and ...

Abstract	The COVID-19 pandemic due to the SARS-CoV-2 coronavirus showed acute and prolonged effects on human health. In addition, over the past four years, there has been a tremendous surge in COVID-19-related scientific publications, as shown by bibliometric and scientometric studies. However, such analysis of the scientific literature is lacking in the area of male reproduction. The current scientometric study analyzes publication characteristics of articles related to male reproduction and COVID-19 infection. We used the Scopus database to analyze scientometric data (the number of publications, journals, countries, type of documents, and subject area) related to COVID-19 and male reproductive research. Our literature search identified 345 articles related to COVID-19 and male reproductive research. Most of the articles were published in the USA ( n = 72), Italy ( n = 55), and China ( n = 51). Such research was mainly focused around medicine (57.1%), followed by biochemistry, genetics, and molecular biology (25.7%). Also, in the area of male reproduction, only 37.1% ( n = 128) of the articles contributed towards original research, whereas 52.8% ( n = 182) were review articles and editorials focusing more on sexual dysfunction than infertility. Such a small number of studies published on COVID-19-related effects on male reproduction warrants a significant increase in research, which is required to decipher the mechanism(s) underlying SARS-CoV-2 infection-associated impairment of male reproductive function.
Keywords	SARS-CoV-2 ; COVID-19 ; scientometrics ; male reproduction ; male infertility ; Medicine (General) ; R5-920
Subject code	001
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Telomere Signaling and Maintenance Pathways in Spermatozoa of Infertile Men Treated With Antioxidants

Manesh Kumar Panner Selvam / Saradha Baskaran / Suresh C. Sikka

Frontiers in Cell and Developmental Biology, Vol

An in silico Approach Using Bioinformatic Analysis

2021 Volume 9

Abstract: Telomere shortening is considered as a marker of cellular senescence and it is regulated by various signaling pathways. Sperm telomere appears to play important role in its longevity and function. Antioxidant intake has been known to prevent the ... ...

Abstract	Telomere shortening is considered as a marker of cellular senescence and it is regulated by various signaling pathways. Sperm telomere appears to play important role in its longevity and function. Antioxidant intake has been known to prevent the shortening of telomere. In the management of male infertility, antioxidants are commonly used to counterbalance the seminal oxidative stress. It is important to understand how antioxidants treatment may modulate telomere signaling in sperm. In the current study, we have identified 377 sperm proteins regulated by antioxidants based on data mining of published literature. Bioinformatic analysis revealed involvement of 399 upstream regulators and 806 master regulators associated with differentially expressed sperm proteins. Furthermore, upstream regulator analysis indicated activation of kinases (EGFR and MAPK3) and transcription factors (CCNE1, H2AX, MYC, RB1, and TP53). Hence, it is evident that antioxidant supplementation activates molecules associated with telomere function in sperm. The outcome of this in silico study suggests that antioxidant therapy has beneficial effects on certain transcription factors and kinases associated with sperm telomere maintenance and associated signaling pathways that may play an important role in the management of male factor infertility.
Keywords	antioxidants ; bioinformatics ; data mining ; male infertility ; sperm telomere ; upstream regulators ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Recent Publication Trends in Radiotherapy and Male Infertility over Two Decades

Shubhadeep Roychoudhury / Anandan Das / Manesh Kumar Panner Selvam / Saptaparna Chakraborty / Petr Slama / Suresh C. Sikka / Kavindra Kumar Kesari

Frontiers in Cell and Developmental Biology, Vol

A Scientometric Analysis

2022 Volume 10

Abstract: Radiotherapy, a popular cancer management procedure, negatively impacts reproductive health particularly by reducing the fertility potential. The purpose of this study was to analyze the research trend in radiotherapy associated with male infertility ... ...

Abstract	Radiotherapy, a popular cancer management procedure, negatively impacts reproductive health particularly by reducing the fertility potential. The purpose of this study was to analyze the research trend in radiotherapy associated with male infertility over the past 20 years (2000-May 2021). SCOPUS database was used to retrieve relevant scientometric data (publication per year, affiliation, journals, countries, type of document and area of research) for different subgenres of radiotherapy and male infertility. A total of 275 articles were published related to radiotherapy and male infertility, with the United States being the most dominant country in research output in this field. Radiotherapy and male infertility research have shown positive growth over the last two decades. In-depth analysis revealed that publications (n) related to radiotherapy and male infertility research mainly focused its impact on semen parameters (n = 155) and fertility preservation techniques (n = 169). Our scientometric results highlight a limited research focus on the field of radiotherapy and its impact on male reproductive hormones. Furthermore, a significant lack of research was noticed in the area of omics and male reproductive organs linked to radiotherapy. Substantial research is warranted to further decipher the effect of radiotherapy, at molecular level, leading to male infertility.
Keywords	radiotherapy ; infertility ; semen ; reproductive hormones ; omics ; fertility preservation ; Biology (General) ; QH301-705.5
Subject code	001 ; 306
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Current updates on laboratory techniques for the diagnosis of male reproductive failure

Suresh C Sikka / Wayne JG Hellstrom

Asian Journal of Andrology, Vol 18, Iss 3, Pp 392-

2016 Volume 401

Abstract: The incidence of male reproductive failure leading to infertility, whether due to delayed parenthood, environmental issues, genetic factors, drugs, etc., is increasing throughout the world. The diagnosis and prognosis of male subfertility have become a ... ...

Abstract	The incidence of male reproductive failure leading to infertility, whether due to delayed parenthood, environmental issues, genetic factors, drugs, etc., is increasing throughout the world. The diagnosis and prognosis of male subfertility have become a challenge. While the basic semen assessment has been performed for many years, a number of studies question the value of the traditional semen characteristics. This is partly due to inadequate methods and standardization, limited knowledge of technical requirements for quality assurance, and an incomplete understanding of what clinical information a semen assessment can provide. Laboratories currently performing semen and endocrine assessment show great variability. The World Health Organization (WHO) manual for the evaluation of semen has been the core of andrology and fertility evaluation that has helped in further development of this field over many years. These include the physical appearance of the ejaculate, assessments of sperm count, motility, vitality, morphology, and functional aspects of the sperm and semen sample. These tests also include male endocrine profile, biochemical evaluation of the semen, detection of antisperm antibodies in serum, the use of computer-aided sperm analysis (CASA), sperm DNA integrity, and its damage due to oxidative stress. Assisted reproductive techniques (e.g., IVF, ICSI) have shown great success but are too expensive. Further development in this field with newer techniques and extensive training/instructions can improve accuracy and reduce variability, thus maintaining the quality and standards of such an evaluation. There is an urgent need to have standardized training centers and increased awareness in this area of men′s health for reproductive success.
Keywords	male infertility; quality control management; reproductive failure; semen evaluation; World Health Organization manual ; Medicine ; R ; Diseases of the genitourinary system. Urology ; RC870-923
Subject code	630
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Wolters Kluwer Medknow Publications
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A comparative evaluation of semen parameters in pre- and post-Hurricane Katrina human population

Caner Baran / Wayne J Hellstrom / Suresh C Sikka

Asian Journal of Andrology, Vol 17, Iss 4, Pp 676-

2015 Volume 680

Abstract: A natural disaster leading to accumulation of environmental contaminants may have substantial effects on the male reproductive system. Our aim was to compare and assess semen parameters in a normospermic population residing in the Southern Louisiana, USA ...

Abstract	A natural disaster leading to accumulation of environmental contaminants may have substantial effects on the male reproductive system. Our aim was to compare and assess semen parameters in a normospermic population residing in the Southern Louisiana, USA area pre- and post-Hurricane Katrina. We retrospectively evaluated semen analyses data (n = 3452) of 1855 patients who attended the Tulane University Andrology/Fertility Clinic between 1999 and 2013. The study inclusion criteria were men whose semen analyses showed ≥ 1.5 ml volume; ≥15 million ml -1 sperm concentration; ≥39 million total sperm count; ≥40% motility; >30% morphology, with an abstinence interval of 2-7 days. After the inclusion criteria applied to the population, 367 normospermic patients were included in the study. Descriptive statistics and group-based analyses were performed to interpret the differences between the pre-Katrina (Group 1, 1999-2005) and the post-Katrina (Group 2, 2006-2013) populations. There were significant differences in motility, morphology, number of white blood cell, immature germ cell count, pH and presence of sperm agglutination, but surprisingly there were no significant differences in sperm count between the two populations. This long-term comparative analysis further documents that a major natural disaster with its accompanied environmental issues can influence certain semen parameters (e.g., motility and morphology) and, by extension, fertility potential of the population of such areas.
Keywords	gene regulation ; Musashi ; Musashi-1 ; Musashi-2 ; posttranscriptional control ; RNA binding proteins ; spermatogenesis ; splicing ; testis ; translation ; cell fate ; cell stress ; importin ; karyopherin ; nucleocytoplasmic transport ; spermatid ; spermatocyte ; artificial insemination ; biomarker ; fertility ; fertilization ; flow cytometry ; infertility ; nanotechnology ; oocyte activation ; Postacrosomal Sheath WWI Domain Binding Protein ; sperm ; SPTRX3 ; thioredoxin ; ubiquitin ; ATP binding cassette transporters ; albumin ; high-density lipoprotein ; lipid rafts ; membrane fluidity ; membrane microdomains ; membrane packing ; oxysterols ; reverse cholesterol transport ; sterol transporters ; egg ; heat shock protein A2 ; molecular chaperone ; sperm-egg interactions ; dehydrogenases ; oxidases ; peroxiredoxins ; reactive oxygen species ; spermatozoa ; thiols ; thioredoxins ; antigen-presenting cells ; autoimmunity ; dendritic cells ; epididymis ; macrophages ; peripheral tolerance ; sperm maturation ; genomics ; male infertility ; proteomics ; sperm chromatin ; sperm epigenetics ; sperm DNA damage ; paternal genome ; offspring ; chemotaxis ; rheotaxis ; sperm behavior ; sperm motility ; thermotaxis ; apoptosis ; sperm capacitation ; conservation ; cryobiology ; endangered species ; male fertility ; blood-testis barrier ; ectoplasmic specialization ; ezrin ; hypogonadism ; Leydig cell ; oxidative stress ; Sertoli cell ; ultramorphology ; varicocele ; hyperthermia ; seminal plasma biochemical markers ; sperm parameters ; environment ; Hurricane Katrina ; New Orleans area ; normospermic infertile population ; retrospective semen analysis ; Medicine ; R
Subject code	630
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Medknow Publications Pvt Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Clinical relevance of oxidative stress and sperm chromatin damage in male infertility

Marcello Cocuzza / Suresh C. Sikka / Kelly S. Athayde / Ashok Agarwal

International Brazilian Journal of Urology, Vol 33, Iss 5, Pp 603-

an evidence based analysis

2007 Volume 621

Abstract: Oxidative stress (OS) in the reproductive tract is now a real entity and concern due to the potential harmful effects of high levels of reactive oxygen species (ROS) on sperm number, motility, quality, and function including damage to sperm nuclear DNA. ... ...

Abstract	Oxidative stress (OS) in the reproductive tract is now a real entity and concern due to the potential harmful effects of high levels of reactive oxygen species (ROS) on sperm number, motility, quality, and function including damage to sperm nuclear DNA. Evaluation of OS related damage to non-functional sperm is highly relevant as intracytoplasmic sperm injection (ICSI) technique, an effective therapy for severe male factor infertility, bypasses the majority of reproductive tract deficiencies. Despite the controversial findings in the existing literature, there is now enough evidence to show that sperm DNA damage is detrimental to reproductive outcomes. In addition, spermatozoa of infertile men are suggested to carry more DNA damage than do the spermatozoa from fertile men. Besides impairment of fertility such damage is likely to increase the transmission of genetic diseases during the assisted reproductive procedures. Standardization of protocols to assess reactive oxygen species and DNA damage is very important in introducing these tests in such clinical practice. Thus evaluation of seminal ROS levels and extent of sperm DNA damage especially in an infertile male may help develop new therapeutic strategies and improve success of assisted reproductive techniques (ART).
Keywords	free radicals ; oxidative stress ; sperm ; DNA ; antioxidants ; male infertility ; Diseases of the genitourinary system. Urology ; RC870-923 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Urology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	612
Language	English
Publishing date	2007-10-01T00:00:00Z
Publisher	Sociedade Brasileira de Urologia
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Nrf1 and Nrf2 transcription factors regulate androgen receptor transactivation in prostate cancer cells.

Michelle A Schultz / Sharika S Hagan / Amrita Datta / Yiguo Zhang / Michael L Freeman / Suresh C Sikka / Asim B Abdel-Mageed / Debasis Mondal

PLoS ONE, Vol 9, Iss 1, p e

2014 Volume 87204

Abstract: Despite androgen deprivation therapy (ADT), persistent androgen receptor (AR) signaling enables outgrowth of castration resistant prostate cancer (CRPC). In prostate cancer (PCa) cells, ADT may enhance AR activity through induction of oxidative stress. ... ...

Abstract	Despite androgen deprivation therapy (ADT), persistent androgen receptor (AR) signaling enables outgrowth of castration resistant prostate cancer (CRPC). In prostate cancer (PCa) cells, ADT may enhance AR activity through induction of oxidative stress. Herein, we investigated the roles of Nrf1 and Nrf2, transcription factors that regulate antioxidant gene expression, on hormone-mediated AR transactivation using a syngeneic in vitro model of androgen dependent (LNCaP) and castration resistant (C4-2B) PCa cells. Dihydrotestosterone (DHT) stimulated transactivation of the androgen response element (ARE) was significantly greater in C4-2B cells than in LNCaP cells. DHT-induced AR transactivation was coupled with higher nuclear translocation of p65-Nrf1 in C4-2B cells, as compared to LNCaP cells. Conversely, DHT stimulation suppressed total Nrf2 levels in C4-2B cells but elevated total Nrf2 levels in LNCaP cells. Interestingly, siRNA mediated silencing of Nrf1 attenuated AR transactivation while p65-Nrf1 overexpression enhanced AR transactivation. Subsequent studies showed that Nrf1 physically interacts with AR and enhances AR's DNA-binding activity, suggesting that the p65-Nrf1 isoform is a potential AR coactivator. In contrast, Nrf2 suppressed AR-mediated transactivation by stimulating the nuclear accumulation of the p120-Nrf1 which suppressed AR transactivation. Quantitative RT-PCR studies further validated the inductive effects of p65-Nrf1 isoform on the androgen regulated genes, PSA and TMPRSS2. Therefore, our findings implicate differential roles of Nrf1 and Nrf2 in regulating AR transactivation in PCa cells. Our findings also indicate that the DHT-stimulated increase in p65-Nrf1 and the simultaneous suppression of both Nrf2 and p120-Nrf1 ultimately facilitates AR transactivation in CRPC cells.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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