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Z Merhi, E Buyuk, M J Cipolla
STUDY QUESTION: Does vitamin D attenuate the adverse effects of advanced glycation end products (AGEs) on steroidogenesis by human granulosa cells (GCs)? SUMMARY ANSWER: AGEs alter the expression of genes important in steroidogenesis while 1,25-dihydroxyvitamin D3 (vit D3) in vitro attenuates some of the actions of AGEs on steroidogenic gene expression, possibly by downregulating the expression of the pro-inflammatory cell membrane receptor for AGEs (RAGE). WHAT IS KNOWN ALREADY: Vitamin D attenuates the pro-inflammatory effects of AGEs in non-ovarian tissues...
March 12, 2018: Molecular Human Reproduction
Xiaochen Lin, Katie Kei-Hang Chan, Yen-Tsung Huang, Xi Luo, Liming Liang, James Wilson, Adolfo Correa, Daniel Levy, Simin Liu
PURPOSE: Leisure-time physical activity (LTPA) is a well-established modifiable lifestyle determinant for multiple cardio-metabolic outcomes. However, current understanding of the genetic architecture that may determine LTPA remains very limited. Therefore, we aimed to examine the role of genetic factors in affecting LTPA, which has yet to be investigated comprehensively and in-depth. METHODS: We conducted a genome-wide analysis using 1000 Genomes Project imputed data from the Women's Health Initiative (n=11,865), the Jackson Heart Study (n=3,015) and the Framingham Heart Study (n=7,339)...
March 13, 2018: Medicine and Science in Sports and Exercise
Sara Falvo, Gabriella Chieffi Baccaria, Giuseppe Spaziano, Luigi Rosati, Massimo Venditti, Maria Maddalena Di Flore, Alessandra Santillo
The Harderian gland (HG) of the rat (Rattus norvegicus) secretes copious amounts of lipids, such as cholesterol. Here we report a study of the expressions of the StAR protein and key steroidogenic enzymes in the HG of male and female rats. The objective of the present investigation was to ascertain (a) whether the rat HG is involved in steroid production starting with cholesterol, and (b) whether the pattern of gene and protein expressions together with the enzymatic activities display sexual dimorphism. The results demonstrate, for the first time, the expression of StAR gene and protein, and Cyp11a1, Hsd3b1, Hsd17b3, Srd5a1, Srd5a2 and Cyp19a1 genes in the rat HG...
March 10, 2018: Comptes Rendus Biologies
Min Hyun Baek, Jeong Yeol Park, Yangsoon Park, Kyu Rae Kim, Dae Yeon Kim, Dae Shik Suh, Jong Hyeok Kim, Yong Man Kim, Young Tak Kim, Joo Hyun Nam
OBJECTIVE: To investigate the expression of androgen receptor (AR) and its correlation with disease status and survival outcome in uterine leiomyosarcoma with other hormone receptors. METHODS: The medical records and paraffin blocks of 42 patients were reviewed. The immunohistochemical expression of AR, estrogen receptor (ER), progesterone receptor (PR), gonadotropin releasing hormone (GnRH), and cytochrome P450, family 19, subfamily A, polypeptide 1 (CYP19A1) were assessed using tissue microarray...
February 5, 2018: Journal of Gynecologic Oncology
Chenyue Ding, Qinyan Zou, Fuxin Wang, Huihua Wu, Rulei Chen, Jinghuan Lv, Mingfa Ling, Jian Sun, Wei Wang, Hong Li, Boxian Huang
BACKGROUND: Although many reports show that various kinds of stem cells have the ability to recover function in premature ovarian aging, few studies have looked at stem cell treatment of natural ovarian aging (NOA). We designed this experimental study to investigate whether human amniotic mesenchymal stem cells (hAMSCs) retain the ability to restore ovarian function, and how hAMSCs work in this process. METHODS: To build the NOA mouse model, the mice were fed for 12-14 months normally with young fertile female mice as the normal control group (3-5 months old)...
March 9, 2018: Stem Cell Research & Therapy
Rafal P Piprek, Milena Damulewicz, Malgorzata Kloc, Jacek Z Kubiak
Development of the gonads is a complex process, which starts with a period of undifferentiated, bipotential gonads. During this period the expression of sex-determining genes is initiated. Sex determination is a process triggering differentiation of the gonads into the testis or ovary. Sex determination period is followed by sexual differentiation, i.e. appearance of the first testis- and ovary-specific features. In Xenopus laevis W-linked DM-domain gene (DM-W) had been described as a master determinant of the gonadal female sex...
March 2, 2018: Differentiation; Research in Biological Diversity
Maria Wielsøe, Hans Eiberg, Mandana Ghisari, Peder Kern, Ole Lind, Eva Cecilie Bonefeld-Jørgensen
The present study investigated the effects of single nucleotide polymorphisms (SNPs) in xenobiotic and steroid hormone-metabolizing genes in relation to breast cancer risk and explored possible effect modifications on persistent organic pollutants (POPs) and breast cancer associations. The study also assessed effects of Greenlandic BRCA1 founder mutations. Greenlandic Inuit women (77 cases and 84 controls) were included. We determined two founder mutations in BRCA1: Cys39Gly (rs80357164) and 4684delCC, and five SNPs in xenobiotic and oestrogen-metabolizing genes: CYP17A1 -34T>C (rs743572), CYP19A1 *19C>T (rs10046), CYP1A1 Ile462Val (rs1048943), CYP1B Leu432Val (rs1056836) and COMT Val158Met (rs4680)...
March 6, 2018: Basic & Clinical Pharmacology & Toxicology
Chan Jin Park, Heehyen Kim, Jooyoung Jin, Radwa Barakat, Po-Ching Lin, Jeong Moon Choi, CheMyong Jay Ko
17β-estradiol is synthesized primarily in the gonads of both sexes and regulates the development and function of reproductive organs. Lately, we discovered that intestinal lymphocyte homeostasis is regulated by estradiol synthesized de novo in the endothelial cells of high endothelial venule of mesenteric lymph node and Peyer's patches in mice. This finding prompted us to hypothesize that the high endothelial venule of intestinal lymphoid tissues is the site of estradiol synthesis across the species. In this study, we determined if estradiol is synthesized in the porcine intestinal lymphoid tissues using adolescent piglets...
February 27, 2018: Journal of Veterinary Science
Andrée-Anne Hudon Thibeault, Cathy Vaillancourt, J Thomas Sanderson
Estrogen production by the human villous trophoblast is dependent on the biosynthetic enzyme aromatase (CYP19; CYP19A1) and is crucial for successful placental development and pregnancy outcome. Using villous cytotrophoblast cells (vCTs) freshly isolated from normal term placenta, we characterized the promoter-specific expression of CYP19A1 mRNA (derived from promoters I.1, I.4, I.8 or total transcript) and aromatase activity during villous trophoblast syncytialization. CYP19A1 mRNA levels and aromatase activity in vCTs reached a maximum after about 48 h of culture...
February 20, 2018: Biochimie
Benjamin H Mullin, Kun Zhu, Jiake Xu, Suzanne J Brown, Shelby Mullin, Jennifer Tickner, Nathan J Pavlos, Frank Dudbridge, John P Walsh, Scott G Wilson
Osteoporosis is a complex disease with a strong genetic component. Genome-wide association studies (GWAS) have been very successful at identifying common genetic variants associated with bone parameters. A recently published study documented the results of the largest GWAS for bone mineral density (BMD) performed to date (n = 142,487), identifying 307 conditionally independent single-nucleotide polymorphisms (SNPs) as associated with estimated BMD (eBMD) at the genome-wide significance level. The vast majority of these variants are non-coding SNPs...
February 23, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Anja Baufeld, Jens Vanselow
BACKGROUND: The LH-induced folliculo-luteal transformation is connected with alterations of the gene expression profile in cells of the granulosa layer. It has been described that hypoxic conditions occur during luteinization, thus favoring the formation of L-lactate within the follicle. Despite being a product of anaerobic respiration, L-lactate has been shown to act as a signaling molecule affecting gene expression in neuronal cells. During the present study, we tested the hypothesis that L-lactate may influence differentiation of follicular granulosa cells (GC)...
February 20, 2018: Reproductive Biology and Endocrinology: RB&E
Dragana Samardzija Nenadov, Kristina Pogrmic-Majkic, Svetlana Fa, Bojana Stanic, Aleksandra Tubic, Nebojsa Andric
Humans are exposed not only to single endocrine disruptors, but also to chemical mixtures that can adversely affect their reproductive health. Steroidogenesis in reproductive tissues is emerging as the key target of endocrine disruptor action. Here, we analyzed the effect of environmental chemical mixtures with estrogenic activity on steroidogenic processes in immature rat granulosa cells and whether the observed steroidogenic effects were mediated through estrogen receptors. Extracts from untreated wastewater were prepared by solid-phase extraction and silica gel fractionation...
February 13, 2018: Journal of Applied Toxicology: JAT
Alvaro García-Guerra, Aurea M O Canavessi, Pedro L J Monteiro Jr, Megan A Mezera, Roberto Sartori, Brian W Kirkpatrick, Milo C Wiltbank
The acquisition of dominance and ovulatory capacity was evaluated in follicles from cows that were carriers or half-sibling non-carriers of the Trio allele. Follicle size at acquisition of follicular dominance was determined by evaluating whether follicles ovulate after GnRH challenge (ovulatory capacity-experiment 1) and by determination of intra-follicular concentrations of estradiol and free IGF1 and relative mRNA expression of CYP19A1, LHCGR, and PAPPA in granulosa cells from follicles of different sizes (experiment 2)...
February 7, 2018: Biology of Reproduction
Xiuying Jia, Zhengquan Liu, Xiangjun Lu, Juan Tang, Yingzhu Wu, Qiongxia Du, Jianbo He, Xinyun Zhang, Jinxiao Jiang, Wenli Liu, Yuqing Zheng, Ying Ding, Weiqin Zhu, Hangjun Zhang
Microcystin-leucine-arginine (MCLR) is the most popular and toxic variant among microcystins, which can cause severe reproductive toxicity to animals. However, the mechanisms of reproductive toxicity induced by MCLR in amphibians are still not entirely clear. In the current study, toxicity mechanisms of MCLR on the reproductive system of male Rana nigromaculata followed by low concentration (0, 0.1, 1, and 10 μg/L) and short-term (0, 7, and 14 days) MCLR exposure were shown. It was observed that MCLR could be bioaccumulated in the testes of male frogs, and the theoretical bioaccumulation factor values were 0...
February 1, 2018: Environmental Pollution
Lia A Bernardi, Matthew T Dyson, Hideki Tokunaga, Christia Sison, Muge Oral, Jared C Robins, Serdar E Bulun
Endometriotic stromal cells synthesize estradiol via the steroidogenic pathway. Nuclear receptor subfamily 5, group A, member 1 (NR5A1) is critical, but alone not sufficient, in activating this cascade that involves at least 5 genes. To evaluate whether another transcription factor is required for the activation of this pathway, we examined whether GATA Binding Protein 6 (GATA6) can transform a normal endometrial stromal cell (NoEM) into an endometriotic-like cell by conferring an estrogen-producing phenotype...
January 1, 2018: Reproductive Sciences
Yu Gu, Wenbin Xu, Bole Zhuang, Wei Fu
Irregular expression of cytochrome P450 family 19 subfamily A member 1 (CYP19A1) is involved in the development of polycystic ovary syndrome (PCOS). Activation of the cAMP/protein kinase A (PKA)/cAMP response element-binding protein (CREB) pathway plays a crucial role in FSH regulation of CYP19A1 in human ovarian granulosa cells. A-Kinase anchor protein 95 (AKAP95) is known to confine PKA to the nucleus. However, it is unclear whether anchoring PKA to the nucleus is essential for the induction of CYP19A1 by FSH in human ovarian granulosa cells...
February 5, 2018: Reproduction, Fertility, and Development
Jiying Liu, Xinyu Li, Yong Yao, Qiqi Li, Zenxiang Pan, Qifa Li
miR-1275 is one of the microRNAs (miRNAs) that are differentially expressed during follicular atresia in pig ovaries, as identified by a miRNA microarray assay in our previous study. However, its functions in follicular atresia remain unknown. In this study, we showed that miR-1275 promoted early apoptosis of porcine granulosa cells (pGCs) and the initiation of follicular atresia and inhibited E2 release and mRNA and protein expression of CYP19A1, the key gene in E2 production. Bioinformatics and luciferase reporter assays revealed that LRH-1, not CYP19A1, is a direct functional target of miR-1275...
January 26, 2018: Biochimica et Biophysica Acta
Neslihan Coban, Aysem Kaya, Aycan Fahri Erkan, Filiz Guclu-Geyik, Berkay Ekici, Evin Ademoglu, Irem Yagmur Diker, Gunay Can, Nihan Erginel-Unaltuna
No abstract text is available yet for this article.
August 2017: Atherosclerosis
Andrea Friesenhengst, Tamara Pribitzer-Winner, Heidi Miedl, Katharina Pröstling, Martin Schreiber
Genetic variants in CYP19A1, the gene encoding aromatase, have been reported to be associated with circulating estrogen concentrations, a key risk factor for breast cancer. The mechanism underlying this association is still unclear; it has been suggested that some of these variants may alter the expression and/or activity of aromatase. Here we analyzed the expression of intra-tumoral CYP19A1 messenger RNA (mRNA) and the genotypes of rs10046, a well-characterized single nucleotide polymorphism in CYP19A1, in 138 breast cancer patients and 15 breast cancer cell lines...
January 23, 2018: Hormones & Cancer
Giovanna C Cavalcante, Marcos At Amador, André M Ribeiro Dos Santos, Darlen C Carvalho, Roberta B Andrade, Esdras Eb Pereira, Marianne R Fernandes, Danielle F Costa, Ney Pc Santos, Paulo P Assumpção, Ândrea Ribeiro Dos Santos, Sidney Santos
AIM: To evaluate the relation between 12 polymorphisms and the development of gastric cancer (GC) and colorectal cancer (CRC). METHODS: In this study, we included 125 individuals with GC diagnosis, 66 individuals with CRC diagnosis and 475 cancer-free individuals. All participants resided in the North region of Brazil and authorized the use of their samples. The 12 polymorphisms (in CASP8, CYP2E1, CYP19A1, IL1A, IL4, MDM2, NFKB1, PAR1, TP53, TYMS, UGT1A1 and XRCC1 genes) were genotyped in a single PCR for each individual, followed by fragment analysis...
December 28, 2017: World Journal of Gastroenterology: WJG
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