Developmental and hormonal regulation of ubiquitin-like with plant homeodomain and really interesting new gene finger domains 1 gene expression in ovarian granulosa and theca cells of cattle

Abstract Ubiquitin-like with plant homeodomain and really interesting new gene finger domains 1 (UHRF1) is a multi-domain nuclear protein that plays an important role in epigenetics and tumorigenesis, but its role in normal ovarian follicle development remains unknown. Thus, the present study evaluated if UHRF1 mRNA abundance in bovine follicular cells is developmentally and hormonally regulated, and if changes in UHRF1 are associated with changes in DNA methylation in follicular cells. Abundance of UHRF1 mRNA was greater in granulosa cells (GC) and theca cells (TC) from small (<6 mm) than large (≥8 mm) follicles and was greater in small-follicle GC than TC. In GC and TC, fibroblast growth factor 9 (FGF9) treatment increased (P < 0.05) UHRF1 expression by 2-fold. Also, luteinizing hormone (LH) and insulin-like growth factor 1 (IGF1) increased (P < 0.05) UHRF1 expression in TC by 2-fold, and forskolin (an adenylate cyclase inducer) alone or combined with IGF1 increased (P < 0.05) UHRF1 expression by 3-fold. An E2F transcription factor inhibitor (E2Fi) decreased (P < 0.05) UHRF1 expression by 44% in TC and by 99% in GC. Estradiol, progesterone, and dibutyryl-cAMP decreased (P < 0.05) UHRF1 mRNA abundance in GC. Treatment of GC with follicle-stimulating hormone (FSH) alone had no effect but when combined with IGF1 enhanced the UHRF1 mRNA abundance by 2.7-fold. Beauvericin (a mycotoxin) completely inhibited the FSH plus IGF1-induced UHRF1 expression in small-follicle GC. Treatments that increased UHRF1 mRNA (i.e., FGF9) in GC tended to decrease (by 63%; P < 0.10) global DNA methylation, and those that decreased UHRF1 mRNA (i.e., E2Fi) in GC tended to increase (by 2.4-fold; P < 0.10) global DNA methylation. Collectively, these results suggest that UHRF1 expression in both GC and TC is developmentally and hormonally regulated, and that UHRF1 may play a role in follicular growth and development as well as be involved in ovarian epigenetic processes.

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Hormonal regulation of vascular endothelial growth factor A (VEGFA) gene expression in granulosa and theca cells of cattle1

Journal of Animal Science ◽

10.1093/jas/skz164 ◽

2019 ◽

Vol 97 (7) ◽

pp. 3034-3045 ◽

Cited By ~ 4

Author(s):

Jacqueline A Nichols ◽

Maria Chiara Perego ◽

Luis F Schütz ◽

Amber M Hemple ◽

Leon J Spicer

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Hormonal Regulation ◽

Follicular Development ◽

Mrna Abundance ◽

Vascular Endothelial ◽

Theca Cells ◽

E2f Transcription Factor ◽

E2f Transcription Factors ◽

Endothelial Growth Factor

Abstract Vascular endothelial growth factor A (VEGFA) stimulates angiogenesis and is associated with increased vascularity in ovarian follicles of cattle. The objectives of this study were to investigate the developmental and hormonal regulation of VEGFA expression in ovarian granulosa and theca cells (TC) of cattle. Bovine ovaries were collected from a local slaughterhouse and granulosa cells (GC) and TC were collected from small (SM; 1 to 5 mm) and large (LG; 8 to 20 mm) follicles. Cells were collected fresh or cultured in serum-free medium and treated with various factors that regulate angiogenesis and follicular development. RNA was collected for analysis of VEGFA mRNA abundance via quantitative PCR. In SM-follicle GC (SMGC), prostaglandin E2 (PGE2) and FSH decreased (P < 0.05) VEGFA mRNA abundance by 30 to 46%, whereas in LG-follicle GC (LGGC), PGE2 and FSH were without effect (P > 0.10). In SMGC, dihydrotestosterone (DHT), sonic hedgehog (SHH), and growth differentiation factor-9 (GDF9) decreased (P < 0.05) VEGFA expression by 30 to 40%. Fibroblast growth factor-9 (FGF9) and estradiol (E2) were without effect (P > 0.10) on VEGFA mRNA in both SMGC and LGGC, whereas progesterone increased (P < 0.05) VEGFA mRNA in LGGC but had no effect in LGTC. Bone morphogenetic protein-4 (BMP4), LH, and FGF9 increased (P < 0.05) abundance of VEGFA mRNA by 1.5- to 1.9-fold in LGTC. Insulin-like growth factor-1 (IGF1) was without effect (P > 0.10) on VEGFA mRNA in both TC and GC. An E2F transcription factor inhibitor, HLM0064741 (E2Fi), dramatically (i.e., 8- to 13-fold) stimulated (P < 0.01) the expression of VEGFA mRNA expression in both SMGC and LGTC. Abundance of VEGFA mRNA was greater (P < 0.05) in LGGC and SMGC than in LGTC. Also, SMTC had greater (P < 0.05) abundance of VEGFA mRNA than LGTC. In conclusion, VEGFA mRNA abundance was greater in GC than TC, and VEGFA expression decreased in TC during follicle development. Some treatments either suppressed, stimulated, or had no effect on VEGFA expression depending on the cell type. The inhibition of E2F transcription factors had the greatest stimulatory effect of all treatments evaluated, and thus, E2Fs may play an important role in regulating angiogenesis during follicle growth in cattle.

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Regulation and action of fibroblast growth factor 17 in bovine follicles

Journal of Endocrinology ◽

10.1677/joe-09-0145 ◽

2009 ◽

Vol 202 (3) ◽

pp. 347-353 ◽

Cited By ~ 39

Author(s):

M F Machado ◽

V M Portela ◽

C A Price ◽

I B Costa ◽

P Ripamonte ◽

...

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Granulosa Cells ◽

Cumulus Cells ◽

Mrna Abundance ◽

Fibroblast Growth ◽

Theca Cells ◽

Progesterone Secretion ◽

Igf I

Fibroblast growth factor 17 (FGF17) is a member of the FGF8 subfamily that appears to be relevant to folliculogenesis and oogenesis, as the prototype member FGF8 is an oocyte-derived protein that signals to cumulus cells. FGF8 has structural and receptor-binding similarities to FGF17, whose expression in the ovary has not been reported. In this study, we demonstrate localization of FGF17 protein to the oocyte of preantral follicles, and to the oocyte and granulosa cells of antral follicles. Real-time PCR demonstrated the presence of mRNA in oocytes and, to a lesser extent, in granulosa and theca cells. FGF17 mRNA abundance was low in granulosa and theca cells from healthy follicles and increased significantly in atretic follicles. Addition of FSH or IGF-I to granulosa cells in vitro decreased FGF17 mRNA abundance, and treatment with FGF17 inhibited estradiol and progesterone secretion from granulosa cells in relation to control cultures without these additives. We conclude that FGF17 is a potential mediator of granulosa cell differentiation.

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Effects of paternal folate deficiency on the expression of insulin-like growth factor-2 and global DNA methylation in the fetal brain

Molecular Nutrition & Food Research ◽

10.1002/mnfr.201200558 ◽

2012 ◽

Vol 57 (4) ◽

pp. 671-676 ◽

Cited By ~ 27

Author(s):

Hye Won Kim ◽

Ki Nam Kim ◽

Yun Jung Choi ◽

Namsoo Chang

Keyword(s):

Dna Methylation ◽

Growth Factor ◽

Fetal Brain ◽

Folate Deficiency ◽

Global Dna Methylation ◽

Insulin Like Growth Factor

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Global DNA Methylation is influenced by smoking behavior

Pharmacopsychiatry ◽

10.1055/s-2007-991871 ◽

2007 ◽

Vol 40 (05) ◽

Author(s):

MAN Muschler ◽

T Hillemacher ◽

H Frieling ◽

S Moskau ◽

A Semmler ◽

...

Keyword(s):

Dna Methylation ◽

Smoking Behavior ◽

Global Dna Methylation

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Faculty Opinions recommendation of Tissue-specific imprinting of the mouse insulin-like growth factor II receptor gene correlates with differential allele-specific DNA methylation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718529393.793498524 ◽

2014 ◽

Author(s):

Christopher Gregg

Keyword(s):

Dna Methylation ◽

Growth Factor ◽

Receptor Gene ◽

Insulin Like Growth Factor ◽

Tissue Specific ◽

Factor Ii ◽

Allele Specific

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Hormonal Regulation of Insulin-Like Growth Factor I Secretion by Bovine Adrenal Cells

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)83509-8 ◽

1989 ◽

Vol 264 (12) ◽

pp. 6858-6862

Author(s):

A Penhoat ◽

D Naville ◽

C Jaillard ◽

P G Chatelain ◽

J M Saez

Keyword(s):

Growth Factor ◽

Hormonal Regulation ◽

Insulin Like Growth Factor ◽

Adrenal Cells ◽

Factor I ◽

Growth Factor I

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Oxidative damage, inflammation, genotoxic effect, and global DNA methylation caused by inhalation of formaldehyde and the purpose of melatonin

Toxicology Research ◽

10.1093/toxres/tfaa079 ◽

2020 ◽

Vol 9 (6) ◽

pp. 778-789

Author(s):

Letícia Bernardini ◽

Eduardo Barbosa ◽

Mariele Feiffer Charão ◽

Gabriela Goethel ◽

Diana Muller ◽

...

Keyword(s):

Dna Methylation ◽

Bone Marrow ◽

Oxidative Damage ◽

Bronchoalveolar Lavage ◽

Bone Marrow Cells ◽

Histological Study ◽

Global Dna Methylation ◽

Protective Effects ◽

Global Methylation ◽

Protein Thiols

Abstract Formaldehyde (FA) exposure has been proven to increase the risk of asthma and cancer. This study aimed to evaluate for 28 days the FA inhalation effects on oxidative stress, inflammation process, genotoxicity, and global DNA methylation in mice as well as to investigate the potential protective effects of melatonin. For that, analyses were performed on lung, liver and kidney tissues, blood, and bone marrow. Bronchoalveolar lavage was used to measure inflammatory parameters. Lipid peroxidation (TBARS), protein carbonyl (PCO), non-protein thiols (NPSH), catalase activity (CAT), comet assay, micronuclei (MN), and global methylation were determined. The exposure to 5-ppm FA resulted in oxidative damage to the lung, presenting a significant increase in TBARS and NO levels and a decrease in NPSH levels, besides an increase in inflammatory cells recruited for bronchoalveolar lavage. Likewise, in the liver tissue, the exposure to 5-ppm FA increased TBARS and PCO levels and decreased NPSH levels. In addition, FA significantly induced DNA damage, evidenced by the increase of % tail moment and MN frequency. The pretreatment of mice exposed to FA applying melatonin improved inflammatory and oxidative damage in lung and liver tissues and attenuated MN formation in bone marrow cells. The pulmonary histological study reinforced the results observed in biochemical parameters, demonstrating the potential beneficial role of melatonin. Therefore, our results demonstrated that FA exposure with repeated doses might induce oxidative damage, inflammatory, and genotoxic effects, and melatonin minimized the toxic effects caused by FA inhalation in mice.

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Thymoquinone Is a Multitarget Single Epidrug That Inhibits the UHRF1 Protein Complex

Genes ◽

10.3390/genes12050622 ◽

2021 ◽

Vol 12 (5) ◽

pp. 622

Author(s):

Omeima Abdullah ◽

Ziad Omran ◽

Salman Hosawi ◽

Ali Hamiche ◽

Christian Bronner ◽

...

Keyword(s):

Dna Methylation ◽

Dna Methyltransferase ◽

Ring Finger ◽

Macromolecular Complex ◽

Anticancer Activities ◽

Histone Deacetylase 1 ◽

Promoter Dna Methylation ◽

New Gene ◽

Regulatory Effects ◽

Promoter Dna

Silencing of tumor suppressor genes (TSGs) through epigenetic mechanisms, mainly via abnormal promoter DNA methylation, is considered a main mechanism of tumorigenesis. The abnormal DNA methylation profiles are transmitted from the cancer mother cell to the daughter cells through the involvement of a macromolecular complex in which the ubiquitin-like containing plant homeodomain (PHD), and an interesting new gene (RING) finger domains 1 (UHRF1), play the role of conductor. Indeed, UHRF1 interacts with epigenetic writers, such as DNA methyltransferase 1 (DNMT1), histone methyltransferase G9a, erasers like histone deacetylase 1 (HDAC1), and functions as a hub protein. Thus, targeting UHRF1 and/or its partners is a promising strategy for epigenetic cancer therapy. The natural compound thymoquinone (TQ) exhibits anticancer activities by targeting several cellular signaling pathways, including those involving UHRF1. In this review, we highlight TQ as a potential multitarget single epidrug that functions by targeting the UHRF1/DNMT1/HDAC1/G9a complex. We also speculate on the possibility that TQ might specifically target UHRF1, with subsequent regulatory effects on other partners.

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Decreased expression of DNA methyltransferases in the testes of patients with non-obstructive azoospermia leads to changes in global DNA methylation levels

Reproduction Fertility and Development ◽

10.1071/rd18246 ◽

2019 ◽

Vol 31 (8) ◽

pp. 1386 ◽

Cited By ~ 1

Author(s):

Fatma Uysal ◽

Gokhan Akkoyunlu ◽

Saffet Ozturk

Keyword(s):

Dna Methylation ◽

Male Infertility ◽

De Novo ◽

Biological Effects ◽

Testicular Biopsy ◽

Round Spermatid ◽

Dna Methyltransferases ◽

Global Dna Methylation ◽

Obstructive Azoospermia ◽

Spermatogenic Cells

DNA methylation plays key roles in epigenetic regulation during mammalian spermatogenesis. DNA methyltransferases (DNMTs) function in de novo and maintenance methylation processes by adding a methyl group to the fifth carbon atom of the cytosine residues within cytosine–phosphate–guanine (CpG) and non-CpG dinucleotide sites. Azoospermia is one of the main causes of male infertility, and is classified as obstructive (OA) or non-obstructive (NOA) azoospermia based on histopathological characteristics. The molecular background of NOA is still largely unknown. DNA methylation performed by DNMTs is implicated in the transcriptional regulation of spermatogenesis-related genes. The aim of the present study was to evaluate the cellular localisation and expression levels of the DNMT1, DNMT3A and DNMT3B proteins, as well as global DNA methylation profiles in testicular biopsy samples obtained from men with various types of NOA, including hypospermatogenesis (hyposperm), round spermatid (RS) arrest, spermatocyte (SC) arrest and Sertoli cell-only (SCO) syndrome. In the testicular biopsy samples, DNMT1 expression and global DNA methylation levels decreased gradually from the hyposperm to SCO groups (P<0.05). DNMT3A expression was significantly decreased in the RS arrest, SC arrest and SCO groups compared with the hyposperm group (P<0.05). DNMT3B expression was significantly lower in the RS arrest and SCO groups than in the hyposperm group (P<0.05). Although both DNMT1 and DNMT3A were localised in the cytoplasm and nucleus of the spermatogenic cells, staining for DNMT3B was more intensive in the nucleus of spermatogenic cells. In conclusion, the findings suggest that significant changes in DNMT expression and global DNA methylation levels in spermatogenic cells may contribute to development of male infertility in the NOA groups. Further studies are needed to determine the molecular biological effects of the altered DNMT expression and DNA methylation levels on development of male infertility.

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