scholarly journals 202.Estrogen actions on follicle formation and early follicle development

2004 ◽  
Vol 16 (9) ◽  
pp. 202
Author(s):  
K. L. Britt ◽  
P. K. Saunders ◽  
S. J. McPherson ◽  
M. L. Misso ◽  
E. R. Simpson ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Proliferating Cell Nuclear Antigen ◽  
Leydig Cells ◽  
Follicular Development ◽  
Primordial Follicle ◽  
Nuclear Antigen ◽  
Proliferative Index ◽  
Mouse Ovary ◽  
Primordial Follicles ◽  
Proliferating Cell

Estradiol 17 beta (E2) effects late follicular development whilst primordial follicle formation and early activation are thought to be independent of E2. To test this hypothesis we compared numbers of primordial and primary follicles in wildtype and E2 deficient ArKO mice, and the immunohistochemical staining or mRNA expression of Mullerian inhibiting substance (MIS), Wilms tumour 1 (WT-1), and growth differentiation factor (GDF9), known to effect early follicular differentiation. Proliferating cell nuclear antigen (PCNA) staining was a marker of proliferative index. The effects of E2 replacement for 3 wk in 7 wk old ArKO and wildtype mice on these parameters were also tested. We used unbiased, assumption-free stereological methods for quantification of early follicular numbers in the mouse ovary (1). ArKO mice had reduced numbers of primordial and primary follicles compared to wildtype (63%, p<0.001 and 60%, p=0.062 of Wt respectively). This reduction was not corrected by E2 treatment, suggesting that E2 effects the initial formation or activation of primordial follicles. There was a significant increase in the diameters of the oocytes in primordial follicles of ArKO mice compared to wildtype. There were no differences in the immunostaining of MIS, WT-1 and PCNA in primordial and primary follicles between wildtype and ArKO mice. The only difference was as a consequence of Sertoli and Leydig cells in ovaries of ArKO mice. GDF9 mRNA expression was markedly increased in ArKO ovaries. E2 treatment restored the ovarian follicular morphology, and consequently the immunostaining patterns, but had no effect on early follicle numbers. In conclusion, E2 has a role in controlling the size of the oocyte and primordial follicle pools in mice. Supported by NH&MRC RegKey #241000 and 198705. (1) Britt and Myers (2004) Reproduction 127,:569–580.

scholarly journals microRNA 376a regulates follicle assembly by targeting Pcna in fetal and neonatal mouse ovaries

Reproduction ◽  
2014 ◽  
Vol 148 (1) ◽  
pp. 43-54 ◽  
Author(s):  
Huan Zhang ◽  
Xiaohua Jiang ◽  
Yuanwei Zhang ◽  
Bo Xu ◽  
Juan Hua ◽  
...  
Keyword(s):  
Proliferating Cell Nuclear Antigen ◽  
Primordial Follicle ◽  
Neonatal Mouse ◽  
Nuclear Antigen ◽  
Mrna Levels ◽  
Microrna Target ◽  
Ovarian Insufficiency ◽  
Primordial Follicles ◽  
Reproductive Life ◽  
Proliferating Cell

In mammals, the primordial follicle pool, providing all oocytes available to a female throughout her reproductive life, is established perinatally. Dysregulation of primordial follicle assembly results in female reproductive diseases, such as premature ovarian insufficiency and infertility. Female mice lackingDicer1(Dicer), a gene required for biogenesis of microRNAs, show abnormal morphology of follicles and infertility. However, the contribution of individual microRNAs to primordial follicle assembly remains largely unknown. Here, we report that microRNA 376a (miR-376a) regulates primordial follicle assembly by modulating the expression of proliferating cell nuclear antigen (Pcna), a gene we previously reported to regulate primordial follicle assembly by regulating oocyte apoptosis in mouse ovaries. miR-376a was shown to be negatively correlated withPcnamRNA expression in fetal and neonatal mouse ovaries and to directly bind toPcnamRNA 3′ untranslated region. Cultured 18.5 days postcoitum mouse ovaries transfected with miR-376a exhibited decreasedPcnaexpression both in protein and mRNA levels. Moreover, miR-376a overexpression significantly increased primordial follicles and reduced apoptosis of oocytes, which was very similar to those in ovaries co-transfected with miR-376a and siRNAs targetingPcna. Taken together, our results demonstrate that miR-376a regulates primordial follicle assembly by modulating the expression ofPcna. To our knowledge, this is the first microRNA–target mRNA pair that has been reported to regulate mammalian primordial follicle assembly and further our understanding of the regulation of primordial follicle assembly.

scholarly journals Assessment of follicular development in cryopreserved primate ovarian tissue by xenografting: prepubertal tissues are less sensitive to the choice of cryoprotectant

Reproduction ◽  
2011 ◽  
Vol 141 (4) ◽  
pp. 481-490 ◽  
Author(s):  
V von Schönfeldt ◽  
R Chandolia ◽  
L Kiesel ◽  
E Nieschlag ◽  
S Schlatt ◽  
...  
Keyword(s):  
Cancer Survival ◽  
Ovarian Tissue ◽  
Survival Rates ◽  
Follicular Development ◽  
Nuclear Antigen ◽  
Primate Model ◽  
Primordial Follicles ◽  
Cellular Compartments ◽  
Proliferating Cell ◽  
Human Primate

Improvements in cancer survival rates have renewed interest in the cryopreservation of ovarian tissue for fertility preservation. We used the marmoset as a non-human primate model to assess the effect of different cryoprotectives on follicular viability of prepubertal compared to adult ovarian tissue following xenografting. Cryopreservation was performed with dimethylsulfoxide (DMSO), 1,2-propanediol (PrOH), or ethylene glycol (EG) using a slow freezing protocol. Subsequently, nude mice received eight grafts per animal from the DMSO and the PrOH groups for a 4-week grafting period. Fresh, cryopreserved–thawed, and xenografted tissues were serially sectioned and evaluated for the number and morphology of follicles. In adult tissue, the percentage of morphologically normal primordial follicles significantly decreased from 41.2±4.5% (fresh) to 13.6±1.8 (DMSO), 9.5±1.7 (PrOH), or 6.8±1.0 (EG) following cryopreservation. After xenografting, the percentage of morphologically normal primordial (26.2±2.5%) and primary follicles (28.1±5.4%) in the DMSO group was significantly higher than that in the PrOH group (12.2±3 and 5.4±2.1% respectively). Proliferating cell nuclear antigen (PCNA) staining suggests the resumption of proliferative activity in all cellular compartments. In prepubertal tissues, primordial but not primary follicles display a similar sensitivity to cryopreservation, and no significant differences between DMSO and PrOH following xenografting were observed. In conclusion, DMSO shows a superior protective effect on follicular morphology compared with PrOH and EG in cryopreserved tissues. Xenografting has confirmed better efficacy of DMSO versus PrOH in adult but not in prepubertal tissues, probably owing to a greater capacity of younger animals to compensate for cryoinjury.

Follistatin but not α or βA inhibin subunit mRNA is expressed in ovine fetal ovaries in late gestation

1994 ◽  
Vol 13 (1) ◽  
pp. 1-9 ◽  
Author(s):  
R Braw-Tal ◽  
D J Tisdall ◽  
N L Hudson ◽  
P Smith ◽  
K P McNatty
Keyword(s):  
Mrna Expression ◽  
Granulosa Cells ◽  
Cell Function ◽  
Follicular Development ◽  
Primordial Follicle ◽  
Late Gestation ◽  
Follicle Growth ◽  
Primordial Follicles ◽  
Fetal Ovary ◽  
Ovine Fetal

ABSTRACT The aim of this study was to investigate the sites of follistatin and α and βA inhibin mRNA expression in the ovaries of female sheep fetuses at 90, 100, 120 and 135 days of gestation (term=day 147). At 90 and 100 days primordial follicles were formed, followed by the appearance of primary follicles at 100 days of gestation. At days 120 and 135, primordial, primary and preantral (i.e. secondary) follicles were present in the ovaries, but antral (i.e. tertiary) follicles were not observed at any of these gestational ages. Two Booroola genotypes were studied: homozygous carriers (BB) and non-carriers (++) of the fecundity gene (FecB). Irrespective of genotype no specific hybridization of the α and βA inhibin riboprobes was detected in any ovarian cells at days 90, 100, 120 or 135 of gestation. In control mature ovaries, on the other hand, strong hybridization in the granulosa cells of antral follicles was observed. In contrast to α and βA inhibin, follistatin antisense (but not sense) riboprobes hybridized specifically to the granulosa cells of preantral follicles with two or more layers of cells at days 120 and 135 of gestation. Moreover, hybridization was also evident in the cells of the ovarian rete at days 120 and 135, but not at 90 or 100 days. No follistatin mRNA expression was observed in the granulosa cells of primordial or primary follicles or in any other ovarian cell type at any of the gestational ages examined. No FecB-specific differences in follistatin expression were noted with respect to stage of preantral follicular development and there were no obvious differences in the intensity of expression. These results show that follistatin mRNA is expressed specifically in the granulosa cells and intraovarian rete. Expression of follistatin in rete cells was coincident with the increasing numbers of growing follicles within the fetal ovary, indicating that rete cell function may have a role in the ontogeny of early follicular growth. Our results suggest that follistatin and α and βA inhibin may not be important for the initiation of follicle growth in the sheep ovary, since these genes are not expressed during the transformation of a primordial follicle to a primary structure. However, the evidence for follistatin mRNA expression in the ovine fetal ovary implies that this hormone is likely to play a role during the early stages of follicle growth.

scholarly journals Increased endothelin and endothelin receptor mRNA expression in polycystic kidneys of cpk mice.

1993 ◽  
Vol 4 (4) ◽  
pp. 1064-1072 ◽  
Author(s):  
T Nakamura ◽  
I Ebihara ◽  
M Fukui ◽  
S Osada ◽  
Y Tomino ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Transforming Growth Factor Beta ◽  
Proliferating Cell Nuclear Antigen ◽  
Transforming Growth Factor ◽  
Nuclear Antigen ◽  
Tnf Alpha ◽  
Mrna Levels ◽  
Tgf Beta ◽  
Receptor Mrna ◽  
Proliferating Cell

The renal mRNA levels of endothelin (ET)-1 and ET-3 and for ET receptors A and B were measured in the cystic kidneys of cpk/cpk mice at 1, 2, and 3 wk of age. At 1 wk of age, renal ET-1 mRNA was 3.2-fold greater in cystic mice than in controls and continued to increase with the progression of cyst formation to reach 10.4-fold more than controls at 3 wk. ET-3 mRNA levels did not differ between cystic and control mice. Renal ETA and ETB receptor mRNA increased gradually in cystic mice with the progression of their cysts, reaching 4.2- and 6.3-fold increases over controls, respectively, at 3 wk. Proliferating cell nuclear antigen mRNA expression was also examined, and proliferating cell nuclear antigen mRNA levels were found to be significantly increased in the kidneys of cystic mice compared with controls: 2. 1-fold at 1 wk, 4.5-fold at 2 wk, and 7.8-fold at 3 wk. The mRNA levels for transforming growth factor beta (TGF-beta) and tumor necrosis factor alpha (TNF-alpha) in the kidneys of cystic mice were also examined and were found to be increased progressively with age (TGF-beta, 2.1-fold at 1 wk, 4.2-fold at 2 wk, and 6.2-fold at 3 wk; TNF-alpha, 2.2-fold at 1 wk, 3.8-fold at 2 wk, and 5.4-fold at 3 wk).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Positive autoregulation of c-myb expression via Myb binding sites in the 5' flanking region of the human c-myb gene.

1991 ◽  
Vol 11 (12) ◽  
pp. 6166-6176 ◽  
Author(s):  
N C Nicolaides ◽  
R Gualdi ◽  
C Casadevall ◽  
L Manzella ◽  
B Calabretta
Keyword(s):  
Mrna Expression ◽  
Binding Sites ◽  
Proliferating Cell Nuclear Antigen ◽  
Nuclear Antigen ◽  
Myb Gene ◽  
First Intron ◽  
Flanking Sequences ◽  
Flanking Region ◽  
Myb Protein ◽  
Proliferating Cell

The nuclear proto-oncogene c-myb is preferentially expressed in lymphohematopoietic cells, in which it plays an important role in the processes of differentiation and proliferation. The mechanism(s) that regulates c-myb expression is not fully understood, although in mouse cells a regulatory mechanism involves a transcriptional block in the first intron. To analyze the contribution of the 5' flanking sequences in regulating the expression of the human c-myb gene, we isolated a genomic clone containing extensive 5' flanking sequences, the first exon, and a large portion of the first intron. Sequence analysis of a subcloned 1.3-kb BamHI insert corresponding to 687 nucleotides of the 5' flanking sequence, the entire first exon, and 300 nucleotides of the first intron revealed the presence of closely spaced putative Myb binding sites within a segment extending from nucleotides -616 to -575 upstream from the cap site. A 165-bp segment containing these putative Myb binding sites was linked to a human thymidine kinase (TK) cDNA driven by a low-activity proliferating cell nuclear antigen promoter and cotransfected into TK- ts13 cells with a plasmid in which a full-length human c-myb cDNA is driven by the early simian virus 40 promoter; Myb inducibility of TK mRNA expression was observed both in transient expression assays and in stable transformants. The highest level of inducibility was detected when the 165-bp fragment was placed 138 bp upstream of the proliferating cell nuclear antigen promoter-TK cDNA reporter unit or 3' of the TK cDNA. Mutation of the putative Myb binding sites greatly reduced c-myb transactivation of TK mRNA expression and specifically reduced the binding of in vitro-translated Myb protein at those sites. Finally, c-myb transactivated TK mRNA expression driven by a segment of the authentic c-myb 5' flanking region containing the Myb binding sites. These data suggest that human c-myb maintains high levels of Myb protein in cells that require this gene product for proliferation and/or differentiation by an autoregulatory mechanism involving Myb binding sites in the 5' flanking region.

scholarly journals Insights into the Protective Mechanisms of Tamoxifen in Radiotherapy-Induced Ovarian Follicular Loss: Impact on Insulin-Like Growth Factor 1

Endocrinology ◽  
2013 ◽  
Vol 154 (10) ◽  
pp. 3888-3899 ◽  
Author(s):  
Yasmen F. Mahran ◽  
Ebtehal El-Demerdash ◽  
Ahmed S. Nada ◽  
Azza A. Ali ◽  
Ashraf B. Abdel-Naim
Keyword(s):  
Oxidative Stress ◽  
Proliferating Cell Nuclear Antigen ◽  
Follicular Development ◽  
Ovarian Failure ◽  
Radioprotective Effect ◽  
Whole Body ◽  
Nuclear Antigen ◽  
Γ Irradiation ◽  
Protective Mechanisms ◽  
Proliferating Cell

Radiotherapy is one of the most common and effective cancer treatments. However, it has a profound impact on ovarian function, leading to premature ovarian failure. With the hope of preserving fertility in cancer survivors, the need for an effective radioprotective therapy is evident. The present study investigated the mechanism of the potential radioprotective effect of tamoxifen (TAM) on γ-irradiation-induced ovarian failure on experimental rats and the impact of the IGF-1 in the underlying protective mechanisms. Female Sprague Dawley rats were either exposed to single whole-body irradiation (3.2 Gy; lethal dose [LD20]) and/or treated with TAM (1 mg/kg). γ-Irradiation caused an array of ovarian dysfunction that was evident by assessment of hormonal changes, follicular development, proliferation marker (proliferating cell nuclear antigen), and oxidative stress as well as apoptotic markers. In addition, IGF-1/IGF-1 receptor axis expression was assessed using real-time RT-PCR and immunolocalization techniques. Furthermore, fertility assessment was performed. TAM significantly enhanced follicular development and restored the anti-Mullerian hormone level. Moreover, it ameliorated the deleterious effects of irradiation on oxidative stress, proliferating cell nuclear antigen expression, and apoptosis. Interestingly, TAM was shown to enhance the ovarian IGF-1 but not IGF-1 receptor, a property that contributed significantly to its radioprotective mechanisms. Finally, TAM regained the fertility that was lost after irradiation. In conclusion, TAM showed a radioprotective effect and saved the ovarian reserve and fertility through increasing anti-Mullerian hormone and the local IGF-1 level and counteracting the oxidative stress-mediated apoptosis.

scholarly journals NTRK1 and NTRK2 receptors facilitate follicle assembly and early follicular development in the mouse ovary

Reproduction ◽  
2009 ◽  
Vol 138 (1) ◽  
pp. 131-140 ◽  
Author(s):  
Bredford Kerr ◽  
Cecilia Garcia-Rudaz ◽  
Mauricio Dorfman ◽  
Alfonso Paredes ◽  
Sergio R Ojeda
Keyword(s):  
Ovarian Development ◽  
Follicular Development ◽  
Primordial Follicle ◽  
Tyrosine Kinase Receptors ◽  
Wild Type ◽  
Mouse Ovary ◽  
Cell Cycle Protein ◽  
Primordial Follicles ◽  
A Cell ◽  
The Common

Recent studies have demonstrated that neurotrophins (NTs) and their NTRK tyrosine kinase receptors, thought to be exclusively required for the development of the nervous system, are also involved in controlling ovarian development. Here, we show that primordial follicle formation is decreased in the absence of nerve growth factor (NGF) or its receptor NTRK1, and in the absence of NTRK2, the receptor for neurotrophin-4 (NTF4) and brain-derived neurotrophic factor (BDNF). This deficiency is not due to premature oocyte loss, because the ovaries ofNtrk1−/−andNtrk2−/−mice do not show an increased rate of oocyte death antedating the initiation of folliculogenesis. Moreover, exposure of NGF-deficient ovaries to NGF rescues the defect in follicular assembly, if NTRK1 receptors are present, suggesting that the absence of NTs causes a delay, and not an irretrievable loss, of follicle formation. Both the number of secondary follicles and FSH receptor (FSHR) expression are diminished inNtrk1- andNtrk2-null ovaries, but not in ovaries lacking the common NT receptor NGFR. Transient exposure of wild-type ovaries to NTF4 increasesFshrgene expression and enhances the ability of the ovary to respond to FSH with formation of cyclin D2, a cell cycle protein mediating the proliferative actions of FSH in the ovary. These results indicate that both NTRK1 and NTRK2 receptors are necessary for the timely assembly of primordial follicles and for sustaining early follicular development. They also suggest that a mechanism by which NTRK2 receptors facilitate subsequent follicle development is by inducing the formation of functional FSHR.

Sign in / Sign up

Export Citation Format

Share Document