Abstract:
:We have previously demonstrated that the reduced form of vitamin C (l-ascorbic acid, AA) is able to induce the production of both steroid and peptide hormones in human choriocarcinoma cells. Here, we attempted to investigate the role and underlying mechanism of the oxidized form of vitamin C, dehydroascorbic acid (DHA), in steroidogenesis in primary human cytotrophoblasts and human choriocarcinoma cells. Messenger RNA and protein levels of steroidogenic enzymes including P450 cholesterol side-chain cleavage enzyme (P450scc), 3β-hydroxysteroid dehydrogenase type 1 (3β-HSD1), 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) and aromatase were examined by quantitative RT-PCR and western blots, respectively. Progesterone (P4) and estradiol (E2) levels were determined by enzyme immunoassays. Knockdown of c-Jun was achieved by lentivirus-mediated shRNA, and signaling pathways implicated in DHA-induced steroidogenesis were examined by western blots and dual-luciferase assays. DHA dose-dependently induced the expression of steroidogenic enzymes including 3β-HSD1, 17β-HSD1 and aromatase at both mRNA and protein levels, and subsequently increased the production of E2 but not P4. These effects were synergized by diethylmaleate, a glutathione-depleting compound, and α-tocopherol, a reducing agent, but robustly attenuated by inhibition of DHA transportation by phloretin or 2-deoxy-d-glucose. DHA time-dependently inhibited JNK and c-Jun phosphorylation, and dose-dependently reduced AP1 reporter activity. JNK signaling pathway-specific inhibitor SP600125 and c-Jun shRNA both significantly increased the expression of steroidogenic enzymes and E2 production regardless of the presence or absence of DHA. These findings suggest that DHA is able to induce steroidogenesis through inhibition of JNK/c-Jun/AP1 signaling, and may therefore play indispensable roles in pregnancy maintenance.
journal_name
Mol Hum Reprodjournal_title
Molecular human reproductionauthors
Wang Y,Tang C,Wu M,Pan Y,Ruan H,Chen L,Yao H,Zhu H,Wu Xdoi
10.1093/molehr/gau036subject
Has Abstractpub_date
2014-08-01 00:00:00pages
799-809issue
8eissn
1360-9947issn
1460-2407pii
molehr/gau036journal_volume
20pub_type
杂志文章abstract::We investigated the expression of methyl transferase G9a and methylated histone H3-K9 in fresh human decidual/endometrial tissue of 12 normal early pregnancies and 15 unexplained recurrent spontaneous abortions (URSA). The samples were obtained through dilatation and curettage and collected as per strict inclusion-exc...
journal_title:Molecular human reproduction
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journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/2.4.265
更新日期:1996-04-01 00:00:00
abstract::The use of interphase fluorescent in situ hybridization (FISH) has shown that a large number of human embryos exhibit chromosomal abnormalities in vitro. The most common abnormality is mosaicism which is seen in up to 50% of preimplantation embryos at all stages of development. In this study, comparative genomic hybri...
journal_title:Molecular human reproduction
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doi:10.1093/molehr/gam087
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journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gam079
更新日期:2008-01-01 00:00:00
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pub_type: 杂志文章
doi:10.1093/molehr/6.12.1079
更新日期:2000-12-01 00:00:00
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journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/3.5.445
更新日期:1997-05-01 00:00:00
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journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gah120
更新日期:2004-12-01 00:00:00
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pub_type: 杂志文章
doi:10.1093/molehr/gap045
更新日期:2009-10-01 00:00:00
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journal_title:Molecular human reproduction
pub_type: 杂志文章,评审
doi:10.1093/molehr/gag064
更新日期:2003-08-01 00:00:00
abstract::A number of placental cytokines participate in the feto-maternal defence mechanism. Monocyte chemotactic and activating factor (MCAF) is one of these chemokines. We investigated the pattern of placental MCAF production, the localization of MCAF-producing cells in the placenta, and alterations in its expression in chor...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/4.4.393
更新日期:1998-04-01 00:00:00
abstract::Several lines of evidence indicate that mammalian fertilization is initiated via a binding process that is dependent upon the recognition of oligosaccharide sequences associated with zona pellucida (ZP) glycoproteins. Here, specific chemical and enzymatic methods were employed to modify human ZP and to test their effe...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/4.4.318
更新日期:1998-04-01 00:00:00
abstract::Prostaglandins (PGs) are important factors in the physiology of human parturition and the control of uterine contractility. We have characterized the expression of 15 genes from all stages of the PG pathway in human pregnant and non-pregnant (NP) myometrium and in other uterine tissues at delivery, and the results sho...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gaq057
更新日期:2011-01-01 00:00:00
abstract::Oxidative damage by reactive oxygen species (ROS) is a major cause of sperm dysfunction. Excessive ROS generation reduces fertilization and enhances DNA damage of spermatozoa. Interaction between spermatozoa and oviductal epithelial cells improves the fertilizing ability of and reduces chromatin damage in spermatozoa....
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gav015
更新日期:2015-06-01 00:00:00
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journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/3.1.69
更新日期:1997-01-01 00:00:00
abstract::The major regulators of endometrial function are oestrogen and progesterone, which act through binding their nuclear receptors and by activating transcription of their target genes. Interactions between steroid receptors and transcription proteins, e.g. c-JUN/AP-1, can modulate steroid action at the transcriptional le...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/4.12.1110
更新日期:1998-12-01 00:00:00
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journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/4.11.1071
更新日期:1998-11-01 00:00:00
abstract::Cystic fibrosis (CF) is usually considered a rare disease in the Indian population. Two studies have reported on the frequency of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in Indian males with congenital absence of the vas deferens (CAVD), however, data on the spectrum of CFTR gene muta...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gau047
更新日期:2014-09-01 00:00:00
abstract::Human mitochondrial DNA (mtDNA) rearrangements, including more than 150 deletions and insertions, accumulate with age and are responsible for certain neuromuscular diseases. Human oocytes, arrested for up to 50 years, may express certain mtDNA rearrangements possibly affecting function. Investigations have previously ...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/5.10.927
更新日期:1999-10-01 00:00:00
abstract:STUDY QUESTION:Does dynamin regulate human sperm acrosomal exocytosis? SUMMARY ANSWER:Our studies of dynamin localization and function have implicated this family of mechanoenzymes in the regulation of progesterone-induced acrosomal exocytosis in human spermatozoa. WHAT IS KNOWN ALREADY:Completion of an acrosome reac...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gax044
更新日期:2017-10-01 00:00:00
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journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gap083
更新日期:2010-02-01 00:00:00
abstract::The human endometrium is a dynamic tissue, which undergoes extensive tissue remodelling during the menstrual cycle. Due to their involvement in such processes, several well-characterized matrix metalloproteinases (MMP) have previously been studied in the endometrium. MMP-26 is a newly described matrilysin. We studied ...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gag039
更新日期:2003-05-01 00:00:00
abstract::Fatty acid amide hydrolase (FAAH) is involved in embryo development and implantation. Sex hormones down-modulate FAAH activity in the mouse uterus. However, the regulation of the FAAH gene in the uterus is unknown. Our results showed that FAAH mRNA is localized to uterine epithelial cells and circular myometrium durin...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/8.7.651
更新日期:2002-07-01 00:00:00
abstract::The human endometrium is a cyclically regenerating organ under the influence of ovarian steroid hormones. Disturbances in this highly coordinated regulation of endometrial proliferation and differentiation may result in infertility and diseases such as endometriosis and endometrial cancer. Environmental toxins belongi...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gaq081
更新日期:2011-02-01 00:00:00
abstract::Type I inositol 1,4,5-trisphosphate-sensitive receptors (InsP(3)R) are expressed in human oocytes and may be involved in operating the Ca(2+) release triggered by the fertilizing sperm. This study examines the contribution of type I InsP(3)R in operating Ca(2+) release in human oocytes secondary to InsP(3) itself, usi...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/8.10.912
更新日期:2002-10-01 00:00:00
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journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gar010
更新日期:2011-07-01 00:00:00
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journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/3.11.953
更新日期:1997-11-01 00:00:00
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journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gat073
更新日期:2014-02-01 00:00:00
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journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gah172
更新日期:2005-05-01 00:00:00