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https://www.readbyqxmd.com/read/28339648/three-dimensional-testicular-organoid-a-novel-tool-for-the-study-of-human-spermatogenesis-and-gonadotoxicity-in-vitro%C3%A2
#1
Samuel S Pendergraft, Hooman Sadri-Ardekani, Anthony Atala, Colin E Bishop
Existing methods for evaluating the potential gonadotoxicity of environmental agents and pharmaceutical compounds rely heavily on animal studies. The current gold standard in vivo functional assays in animals are limited in their human predictive capacity. In addition, existing human two-dimensional in vitro models of testicular toxicity do not accurately reflect the in vivo situation. A more reliable testicular in vitro model system is needed to better assess the gonadotoxic potential of drugs prior to progression into clinical trials...
February 17, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28339196/discovery-of-a-small-molecule-degrader-of-bromodomain-and-extra-terminal-bet-proteins-with-picomolar-cellular-potencies-and-capable-of-achieving-tumor-regression
#2
Bing Zhou, Jiantao Hu, Fuming Xu, Zhuo Chen, Longchuan Bai, Ester Fernandez-Salas, Mei Lin, Liu Liu, Chao-Yie Yang, Yujun Zhao, Donna McEachern, Sally Przybranowski, Bo Wen, Duxin Sun, Shaomeng Wang
The bromodomain and extra-terminal (BET) family proteins, consisting of BRD2, BRD3, BRD4, and testis-specific BRDT members, are epigenetic "readers" and play a key role in the regulation of gene transcription. BET proteins are considered to be attractive therapeutic targets for cancer and other human diseases. Recently, heterobifunctional small-molecule BET degraders have been designed based upon the proteolysis targeting chimera (PROTAC) concept to induce BET protein degradation. Herein, we present our design, synthesis, and evaluation of a new class of PROTAC BET degraders...
March 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28333312/establishment-maintenance-and-functional-integrity-of-the-blood-testis-barrier-in-organotypic-cultures-of-fresh-and-frozen-thawed-prepubertal-mouse-testes
#3
C Rondanino, A Maouche, L Dumont, A Oblette, N Rives
STUDY QUESTION: Can the spatio-temporal formation of an intact blood-testis barrier (BTB), which is essential for the progression of spermatogenesis, be reproduced in cultures of fresh or frozen/thawed prepubertal mouse testes? SUMMARY ANSWER: Organotypic cultures allow the establishment and maintenance of major BTB components and the formation of a functional BTB in mouse testicular tissues. WHAT IS KNOWN ALREADY: In vitro maturation of prepubertal testicular tissues is a promising approach to restore fertility in adult survivors of childhood cancer...
March 17, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28333300/comparison-of-global-gene-expression-profiles-of-microdissected-human-foetal-leydig-cells-with-their-normal-and-hyperplastic-adult-equivalents
#4
Grete Lottrup, Kirstine Belling, Henrik Leffers, John E Nielsen, Marlene D Dalgaard, Anders Juul, Niels E Skakkebæk, Søren Brunak, Ewa Rajpert-De Meyts
STUDY QUESTION: Do human adult Leydig cells (ALCs) within hyperplastic micronodules display characteristics of foetal LCs (FLCs)? SUMMARY ANSWER: The gene expression profiles of FLCs and all ALC subgroups were clearly different, but there were no significant differences in expressed genes between the normally clustered and hyperplastic ALCs. WHAT IS KNOWN ALREADY: LCs are the primary androgen producing cells in males throughout development and appear in chronologically distinct populations; FLCs, neonatal LCs and ALCs...
March 17, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28333256/analgesia-use-during-pregnancy-and-risk-of-cryptorchidism-a-systematic-review-and-meta-analysis
#5
Jason Gurney, Lorenzo Richiardi, Katherine A McGlynn, Virginia Signal, Diana Sarfati
STUDY QUESTION: Are boys who are born to mothers who use analgesics during pregnancy at increased risk of cryptorchidism compared to those born to mothers who do not take analgesia? SUMMARY ANSWER: In this systematic review and meta-analysis of 10 published studies, we observed only weak evidence of an association between analgesia use during pregnancy and risk of cryptorchidism in the son. WHAT IS KNOWN ALREADY: Concentrations of analgesia relevant to human exposure have been implicated as causing endocrine disturbances in the developing foetal testis...
March 8, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28300557/high-fat-diet-aggravates-2-2-4-4-tetrabromodiphenyl-ether-inhibited-testosterone-production-via-dax-1-in-leydig-cells-in-rats
#6
Zhan Zhang, Yongquan Yu, Hengsen Xu, Chao Wang, Minghui Ji, Jun Gu, Lu Yang, Jiansheng Zhu, Huibin Dong, Shou-Lin Wang
Growing evidence has revealed that a high-fat diet (HFD) could lead to disorders of glycolipid metabolism and insulin-resistant states, and HFDs have been associated with the inhibition of testicular steroidogenesis. Our previous study demonstrated that 2,2',4,4'-tetrabromodiphenyl ether (BDE47) could increase the risk of diabetes in humans and reduce testosterone production in rats. However, whether the HFD affects BDE47-inhibited testosterone production by elevating insulin levels and inducing related pathways remains unknown...
March 12, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28291811/systematic-identification-and-characterization-of-long-non-coding-rnas-in-mouse-mature-sperm
#7
Xiaoning Zhang, Fengxin Gao, Jianbo Fu, Peng Zhang, Yuqing Wang, Xuhui Zeng
Increasing studies have shown that mature spermatozoa contain many transcripts including mRNAs and miRNAs. However, the expression profile of long non-coding RNAs (lncRNAs) in mammalian sperm has not been systematically investigated. Here, we used highly purified RNA to investigate lncRNA expression profiles in mouse mature sperm by stranded-specific RNA-seq. We identified 20,907 known and 4,088 novel lncRNAs transcripts, and the existence of intact lncRNAs was confirmed by RT-PCR and fluorescence in situ hybridization on two representative lncRNAs...
2017: PloS One
https://www.readbyqxmd.com/read/28289609/the-regenerative-effect-of-bone-marrow-derived-stem-cells-in-spermatogenesis-of-infertile-hamster
#8
Akbar Vahdati, Alireza Fathi, Mehrdokht Hajihoseini, Ghaem Aliborzi, Ebrahim Hosseini
BACKGROUND: Infertility is a serious social problem in advanced nations, with male factor in half of all cases of infertility. This study was conducted to determine the regenerative effect of bone marrow-derived stem cells in spermatogenesis of infertile hamster. METHODS: Twelve adult male hamsters were equally divided into azoospermic and control groups. Busulfan was intraperitoneally used for induction of azoospermia, while the right testis was treated with bone marrow-derived stem cells (10(6) BM-SCs), labeled with sterile trypan blue, 35 days after busulfan injection...
January 2017: World Journal of Plastic Surgery
https://www.readbyqxmd.com/read/28281692/ibuprofen-results-in-alterations-of-human-fetal-testis-development
#9
Millissia Ben Maamar, Laurianne Lesné, Kristin Hennig, Christèle Desdoits-Lethimonier, Karen R Kilcoyne, Isabelle Coiffec, Antoine D Rolland, Cécile Chevrier, David M Kristensen, Vincent Lavoué, Jean-Philippe Antignac, Bruno Le Bizec, Nathalie Dejucq-Rainsford, Rod T Mitchell, Séverine Mazaud-Guittot, Bernard Jégou
Among pregnant women ibuprofen is one of the most frequently used pharmaceutical compounds with up to 28% reporting use. Regardless of this, it remains unknown whether ibuprofen could act as an endocrine disruptor as reported for fellow analgesics paracetamol and aspirin. To investigate this, we exposed human fetal testes (7-17 gestational weeks (GW)) to ibuprofen using ex vivo culture and xenograft systems. Ibuprofen suppressed testosterone and Leydig cell hormone INSL3 during culture of 8-9 GW fetal testes with concomitant reduction in expression of the steroidogenic enzymes CYP11A1, CYP17A1 and HSD17B3, and of INSL3...
March 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28278534/transcription-and-splicing-factor-tdp-43-role-in-regulation-of-gene-expression-in-testis
#10
Prabhakara P Reddi
TDP-43 (TAR DNA binding Protein of 43 kD) is a transcription factor and RNA-binding protein with diverse functions. We cloned TDP-43 from the mouse testis in a screen for promoter-binding proteins and showed that it functions as a transcriptional repressor. TDP-43 plays a role in maintaining the precise pattern of spatiotemporal expression of the spermatid-specific Acrv1 gene during spermatogenesis by facilitating RNA polymerase II pausing at the promoter. We also showed that TDP-43 plays a partial role in preventing somatic cell expression of the Acrv1 gene by acting as an insulator-binding protein...
March 2017: Seminars in Reproductive Medicine
https://www.readbyqxmd.com/read/28277341/analgesic-use-in-pregnancy-and-male-reproductive-development
#11
Pablo Hurtado-Gonzalez, Rod T Mitchell
PURPOSE OF REVIEW: Male reproductive disorders are common and increasing in incidence in many countries. Environmental factors (including pharmaceuticals) have been implicated in the development of these disorders. This review aims to summarize the emerging epidemiological and experimental evidence for a potential role of in-utero exposure to analgesics in the development of male reproductive disorders. RECENT FINDINGS: A number of epidemiological studies have demonstrated an association between in utero exposure to analgesics and the development of cryptorchidism, although these findings are not consistent across all studies...
March 8, 2017: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/28272493/effects-of-different-kinds-of-essentiality-on-sequence-evolution-of-human-testis-proteins
#12
Julia Schumacher, Hans Zischler, Holger Herlyn
We asked if essentiality for either fertility or viability differentially affects sequence evolution of human testis proteins. Based on murine knockout data, we classified a set of 965 proteins expressed in human seminiferous tubules into three categories: proteins essential for prepubertal survival ("lethality proteins"), associated with male sub- or infertility ("male sub-/infertility proteins"), and nonessential proteins. In our testis protein dataset, lethality genes evolved significantly slower than nonessential and male sub-/infertility genes, which is in line with other authors' findings...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28264506/plasma-membrane-na%C3%A2-%C2%BA-coupled-citrate-transporter-slc13a5-and-neonatal-epileptic-encephalopathy
#13
REVIEW
Yangzom D Bhutia, Jonathan J Kopel, John J Lawrence, Volker Neugebauer, Vadivel Ganapathy
SLC13A5 is a Na⁺-coupled transporter for citrate that is expressed in the plasma membrane of specific cell types in the liver, testis, and brain. It is an electrogenic transporter with a Na⁺:citrate(3-) stoichiometry of 4:1. In humans, the Michaelis constant for SLC13A5 to transport citrate is ~600 μM, which is physiologically relevant given that the normal concentration of citrate in plasma is in the range of 150-200 μM. Li⁺ stimulates the transport function of human SLC13A5 at concentrations that are in the therapeutic range in patients on lithium therapy...
February 28, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28255005/international-union-of-basic-and-clinical-pharmacology-ci-structures-and-small-molecule-modulators-of-mammalian-adenylyl-cyclases
#14
REVIEW
Carmen W Dessauer, Val J Watts, Rennolds S Ostrom, Marco Conti, Stefan Dove, Roland Seifert
Adenylyl cyclases (ACs) generate the second messenger cAMP from ATP. Mammalian cells express nine transmembrane AC (mAC) isoforms (AC1-9) and a soluble AC (sAC, also referred to as AC10). This review will largely focus on mACs. mACs are activated by the G-protein Gαs and regulated by multiple mechanisms. mACs are differentially expressed in tissues and regulate numerous and diverse cell functions. mACs localize in distinct membrane compartments and form signaling complexes. sAC is activated by bicarbonate with physiologic roles first described in testis...
April 2017: Pharmacological Reviews
https://www.readbyqxmd.com/read/28250657/short-term-effects-of-date-palm-extract-phoenix-dactylifera-on-ischemia-reperfusion-injury-induced-by-testicular-torsion-detorsion-in-rats
#15
Alireza Raayat Jahromi, Rokhsana Rasooli, Younes Kamali, Nasrollah Ahmadi, Ehsan Sattari
BACKGROUND: Antioxidants are potent scavengers of free radicals and have beneficial effects on human health. OBJECTIVE: The aim of this study was to investigate the potential protective antioxidant activity of the edible portion of date fruit extract in an experimental testicular torsion/detorsion (T/D) model in rats. MATERIALS AND METHODS: To investigate the potential protective effects of date palm (DP), 30 male Spraque-Dawley rats were divided into three groups: sham-operated, T/D, and T/D + DP-treated (500 mg/kg, PO) groups...
January 2017: Pharmacognosy Research
https://www.readbyqxmd.com/read/28250650/chronic-intake-of-green-propolis-negatively-affecting-the-rat-testis
#16
Grasiela Dias de Campos Severi-Aguiar, Suellen Josine Pinto, Cristina Capucho, Camila Andrea Oliveira, Maria Aparecida Diamante, Renata Barbieri, Fabrícia Souza Predes, Heidi Dolder
BACKGROUND: Human and animal evidence suggests that environmental toxicants may have an adverse impact on male reproductive health, reducing the population's reproductive output. Owing to the renewed attraction for natural products, some of them constitute effective alternatives to mitigate these effects. Propolis is a candidate for this use because of its intrinsic properties. In many situations, it improved the testicular damage and alleviated the toxic effects induced by environmental contaminant exposure...
January 2017: Pharmacognosy Research
https://www.readbyqxmd.com/read/28248963/brother-of-the-regulator-of-the-imprinted-site-boris-variant-subfamily-6-is-a-novel-target-of-lung-cancer-stem-like-cell-immunotherapy
#17
Ryota Horibe, Yoshihiko Hirohashi, Takuya Asano, Tasuku Mariya, Takeshi Suzuki, Akari Takaya, Hiroshi Saijo, Yosuke Shionoya, Terufumi Kubo, Munehide Nakatsugawa, Takayuki Kanaseki, Tomohide Tsukahara, Kazue Watanabe, Eri Atsuyama, Shingo Toji, Hiroshi Hirano, Tadashi Hasegawa, Hiroki Takahashi, Noriyuki Sato, Toshihiko Torigoe
Lung cancer is one of the most common malignancies with a high rate of mortality. Lung cancer stem-like cells (CSCs)/ cancer-initiating cells (CICs) play major role in resistance to treatments, recurrence and distant metastasis and eradication of CSCs/CICs is crucial to improve recent therapy. Cytotoxic T lymphocytes (CTLs) are major effectors of cancer immunotherapy, and CTLs recognize antigenic peptides derived from antigens that are presented by major histocompatibility complex (MHC) class I molecules. In this study, we analyzed the potency of a cancer-testis (CT) antigen, brother of the regulator of the imprinted site variant subfamily 6 (BORIS sf6), in lung CSC/CIC immunotherapy...
2017: PloS One
https://www.readbyqxmd.com/read/28247052/sperm-navigation-mechanisms-in-the-female-reproductive-tract
#18
Hieu D Hoang, Michael A Miller
Fertilization, the union of an oocyte and a sperm, is a fundamental process that restores the diploid genome and initiates embryonic development. For the sperm, fertilization is the end of a long journey, one that starts in the male testis before transitioning to the female reproductive tract's convoluted tubule architecture. Historically, motile sperm were thought to complete this journey using luck and numbers. A different picture of sperm has emerged recently as cells that integrate complex sensory information for navigation...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/28245420/-reseach-advances-on-cancer-testis-antigens-in-multiple-myeloma-review
#19
Zhi-Rui Yang, Li Yu, Hai-Yan Zhu
Cancer-testis antigens (CTA) are a class of tumor-associated antigens, which are mainly located in X chromosome. CTA restrictively expressed in normal testis, ovary, placenta and so on. Their expression in other normal tissues is much lower, even can not be detected. However, their expressions are aberrantly high in human cancers. Based on CTA encoding immunogenic proteins, they can be regulated by epigentics, CTA provides very attractive targets for cancer immunotherapy. Multiple myeloma (MM) is incurable and has a low cureative rate and a high relapse rate...
February 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28242272/estrogen-dependent-extrahepatic-synthesis-of-vitellogenin-in-male-vertebrates-a-mini-review
#20
Mariailaria Verderame, Rosaria Scudiero
In the last years, the hormonal balance is threatened by the interferences of substances with hormone-like action (endocrine disruptor chemicals, EDCs) that may harm animal reproduction. Most EDCs are resistant to environmental degradation and are considered ubiquitous contaminants. EDCs may have synthetic or natural origins. Pesticides used in intensive agriculture contain large amounts of chemicals with estrogenic properties, such as the alkylphenol nonylphenol (NP). Besides, animal feeding operations are important sources of natural estrogen metabolites introduced into the environment through manure application in organic farming...
February 24, 2017: Comptes Rendus Biologies
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