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https://www.readbyqxmd.com/read/28426816/ex-vivo-cultures-combined-with-vivo-morpholino-induced-gene-knockdown-provide-a-system-to-assess-the-role-of-wt1-and-gata4-during-gonad-differentiation
#1
Lucas J Rudigier, Christof Dame, Holger Scholz, Karin M Kirschner
Gonad morphogenesis relies on the correct spatiotemporal expression of a number of genes that together fulfill the differentiation of the bipotential gonad into testes or ovaries. As such, the transcription factors WT1 and GATA4 are pivotal for proper gonadal development. Here we address the contributions of GATA4 and WT1 to the sex differentiation phase in testes and ovaries. We applied an ex vivo technique for cultivating gonads in hanging droplets of media that were supplemented with vivo-morpholinos to knockdown WT1 and GATA4 either alone or in combination at the same developmental stage...
2017: PloS One
https://www.readbyqxmd.com/read/28397607/sex-reversal-and-analyses-of-possible-involvement-of-sex-steroids-in-scallop-gonadal-development-in-newly-established-organ-culture-systems
#2
Ayano Otani, Tadaaki Nakajima, Tomomi Okumura, Shiro Fujii, Yasuhiro Tomooka
Many molluscs perform sex reversal, and sex hormones may be involved in the process. In adult scallops, Patinopecten yessoensis, gonadotropin releasing hormone and 17β-estradiol (E2) are involved in male sexual maturation, however, little is known about the effects of E2 and testosterone (T) on the gonadal differentiation in young scallops. In the present study, scallop gonadal development was analyzed to determine the sex reversal stage in Funka bay, and effects of E2 and T were examined. In Funka bay, almost all scallops were male at month 12...
April 2017: Zoological Science
https://www.readbyqxmd.com/read/28397603/masculinization-related-genes-and-cell-mass-structures-during-early-gonadal-differentiation-in-the-african-clawed-frog-xenopus-laevis
#3
Mikako Wada, Kazuko Fujitani, Kei Tamura, Shuuji Mawaribuchi, Yosuke Kamata, Nobuhiko Takamatsu, Michihiko Ito
The African clawed frog Xenopus laevis has a female heterogametic ZZ/ZW-type sex-determining system. We previously discovered a W-linked female sex-determining gene dm-W that is involved in ovary formation, probably through the up-regulation of the estrogen synthesis genes cyp19a1 and foxl2. We also reported that a unique "mass-in-line structure", which disappears from ZZ gonads during early testicular development, might serve as the basis for ovary differentiation in ZW gonads. However, the molecular mechanisms underlying early masculinization are poorly understood...
April 2017: Zoological Science
https://www.readbyqxmd.com/read/28377632/integrated-analysis-of-gene-expression-and-copy-number-identified-potential-cancer-driver-genes-with-amplification-dependent-overexpression-in-1-454-solid-tumors
#4
Keiichi Ohshima, Keiichi Hatakeyama, Takeshi Nagashima, Yuko Watanabe, Kaori Kanto, Yuki Doi, Tomomi Ide, Yuji Shimoda, Tomoe Tanabe, Sumiko Ohnami, Shumpei Ohnami, Masakuni Serizawa, Koji Maruyama, Yasuto Akiyama, Kenichi Urakami, Masatoshi Kusuhara, Tohru Mochizuki, Ken Yamaguchi
Identification of driver genes contributes to the understanding of cancer etiology and is imperative for the development of individualized therapies. Gene amplification is a major event in oncogenesis. Driver genes with tumor-specific amplification-dependent overexpression can be therapeutic targets. In this study, we aimed to identify amplification-dependent driver genes in 1,454 solid tumors, across more than 15 cancer types, by integrative analysis of gene expression and copy number. Amplification-dependent overexpression of 64 known driver oncogenes were found in 587 tumors (40%); genes frequently observed were MYC (25%) and MET (18%) in colorectal cancer; SKP2 (21%) in lung squamous cell carcinoma; HIST1H3B (19%) and MYCN (13%) in liver cancer; KIT (57%) in gastrointestinal stromal tumors; and FOXL2 (12%) in squamous cell carcinoma across tissues...
April 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28347743/transcription-of-cyp19a1-is-directly-regulated-by-sf-1-in-the-theca-cells-of-ovary-follicles-in-chicken
#5
Jing Wang, Yanzhang Gong
Many studies have suggested the important role of estrogen in ovarian differentiation and development of vertebrates including chicken. Cytochrome P450 aromatase, encoded by CYP19A1, is a key enzyme in estrogen synthesis, but the mechanism of CYP19A1 regulation in chicken remains unknown. Here, we found that CYP19A1 was only expressed in the theca cell layers of chicken ovary follicles. Steroidogenic factor 1 (SF-1, also named as nuclear receptor subfamily 5 group A member 1, NR5A1), a potential regulators, was expressed in both the theca cell layers and granulosa cell layers...
March 24, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28347324/pms2-gene-mutation-results-in-dna-mismatch-repair-system-failure-in-a-case-of-adult-granulosa-cell-tumor
#6
Wen-Chung Wang, Ya-Ting Lee, Yen-Chein Lai
BACKGROUND: Granulosa cell tumors are rare ovarian malignancies. Their characteristics include unpredictable indolent growth with malignant potential and late recurrence. Approximately 95% are of adult type. Recent molecular studies have characterized the FOXL2 402C > G mutation in adult granulosa cell tumor. Our previous case report showed that unique FOXL2 402C > G mutation and defective DNA mismatch repair system are associated with the development of adult granulosa cell tumor...
March 27, 2017: Journal of Ovarian Research
https://www.readbyqxmd.com/read/28319575/foxl2-mutation-status-in-granulosa-theca-cell-tumors-of-the-ovary
#7
Amber Nolan, Nancy M Joseph, Ankur R Sangoi, Joseph Rabban, Charles Zaloudek, Karuna Garg
Ovarian sex-cord stromal tumors that have between 10% and 50% granulosa cells in a prominent fibrothecomatous background have been referred to as granulosa theca cell tumors or mixed granulosa theca cell tumors. The classification and prognosis of these tumors is not clear. Most adult granulosa cell tumors of the ovary harbor a mutation in the FOXL2 gene, whereas fibromas and thecomas lack this mutation. The aim of our study was to assess the FOXL2 mutation status of ovarian granulosa theca cell tumors and to correlate the mutation status with morphologic and clinical characteristics...
March 17, 2017: International Journal of Gynecological Pathology
https://www.readbyqxmd.com/read/28296881/transcriptomic-responses-to-environmental-temperature-by-turtles-with-temperature-dependent-and-genotypic-sex-determination-assessed-by-rnaseq-inform-the-genetic-architecture-of-embryonic-gonadal-development
#8
Srihari Radhakrishnan, Robert Literman, Jennifer Neuwald, Andrew Severin, Nicole Valenzuela
Vertebrate sexual fate is decided primarily by the individual's genotype (GSD), by the environmental temperature during development (TSD), or both. Turtles exhibit TSD and GSD, making them ideal to study the evolution of sex determination. Here we analyze temperature-specific gonadal transcriptomes (RNA-sequencing validated by qPCR) of painted turtles (Chrysemys picta TSD) before and during the thermosensitive period, and at equivalent stages in soft-shell turtles (Apalone spinifera-GSD), to test whether TSD's and GSD's transcriptional circuitry is identical but deployed differently between mechanisms...
2017: PloS One
https://www.readbyqxmd.com/read/28276867/pathogenesis-and-treatment-of-adult-type-granulosa-cell-tumor-of-the-ovary
#9
Anniina Färkkilä, Ulla-Maija Haltia, Johanna Tapper, Melissa K McConechy, David G Huntsman, Markku Heikinheimo
Adult-type granulosa cell tumor is a clinically and molecularly unique subtype of ovarian cancer. These tumors originate from the sex cord stromal cells of the ovary and represent 3-5% of all ovarian cancers. The majority of adult-type granulosa cell tumors are diagnosed at an early stage with an indolent prognosis. Surgery is the cornerstone for the treatment of both primary and relapsed tumor, while chemotherapy is applied only for advanced or non-resectable cases. Tumor stage is the only factor consistently associated with prognosis...
March 6, 2017: Annals of Medicine
https://www.readbyqxmd.com/read/28272677/correlation-of-foxl2-with-inhibin-and-calretinin-in-the-diagnosis-of-ovarian-sex-cord-stromal-tumors
#10
Ruchi Rathore, Deepshikha Arora, Sarla Agarwal, Sonal Sharma
OBJECTIVE: Alpha-inhibin and calretinin have been traditionally used as immunomarkers for sex cord stromal tumors. However, the variation in their immunoreactivity and their lack of specificity for sex cord stromal tumor makes the search for a more sensitive and specific immunohistochemical marker essential in routine diagnosis of sex cord stromal tumor. This study was conducted to correlate the diagnostic utility of FOXL2 with inhibin and calretinin in the diagnosis of sex cord stromal tumors of ovary...
February 4, 2017: Türk Patoloji Dergisi
https://www.readbyqxmd.com/read/28209164/rnf40-regulates-gene-expression-in-an-epigenetic-context-dependent-manner
#11
Wanhua Xie, Sankari Nagarajan, Simon J Baumgart, Robyn Laura Kosinsky, Zeynab Najafova, Vijayalakshmi Kari, Magali Hennion, Daniela Indenbirken, Stefan Bonn, Adam Grundhoff, Florian Wegwitz, Ahmed Mansouri, Steven A Johnsen
BACKGROUND: Monoubiquitination of H2B (H2Bub1) is a largely enigmatic histone modification that has been linked to transcriptional elongation. Because of this association, it has been commonly assumed that H2Bub1 is an exclusively positively acting histone modification and that increased H2Bub1 occupancy correlates with increased gene expression. In contrast, depletion of the H2B ubiquitin ligases RNF20 or RNF40 alters the expression of only a subset of genes. RESULTS: Using conditional Rnf40 knockout mouse embryo fibroblasts, we show that genes occupied by low to moderate amounts of H2Bub1 are selectively regulated in response to Rnf40 deletion, whereas genes marked by high levels of H2Bub1 are mostly unaffected by Rnf40 loss...
February 16, 2017: Genome Biology
https://www.readbyqxmd.com/read/28208728/parabens-accelerate-ovarian-dysfunction-in-a-4-vinylcyclohexene-diepoxide-induced-ovarian-failure-model
#12
Jae-Hwan Lee, Myeongho Lee, Changhwan Ahn, Hee Young Kang, Dinh Nam Tran, Eui-Bae Jeung
Parabens are widely used preservatives in basic necessities such as cosmetic and pharmaceutical products. In previous studies, xenoestrogenic actions of parabens were reported in an immature rat model and a rat pituitary cell line (GH3 cells). The relationship between parabens and ovarian failure has not been described. In the present study, the influence of parabens on ovarian folliculogenesis and steroidogenesis was investigated. A disruptor of ovarian small pre-antral follicles, 4-vinylcyclohexene diepoxide (VCD, 40 mg/kg), was used to induce premature ovarian failure (POF)...
February 8, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28205594/genome-editing-reveals-dmrt1-as-an-essential-male-sex-determining-gene-in-chinese-tongue-sole-cynoglossus-semilaevis
#13
Zhongkai Cui, Yun Liu, Wenwen Wang, Qian Wang, Ning Zhang, Fan Lin, Na Wang, Changwei Shao, Zhongdian Dong, Yangzhen Li, Yingming Yang, Mengzhu Hu, Hailong Li, Fengtao Gao, Zhanfei Wei, Liang Meng, Yang Liu, Min Wei, Ying Zhu, Hua Guo, Christopher H K Cheng, Manfred Schartl, Songlin Chen
Chinese tongue sole is a marine fish with ZW sex determination. Genome sequencing suggested that the Z-linked dmrt1 is a putative male determination gene, but direct genetic evidence is still lacking. Here we show that TALEN of dmrt1 efficiently induced mutations of this gene. The ZZ dmrt1 mutant fish developed ovary-like testis, and the spermatogenesis was disrupted. The female-related genes foxl2 and cyp19a1a were significantly increased in the gonad of the ZZ dmrt1 mutant. Conversely, the male-related genes Sox9a and Amh were significantly decreased...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28193729/sequential-divergent-and-cooperative-requirements-of-foxl2a-and-foxl2b-in-ovary-development-and-maintenance-of-zebrafish
#14
Yan-Jing Yang, Yang Wang, Zhi Li, Li Zhou, Jian-Fang Gui
Foxl2 is essential for mammalian ovary maintenance. Although sexually dimorphic expression of foxl2 was observed in many teleosts, its role and regulative mechanism in fish remained largely unclear. In this study, we first identified two transcript variants of foxl2a and its homologous gene foxl2b in zebrafish, and revealed their specific expression in follicular layer cells in a sequential and divergent fashion during ovary differentiation, maturation, and maintenance. Then, homozygous foxl2a mutants (foxl2a(-/-)) and foxl2b mutants (foxl2b(-/-)) were constructed and detailed comparisons, such as sex ratio, gonadal histological structure, transcriptome profiling, and dynamic expression of gonadal development-related genes, were carried out...
April 2017: Genetics
https://www.readbyqxmd.com/read/28166983/maternal-recognition-of-pregnancy-and-implantation-are-not-associated-with-an-interferon-response-of-the-endometrium-to-the-presence-of-the-conceptus-in-dromedary-camel
#15
Ahmed Sabry Salah Abdoon, Corrine Giraud-Delville, Omaima Mohamed Kandil, Annelye Kerboeuf-Giraud, Caroline Eozénou, Anais Vitorino Carvalho, Skidmore Julian, Olivier Sandra
Maternal recognition of pregnancy (MRP) and implantation involve appropriate interactions between the elongating conceptus and the receptive endometrium that will condition development of the feto-placental unit to term. Molecular mechanisms that take place at the conceptus-endometrium interface during early pregnancy have been extensively investigated in domestic ungulates but they are still poorly understood in camelids including the dromedary camel (Camelus dromedarius), a domestic species with important economic and social roles in arid and semi-arid areas...
March 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28154936/cultured-bovine-granulosa-cells-rapidly-lose-important-features-of-their-identity-and-functionality-but-partially-recover-under-long-term-culture-conditions
#16
Vengala Rao Yenuganti, Jens Vanselow
Cell culture models are essential for the detailed study of molecular processes. We analyze the dynamics of changes in a culture model of bovine granulosa cells. The cells were cultured for up to 8 days and analyzed for steroid production and gene expression. According to the expression of the marker genes CDH1, CDH2 and VIM, the cells maintained their mesenchymal character throughout the time of culture. In contrast, the levels of functionally important transcripts and of estradiol and progesterone production were rapidly down-regulated but showed a substantial up-regulation from day 4...
February 2, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28119367/hmga2-foxl2-axis-regulates-metastases-and-epithelial-to-mesenchymal-transition-of-chemo-resistant-gastric-cancer
#17
Jiaqiang Dong, Rui Wang, Gui Ren, Xiaowei Li, Jingbo Wang, Yi Sun, Jie Liang, Yongzan Nie, Kaichun Wu, Bin Feng, Yulong Shang, Daiming Fan
Purpose Chemo-resistance is the main cause of treatment failure in cancer and is associated with distant metastases and epithelial-to-mesenchymal transition (EMT). This study aimed to explore the mechanism of metastases and EMT in chemo-resistant gastric cancer (GC). Experimental Design A key molecular pathway was identified via gene profiling and a bioinformatic analysis in a chemo-resistant GC model. The roles of FOXL2, HMGA2 and ITGA2 were validated via loss-of-function and gain-of-function experiments in vitro and in an orthotopic GC animal model...
January 24, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28091399/sex-determination-and-maintenance-the-role-of-dmrt1-and-foxl2
#18
REVIEW
Shengsong Huang, Leping Ye, Haolin Chen
In many species, including mammals, sex determination is genetically based. The sex chromosomes that individuals carry determine sex identity. Although the genetic base of phenotypic sex is determined at the moment of fertilization, the development of testes or ovaries in the bipotential early gonads takes place during embryogenesis. During development, sex determination depends upon very few critical genes. When one of these key genes functions inappropriately, sex reversal may happen. Consequently, an individual's sex phenotype may not necessarily be consistent with the sex chromosomes that are present...
January 13, 2017: Asian Journal of Andrology
https://www.readbyqxmd.com/read/28076754/transcriptome-analysis-of-the-potential-roles-of-foxl2-in-chicken-pre-hierarchical-and-pre-ovulatory-granulosa-cells
#19
Jing Wang, Chengcheng Zhao, Jinqiu Li, Yanping Feng, Yanzhang Gong
Forkheadbox L2 (FOXL2) is a transcription factor involved in mammalian ovarian development, especially in granulosa cell differentiation. However, this factor's function in mature chicken ovary is unclear. To explore the function of FOXL2 in chicken granulosa cells, we performed RNA-seq to compare the transcriptomes of pre-hierarchical (phGCs) and pre-ovulatory granulosa cells (poGCs) by FOXL2 overexpression. We observed that focal adhesion might be one of the key pathways activated during the differentiation of granulosa cells, and FOXL2 might be involved in follicle selection by regulating the expression of cytokines and the concentration of cyclic adenosine monophosphate (cAMP)...
January 5, 2017: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
https://www.readbyqxmd.com/read/28045957/normal-levels-of-sox9-expression-in-the-developing-mouse-testis-depend-on-the-tes-tesco-enhancer-but-this-does-not-act-alone
#20
Nitzan Gonen, Alexander Quinn, Helen C O'Neill, Peter Koopman, Robin Lovell-Badge
During mouse sex determination, transient expression of the Y-linked gene Sry up-regulates its direct target gene Sox9, via a 3.2 kb testis specific enhancer of Sox9 (TES), which includes a core 1.4 kb element, TESCO. SOX9 activity leads to differentiation of Sertoli cells, rather than granulosa cells from the bipotential supporting cell precursor lineage. Here, we present functional analysis of TES/TESCO, using CRISPR/Cas9 genome editing in mice. Deletion of TESCO or TES reduced Sox9 expression levels in XY fetal gonads to 60 or 45% respectively relative to wild type gonads, and reduced expression of the SOX9 target Amh...
January 2017: PLoS Genetics
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