{"title":"Physiology of Cellular Prion Proteins in Reproduction.","authors":"Željko M Svedružić, Chongsuk Ryou, Donchan Choi, Sung-Ho Lee, Yong-Pil Cheon","doi":"10.12717/DR.2024.28.2.29","DOIUrl":"10.12717/DR.2024.28.2.29","url":null,"abstract":"<p><p>Cellular prion protein (PrP<sup>C</sup>) encoded at <i>Prnp</i> gene is well-known to form a misfolded isoform, termed scrapie PrP (PrP<sup>SC</sup>) that cause transmissible degenerative diseases in central nervous system. The physiological role of PrP<sup>C</sup> has been proposed by many studies, showing that PrP<sup>C</sup> interacts with various intracellular, membrane, and extracellular molecules including mitochondrial inner membrane as a scaffold. PrP<sup>C</sup> is expressed in most cell types including reproductive organs. Numerous studies using PrP<sup>C</sup> knockout rodent models found no obvious phenotypic changes, in particular the clear phenotypes in development and reproduction have not demonstrated in these knockout models. However, various roles of PrP<sup>C</sup> have been evaluated at the cellular levels. In this review, we summarized the known roles of PrP<sup>C</sup> in various cell types and tissues with a special emphasis on those involved in reproduction.</p>","PeriodicalId":72791,"journal":{"name":"Development & reproduction","volume":"28 2","pages":"29-36"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11268893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seung-Yul Lee, Tae Jeong Oh, Sungwhan An, Seung-Hoon Lee
{"title":"Overexpression of Hypermethylated Homeobox A11 (HOXA11) Inhibits Tumor Cell Growth and Induces Apoptosis in Cervical Cancer.","authors":"Seung-Yul Lee, Tae Jeong Oh, Sungwhan An, Seung-Hoon Lee","doi":"10.12717/DR.2024.28.2.37","DOIUrl":"10.12717/DR.2024.28.2.37","url":null,"abstract":"<p><p>This study aimed to elucidate the potential of Homeobox A11 (HOXA11) as a therapeutic target and a diagnostic methylation marker for cervical cancer. Gene expression analysis using cDNA microarray in cervical cancer cell lines revealed significantly reduced expression of the HOXA11 gene. Subsequent investigation of HOXA11 promoter methylation in samples from normal individuals and invasive cervical cancer patients showed over 53.2% higher methylation in cancer scrapes compared to normal scrapes. Furthermore, overexpression of HOXA11, which is downregulated in cervical cancer, strongly suppressed cell growth in cervical cancer cell lines, HeLa and HT3. Additionally, we performed transferase dUTP nick end labeling assay and confirmed that the inhibition of cervical cancer cell proliferation occurred via apoptosis. Mechanistically, overexpression of HOXA11 led to mitochondrial apoptosis characterized by PARP cleavage due to increased c-Myc and enhanced cytochrome C secretion into the cytoplasm. These findings suggest that HOXA11 could potentially serve as a methylation marker for diagnosing cervical cancer and as a novel therapeutic target for its treatment.</p>","PeriodicalId":72791,"journal":{"name":"Development & reproduction","volume":"28 2","pages":"37-45"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11268892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Soeun Moon, Bokyeong Yun, Minju Lee, Eunji Seok, Jinah Ha, Hyunwon Yang
{"title":"Gonadotropins Regulate the mRNA Expression of Gonadotropin-Releasing Hormone and Its Receptors in the Mouse Ovary and Uterus.","authors":"Soeun Moon, Bokyeong Yun, Minju Lee, Eunji Seok, Jinah Ha, Hyunwon Yang","doi":"10.12717/DR.2024.28.1.1","DOIUrl":"https://doi.org/10.12717/DR.2024.28.1.1","url":null,"abstract":"","PeriodicalId":72791,"journal":{"name":"Development & reproduction","volume":"28 1","pages":"1-12"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11034991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140860769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Si-On You, Han-Seo Yoon, Hye-Soo Kim, Jin-Soo Park, Sung-Ho Lee
{"title":"Temporal Changes in the Local Expression of Central Hormone-Regulating Factors in Rat Testis.","authors":"Si-On You, Han-Seo Yoon, Hye-Soo Kim, Jin-Soo Park, Sung-Ho Lee","doi":"10.12717/DR.2024.28.1.21","DOIUrl":"https://doi.org/10.12717/DR.2024.28.1.21","url":null,"abstract":"","PeriodicalId":72791,"journal":{"name":"Development & reproduction","volume":"28 1","pages":"21-28"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11034993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Partial Lipectomy of the Epididymal Fat Alters Expression of the Steroidogenic Enzymes in the Mouse Testis at Different Postnatal Ages.","authors":"Yong-Seung Lee, Ki-Ho Lee","doi":"10.12717/DR.2023.27.4.175","DOIUrl":"10.12717/DR.2023.27.4.175","url":null,"abstract":"<p><p>The epididymal fat is a type of gonadal adipose tissue, which is localized closely to the testis. Even though it has been suggested that the epididymal fat is necessary for maintenance of spermatogenesis in the testis, the influence of epididymal fat on expression of testicular steroidogenic enzymes has not been examined. In the present research, expressional changes of steroidogenic enzymes in the mouse testis after 2 weeks of the surgical partial lipectomy of epididymal fat at different postnatal ages were determined by real-time polymerase chain reaction analysis. The transcript levels of all molecules at 2 months of postnatal age were significantly increased by the lipectomy of epididymal fat. However, the lipectomy at 5 months of postnatal age resulted in decreases of expression levels of all molecules examined in the testis. Except a reduced transcript level of hydroxysteroid 17-beta dehydrogenase 3, there were no significant changes of expression levels of other steroidogenic enzymes by the lipectomy at 8 months of postnatal age. At 12 months of postnatal age, the lipectomy caused a significant increase of transcript level of steroidogenic acute regulatory protein and a significant decrease of transcript level of hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1, without any expressional change of cytochrome P450 side chain cleavage, hydroxysteroid 17-beta dehydrogenase 3, and hydroxysteroid 17-beta dehydrogenase 3 in the testis. These findings suggest that the substances derived from epididymal fat could differentially influence on expression of steroidogenic enzymes in the testis during postnatal period.</p>","PeriodicalId":72791,"journal":{"name":"Development & reproduction","volume":"27 4","pages":"175-183"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10824564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139643537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of Nonylphenol on the Secretion of Catecholamines and Adrenocortical Hormones from Short-Term Incubated Rat Adrenal Glands.","authors":"Hee-Su Kim, Yong-Pil Cheon, Sung-Ho Lee","doi":"10.12717/DR.2023.27.4.213","DOIUrl":"10.12717/DR.2023.27.4.213","url":null,"abstract":"<p><p>Previously, we showed that a chronic-low-dose nonylphenol (NP) exposure resulted in histological changes with sexually dimorphic pattern in rat adrenal glands. We hypothesized that such structural changes are closely related to the hormonal secretory patterns. To test this hypothesis, we developed the short-term adrenal incubation method, and measured the levels of catecholamines and cortical steroids using the high-performance liquid chromatography with electrochemical detection (HPLC-ECD) and specific enzyme-linked immunosorbent assay, respectively. The norepinephrine (NE) levels in media from NP-treated female adrenal, except 100 pM NP, were significantly increased [control (CTL) vs 1 nM NP, <i>p</i><0.001; vs 10 nM NP, <i>p</i><0.05; vs 100 nM NP, <i>p</i><0.001; vs 1 μM NP, <i>p</i><0.01]. The NE secretion from male adrenal was higher when treated with 100 nM and 1 μM NP (CTL vs 100 nM NP, <i>p</i><0.05; vs 1 μM NP, <i>p</i><0.05, respectively). The aldosterone level in the female adrenal media treated with 100 pM NP was significantly decreased, on the other hand, that of media treated with 10 nM NP was significantly increased (CTL vs 100 pM NP, <i>p</i><0.05; vs 10 nM NP, <i>p</i><0.01). In male adrenal media, the aldosterone levels of 10 nM, 100 nM and 1 μM NP-treated media were significantly declined (CTL vs 10 nM NP, <i>p</i><0.001; vs 100 nM NP, <i>p</i><0.001; vs 1 μM NP, <i>p</i><0.001). These results showed the NP treatment altered secretory pattern of aldosterone from adrenals of both sexes, showing sexual dimorphism. It may be helpful for understanding possible adrenal pathophysiology, and endocrine disrupting chemicals-related sexually dimorphic phenomena in adrenals.</p>","PeriodicalId":72791,"journal":{"name":"Development & reproduction","volume":"27 4","pages":"213-220"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10824570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139643533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ji-Eun Park, Seung Gee Lee, Seung-Jin Lee, Wook-Joon Yu, Jong-Min Kim
{"title":"Downregulation of the Expression of Steroidogenic Acute Regulatory Protein and Aromatase in Steroidogenic KGN Human Granulosa Cells after Exposure to Bisphenol A.","authors":"Ji-Eun Park, Seung Gee Lee, Seung-Jin Lee, Wook-Joon Yu, Jong-Min Kim","doi":"10.12717/DR.2023.27.4.185","DOIUrl":"10.12717/DR.2023.27.4.185","url":null,"abstract":"<p><p>Although increasing evidence of cause-and-effect relationship between BPA exposure and female reproductive disorders have been suggested through many studies, the precise biochemical and molecular mechanism(s) by which BPA interferes with steroidogenesis in the ovarian cells still remain unclear. Therefore, the purpose of this study was to discover the steroidogenic biomarker(s) associated with BPA treatment in human granulosa cell line, KGN. In this study, our results obtained via the analysis of steroidogenesis-related protein expression in KGN cells using quantitative polymerase chain reaction (qPCR) and western blot analyses revealed that the expression levels of steroidogenic acute regulatory (StAR) and aromatase decreased considerably and gradually after BPA treatment in a dose-dependent manner under BPA treatment. Further, remarkable decreases in their expression levels at the cellular levels were also confirmed via immunocytochemistry, and subsequent StAR and aromatase mRNA expression levels showed profiles similar to those observed for their proteins, i.e., both StAR and aromatase mRNA expression levels were significantly decreased under BPA treatment at concentrations ≥0.1 μM. We observed that follicle stimulating hormone upregulated StAR and aromatase protein expression levels; however, this effect was suppressed in the presence of BPA. Regarding the steroidogenic effects of BPA on KGN cells, controversies remain regarding the ultimate outcomes. Nevertheless, we believe that the results here presented imply that KGN cells have a good cellular and steroidogenic machinery for evaluating endocrine disruption. Therefore, StAR and aromatase could be stable and sensitive biomarkers in KGN cells for the cellular screening of the potential risk posed by exogenous and environmental chemicals to female reproductive (endocrine) function.</p>","PeriodicalId":72791,"journal":{"name":"Development & reproduction","volume":"27 4","pages":"185-193"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10824569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139643532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seung Gee Lee, Ji-Eun Park, Yong-Pil Cheon, Jong-Min Kim
{"title":"Gestational Exposure to Bisphenol A Causes DNA Hypomethylation and the Upregulation of Progesterone Receptor Expression in the Uterus in Adult Female Offspring Rats.","authors":"Seung Gee Lee, Ji-Eun Park, Yong-Pil Cheon, Jong-Min Kim","doi":"10.12717/DR.2023.27.4.195","DOIUrl":"10.12717/DR.2023.27.4.195","url":null,"abstract":"<p><p>Exposure to environmental chemicals, including endocrine-disrupting chemicals, during the gestational period can have profound adverse effects on several organs in offspring. Bisphenol A (BPA) can infiltrate the human body through food and drinks, and its metabolites can cross both the placental and the blood-brain barriers. In this study, we investigate the effect of gestational exposure to BPA on epigenetic, biochemical, and histological modifications in the uterine tissues of F1 adult offspring rats. Pregnant rats were exposed to BPA from gestational day 8-15, and changes in global DNA methylation in uterine tissues obtained from adult offspring born to the exposed mothers were analyzed. Global DNA methylation analysis revealed that gestational exposure to BPA resulted in DNA hypomethylation in the uterus. Progesterone receptor (PR) protein expression in uterine tissues was monitored using western blot analysis, which revealed that the PR protein content was considerably higher in all BPA-exposed groups than in the control. Immunohistochemical examination for the PR revealed that intense PR-positive cells were more frequently observed in the BPA-exposed group than in the control group. To date, the evidence that the upregulation of PRs observed in the present study was caused by the non-methylation of specific PR promoter regions is lacking. Conclusively, these results indicate that exposure to BPA during gestation induces epigenetic alterations in the uteri of adult female offspring. We speculate that the global DNA hypomethylation and upregulation of the PR observed simultaneously in this study might be associated with the uterus.</p>","PeriodicalId":72791,"journal":{"name":"Development & reproduction","volume":"27 4","pages":"195-203"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10824565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139643535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ji Hye Jung, Sanghoon Jeon, Heabin Kim, Seung-Hyun Jung
{"title":"Generation of <i>ints14</i> Knockout Zebrafish using CRISPR/Cas9 for the Study of Development and Disease Mechanisms.","authors":"Ji Hye Jung, Sanghoon Jeon, Heabin Kim, Seung-Hyun Jung","doi":"10.12717/DR.2023.27.4.205","DOIUrl":"10.12717/DR.2023.27.4.205","url":null,"abstract":"<p><p>INTS14/VWA9, a component of the integrator complex subunits, plays a pivotal role in regulating the fate of numerous nascent RNAs transcribed by RNA polymerase II, particularly in the biogenesis of small nuclear RNAs and enhancer RNAs. Despite its significance, a comprehensive mutation model for developmental research has been lacking. To address this gap, we aimed to investigate the expression patterns of <i>INTS14</i> during zebrafish embryonic development. We generated <i>ints14</i> mutant strains using the CRISPR/Cas9 system. We validated the gRNA activity by co-injecting Cas9 protein and a single guide RNA into fertilized zebrafish eggs, subsequently confirming the presence of a 6- or 9-bp deletion in the <i>ints14</i> gene. In addition, we examined the two mutant alleles through PCR analysis, T7E1 assay, TA-cloning, and sequencing. For the first time, we used the CRISPR/Cas9 system to create a model in which some sequences of the <i>ints14</i> gene were removed. This breakthrough opens new avenues for in-depth exploration of the role of <i>ints14</i> in animal diseases. The mutant strains generated in this study can provide a valuable resource for further investigations into the specific consequences of <i>ints14</i> gene deletion during zebrafish development. This research establishes a foundation for future studies exploring the molecular mechanisms underlying the functions of <i>ints14</i>, its interactions with other genes or proteins, and its broader implications for biological processes.</p>","PeriodicalId":72791,"journal":{"name":"Development & reproduction","volume":"27 4","pages":"205-211"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10824568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139643534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}