scholarly journals Ovarian follicle development in Booroola sheep exhibiting impaired bone morphogenetic protein signalling pathway

Reproduction ◽  
2009 ◽  
Vol 138 (4) ◽  
pp. 689-696 ◽  
Author(s):  
Chantelle Ruoss ◽  
Amanda Tadros ◽  
Tim O'Shea ◽  
Jim McFarlane ◽  
Ghanim Almahbobi
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Ovarian Function ◽  
Ovarian Follicle ◽  
Primordial Follicle ◽  
Signalling Pathway ◽  
Primordial Follicles ◽  
Merino Sheep ◽  
Ovarian Follicle Development ◽  
Morphogenetic Protein

The role of bone morphogenetic proteins (BMPs) in the regulation of ovarian function has been extensively investigated but the mechanism of regulation is not well understood. The aim of this study was to investigate the effect of mutation in the BMP receptor in Booroola sheep on the number of primordial follicles and rate of follicle recruitment in comparison with that in normal merino sheep in vivo. Whole sheep ovaries at the time of birth, 1.5 and 5 years old were collected and processed for the follicle quantification, using computerised stereological methods and statistical analyses. At birth, the total number of primordial follicles in Booroola sheep was significantly lower than in merino sheep. At 1.5 and 5 years, a reversed pattern in favour of Booroola ewes was seen with significantly more primordial follicles than merino. In parallel, the rate of primordial follicle recruitment to developing cohort was substantially lower in Booroola ewes with only 51 and 66% of primordial follicle consumption at 1.5 and 5 years respectively compared to 92 and 97% in merino ewes. On other hand, the mean numbers of developing primary follicles were smaller in Booroola sheep at the time of birth, yet, Booroola ewes possess more primary follicles than merino at 1.5 years. These findings suggest that attenuation of the intraovarian signalling pathway of BMPs may in fact be a successful means of rationalising follicle consumption, preventing unnecessary loss of follicles from the initial primordial follicle pool, hence increasing reproductive longevity and fertility.

228. In vivo evidence for a role of bone morphogenetic protein-4 in ovarian function

2005 ◽  
Vol 17 (9) ◽  
pp. 89
Author(s):  
P. S. Tanwar ◽  
J. R. McFarlane
Keyword(s):  
Bone Morphogenetic Protein ◽  
Transforming Growth Factor ◽  
Ovarian Function ◽  
Ovarian Follicle ◽  
Passive Immunization ◽  
Control Group ◽  
Bone Morphogenetic Protein 4 ◽  
Primordial Follicles ◽  
Morphogenetic Protein

Bone morphogenetic proteins (BMPs) were first identified on the basis of their bone inducing capacity, and later shown to be members of the transforming growth factor β (TGF β) super family. Nilsson et al.1 studied the effect of BMP-4 on follicular development in rat ovaries and found that the addition of BMP-4 to whole ovary cultures led to more numbers of developing primary follicles but less numbers of primordial follicles. Their studies indicate that BMP-4 acts as a transition factor for the conversion of primordial follicles to primary follicles. To test this hypothesis in-vivo, we conducted passive immunization studies against BMP-4 in prepubertal female mice. The mice were divided in to four groups (n = 5), and given daily SC injections of the following treatment: anti BMP-4 (50μg), PMSG (10 IU) (pregnant mare serum gonadotropin) with and without anti BMP-4 (0.5 mg/mL) and PBS for 3 days. All experimentation was approved by animal ethics committee, University of New England, Armidale, NSW. On the fourth day the mice were killed and the ovaries removed and weighed. The mice treated with anti BMP-4 had significantly smaller ovaries (4.1 ± 0.4 mg) than the control group (8.6 ± 0.9 mg). PMSG stimulated ovarian weight (21.0 ± 1.2 mg) but anti BMP-4 (23.2 ± 1.3 mg) did not significantly affect the weight of the stimulated ovaries. This data confirms BMP-4 is important in ovarian function; however, it is unclear whether this effect is on the ovary directly or via FSH. (1)Nilsson, E. E., Skinner, M.K. (2003). Bone morphogenetic protein-4 acts as an ovarian follicle survival factor and promotes primordial follicle development. Biology of Reproduction 69, 1265–1272.

scholarly journals Proteomic Analysis of Fetal Ovaries Reveals That Primordial Follicle Formation and Transition Are Differentially Regulated

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Mengmeng Xu ◽  
Long Che ◽  
Zhenguo Yang ◽  
Pan Zhang ◽  
Jiankai Shi ◽  
...  
Keyword(s):  
Stress Response ◽  
Molecular Mechanism ◽  
Expression Profiles ◽  
Ovarian Follicle ◽  
Primordial Follicle ◽  
Reproductive Organ ◽  
Primary Follicle ◽  
Altered Expression ◽  
Primordial Follicles ◽  
Ovarian Follicle Development

Primordial follicle formation represents a critical phase of the initiation of embryonic reproductive organ development, while the primordial follicle transition into primary follicle determines whether oestrus or ovulation will occur in female animals. To identify molecular mechanism of new proteins which are involved in ovarian development, we employed 2D-DIGE to compare the protein expression profiles of primordial follicles and primary follicles of fetal ovaries in pigs. Fetal ovaries were collected at distinct time-points of the gestation cycle (g55 and g90). The identified proteins at the g55 time-point are mainly involved in the development of anatomical structures [reticulocalbin-1 (RCN1), reticulocalbin-3 (RCN3)], cell differentiation (actin), and stress response [heterogeneous nuclear ribonucleoprotein K (HNRNPK)]. Meanwhile, at the g90 stage, the isolated proteins with altered expression levels were mainly associated with cell proliferation [major vault protein (MVP)] and stress response [heat shock-related 70 kDa protein 2 (HSPA2)]. In conclusion, our work revealed that primordial follicle formation is regulated by RCN1, RCN3, actin, and HNRNPK, while the primordial follicle transformation to primary follicle is regulated by MVP and HSPA2. Therefore, our results provide further information for the prospective understanding of the molecular mechanism(s) involved in the regulation of the ovarian follicle development.

scholarly journals PGRMC1/2 promote luteal vascularization and maintain the primordial follicles of mice

Reproduction ◽  
2018 ◽  
Author(s):  
John J Peluso ◽  
Xiufang Liu ◽  
Tracy Uliasz ◽  
Cindy A. Pru ◽  
Nicole C. Kelp ◽  
...  
Keyword(s):  
Ovarian Follicle ◽  
Adult Population ◽  
Primordial Follicle ◽  
Luteal Cell ◽  
Corpora Lutea ◽  
Mrna Levels ◽  
Follicle Growth ◽  
Primordial Follicles ◽  
Ovarian Follicle Development ◽  
Ovulatory Follicles

To determine whether conditional depletion of Progesterone Receptor Membrane Component (PGRMC) 1 and PGRMC2 affected ovarian follicle development, follicle distribution was assessed in ovaries of young (≈ 3 month-old) and middle-aged (≈6 month-old) control (Pgrmc1/2fl/fl) and double conditional PGRMC1/2 knockout (Pgrmc1/2d/d) mice. This study revealed that the distribution of primary, preantral and antral follicles was not altered in Pgrmc1/2d/d mice, regardless of the age. Although the number of primordial follicles was similar at ≈ 3 months of age, their numbers were reduced by ≈ 80% in 6-month old Pgrmc1/2d/d mice compared to age-matched Pgrmc1/2fl/fl mice. The Pgrmc1/2d/d mice were generated using Pgr-cre mice, so ablation of Pgrmc1 and Pgrmc2 in the ovary was restricted to peri-ovulatory follicles and subsequent corpora lutea (CL). In addition, the vascularization of CL was attenuated in Pgrmc1/2d/d mice, although mRNA levels of Vascular Endothelial Growth Factor A (Vegfa) were elevated. Moreover, depletion of Pgrmc1 and Pgrmc2 altered the gene expression profile in the non-luteal component of the ovary such that Vegfa expression, a stimulator of primordial follicle growth, was elevated; Kit Ligand expression, another stimulator of primordial follicle growth, was suppressed and Anti-Mullerian Hormone, an inhibitor of primordial follicle growth, was enhanced compared to Pgrmc1/2fl/fl mice. These data reveal that luteal cell depletion of Pgrmc1 and 2 alters the expression of growth factors within the non-luteal component of the ovary which could account for the premature demise of the adult population of primordial follicles.

scholarly journals The mouse Balbiani body maintains primordial follicle quiescence via RNA storage

2020 ◽  
Author(s):  
Lei Lei ◽  
Kanako Ikami ◽  
Haley Abbott ◽  
Shiying Jin
Keyword(s):  
Ovarian Function ◽  
Follicular Development ◽  
Primordial Follicle ◽  
Primordial Follicles ◽  
Mrna Decapping ◽  
Balbiani Body ◽  
Mrna Capping ◽  
Capping Enzyme ◽  
Decapping Enzyme

AbstractIn mammalian females, the transition between quiescent primordial follicles and follicular development is critical for maintaining ovarian function and reproductive longevity. In primary oocytes of mouse quiescent primordial follicles, Golgi complexes are organized into a spherical structure, the Balbiani body. Here, we show that the structure of the B-body is maintained by microtubules and actin. The B-body stores mRNA-capping enzyme and 597 mRNAs associated with mRNA-decapping enzyme 1A. Proteins encoded by these mRNAs function in enzyme binding, cellular component organization and packing of telomere ends. Pharmacological disassembly of the B-body triggers translation of stored mRNAs and activates primordial follicles in culture and in vivo mouse model. Thus, primordial follicle quiescence is maintained by the B-body, and translationally inactive B-body-stored mRNAs may be regulated by 5’-capping.

scholarly journals Bone morphogenetic protein 6 promotes FSH receptor and anti-Müllerian hormone mRNA expression in granulosa cells from hen prehierarchal follicles

Reproduction ◽  
2012 ◽  
Vol 143 (6) ◽  
pp. 825-833 ◽  
Author(s):  
O M Ocón-Grove ◽  
D H Poole ◽  
A L Johnson
Keyword(s):  
Mrna Expression ◽  
Bone Morphogenetic Proteins ◽  
Granulosa Cells ◽  
Ovarian Follicle ◽  
Follicle Development ◽  
Fsh Receptor ◽  
Ovarian Follicle Development ◽  
Morphogenetic Protein ◽  
Preovulatory Follicles ◽  
Initial Hypothesis

A growing body of literature provides evidence of a prominent role for bone morphogenetic proteins (BMPs) in regulating various stages of ovarian follicle development. Several actions for BMP6 have been previously reported in the hen ovary, yet only within postselection (preovulatory) follicles. The initial hypothesis tested herein is that BMP6 increases FSH receptor (FSHR) mRNA expression within the granulosa layer of prehierarchal (6–8 mm) follicles (6–8 GC). BMP6 mRNA is expressed at higher levels within undifferentiated (1–8 mm) follicles compared with selected (≥9 mm) follicles. Recombinant human (rh) BMP6 initiates SMAD1, 5, 8 signaling in cultured 6–8 GC and promotes FSHR mRNA expression in a dose-related fashion. In addition, a 21 h preculture with rhBMP6 followed by a 3 h challenge with FSH increases cAMP accumulation, STAR (StAR) expression, and progesterone production. Interestingly, rhBMP6 also increases expression of anti-Müllerian hormone (AMH) mRNA in cultured 6–8 GC. This related BMP family member has previously been implicated in negatively regulating FSH responsiveness during follicle development. Considering these data, we propose that among the paracrine and/or autocrine actions of BMP6 within prehierarchal follicles is the maintenance of both FSHR and AMH mRNA expression. We predict that before follicle selection, one action of AMH within granulosa cells from 6 to 8 mm follicles is to help suppress FSHR signaling and prevent premature granulosa cell differentiation. At the time of selection, we speculate that the yet undefined signal directly responsible for selection initiates FSH responsiveness. As a result, FSH signaling suppresses AMH expression and initiates the differentiation of granulosa within the selected follicle.

126. JAK/STAT SIGNALLING IN FOLLICULOGENESIS

2010 ◽  
Vol 22 (9) ◽  
pp. 44 ◽  
Author(s):  
J. M. Sutherland ◽  
R. Keightley ◽  
R. L. Robker ◽  
D. L. Russell ◽  
E. A. McLaughlin
Keyword(s):  
Target Genes ◽  
Ovarian Follicle ◽  
Current Model ◽  
Primordial Follicle ◽  
Neonatal Mouse ◽  
Signalling Pathway ◽  
Janus Kinase ◽  
Primordial Follicles ◽  
Primordial Follicle Activation ◽  
Follicle Activation

Primordial follicle activation marks the first stage of pre-pubertal ovarian folliculogenesis, and is therefore fundamental to female fertility. Entry into development is initiated by a group of pleiotropic cytokines and growth factors, originating in and acting upon both the oocyte and granulosa support cells of the ovarian follicle through the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signalling pathway. Pivotal to this process is the transcriptional regulation of target genes via STAT complexes and negative regulation by the Suppressors of Cytokine Signalling (SOCS) family of proteins. Preliminary evidence indicates that STAT3 facilitates the activation of primordial follicles, while SOCS4 counterbalances the activity of STAT3, mediating the controlled release of primordial follicles into the growing pool throughout reproductive life. Leukemia Inhibitory Factor (LIF) has been previously demonstrated as a key granulosa cell derived cytokine involved in inducing primordial follicle activation. Through both quantitative gene expression (qPCR) and immunoblotting we have demonstrated that LIF can significantly upregulate STAT3 mRNA production (~2-fold) as well as increase STAT3 protein phosphorylation within neonatal mouse ovarian explants culture. Furthermore, through the generation of a recombinant SOCS4 protein construct, and its use in subsequent protein-protein pull-downs, we were able to multiple targets involved in oocyte maturation, STAT3 interactions, and JAK/STAT signaling. These targets were also found to be significantly upregulated via qPCR analysis in neonatal mouse ovaries treated with LIF. These results support our current model for the involvement of STAT3 and SOCS4 in a basic negative feedback loop within the JAK/STAT signalling pathway that results in the regulation of primordial follicle activation and development.

scholarly journals Anti-Müllerian Hormone Attenuates the Effects of FSH on Follicle Development in the Mouse Ovary

Endocrinology ◽  
2001 ◽  
Vol 142 (11) ◽  
pp. 4891-4899 ◽  
Author(s):  
Alexandra L. L. Durlinger ◽  
Maria J. G. Gruijters ◽  
Piet Kramer ◽  
Bas Karels ◽  
T. Rajendra Kumar ◽  
...  
Keyword(s):  
Ovarian Follicle ◽  
Inhibitory Effect ◽  
Ovarian Follicles ◽  
Follicle Development ◽  
Wild Type ◽  
Follicle Growth ◽  
Primordial Follicles ◽  
Ovarian Follicle Development

Abstract Although ovarian follicle growth is under the influence of many growth factors and hormones of which FSH remains one of the most prominent regulators. Therefore, factors affecting the sensitivity of ovarian follicles to FSH are also important for follicle growth. The aim of the present study was to investigate whether anti-Müllerian hormone (AMH) has an inhibitory effect on follicle growth by decreasing the sensitivity of ovarian follicles to FSH. Furthermore, the combined action of AMH and FSH on ovarian follicle development was examined. Three different experiments were performed. Using an in vitro follicle culture system it was shown that FSH-stimulated preantral follicle growth is attenuated in the presence of AMH. This observation was confirmed by an in vivo experiment showing that in immature AMH-deficient females, more follicles start to grow under the influence of exogenous FSH than in their wild-type littermates. In a third experiment, examination of the follicle population of 4-month-old wild-type, FSHβ-, AMH-, and AMH-/FSHβ-deficient females revealed that loss of FSH expression has no impact on the number of primordial and preantral follicles, but the loss of inhibitory action of AMH on the recruitment of primordial follicles in AMH-deficient mice is increased in the absence of FSH. In conclusion, these studies show that AMH inhibits FSH-stimulated follicle growth in the mouse, suggesting that AMH is one of the factors determining the sensitivity of ovarian follicles for FSH and that AMH is a dominant regulator of early follicle growth.

scholarly journals Distinct Signaling Pathways Distinguish in vivo From in vitro Growth in Murine Ovarian Follicle Activation and Maturation

2021 ◽  
Vol 9 ◽  
Author(s):  
Mahboobeh Amoushahi ◽  
Karin Lykke-Hartmann
Keyword(s):  
Ovarian Tissue ◽  
Ovarian Follicle ◽  
Primordial Follicle ◽  
Ovarian Tissue Cryopreservation ◽  
Ros Production ◽  
Primordial Follicles ◽  
Expression Of Genes ◽  
Follicle Activation

Women with cancer and low ovarian reserves face serious challenges in infertility treatment. Ovarian tissue cryopreservation is currently used for such patients to preserve fertility. One major challenge is the activation of dormant ovarian follicles, which is hampered by our limited biological understanding of molecular determinants that activate dormant follicles and help maintain healthy follicles during growth. Here, we investigated the transcriptomes of oocytes isolated from dormant (primordial) and activated (primary) follicles under in vivo and in vitro conditions. We compared the biological relevance of the initial molecular markers of mature metaphase II (MII) oocytes developed in vivo or in vitro. The expression levels of genes involved in the cell cycle, signal transduction, and Wnt signaling were highly enriched in oocytes from primary follicles and MII oocytes. Interestingly, we detected strong downregulation of the expression of genes involved in mitochondrial and reactive oxygen species (ROS) production in oocytes from primordial follicles, in contrast to oocytes from primary follicles and MII oocytes. Our results showed a dynamic pattern in mitochondrial and ROS production-related genes, emphasizing their important role(s) in primordial follicle activation and oocyte maturation. The transcriptome of MII oocytes showed a major divergence from that of oocytes of primordial and primary follicles.

scholarly journals An epigenetic switch repressingTet1in gonadotropes activates the reproductive axis

2017 ◽  
Vol 114 (38) ◽  
pp. 10131-10136 ◽  
Author(s):  
Yahav Yosefzon ◽  
Cfir David ◽  
Anna Tsukerman ◽  
Lilach Pnueli ◽  
Sen Qiao ◽  
...  
Keyword(s):  
Ovarian Function ◽  
Ovarian Follicle ◽  
Gene Promoter ◽  
Follicle Development ◽  
Mrna Levels ◽  
Epigenetic Switch ◽  
Ovarian Follicle Development ◽  
Reproductive Axis ◽  
Poorly Differentiated ◽  
Tet Enzymes

The TET enzymes catalyze conversion of 5-methyl cytosine (5mC) to 5-hydroxymethyl cytosine (5hmC) and play important roles during development. TET1 has been particularly well-studied in pluripotent stem cells, butTet1-KO mice are viable, and the most marked defect is abnormal ovarian follicle development, resulting in impaired fertility. We hypothesized that TET1 might play a role in the central control of reproduction by regulating expression of the gonadotropin hormones, which are responsible for follicle development and maturation and ovarian function. We find that all three TET enzymes are expressed in gonadotrope-precursor cells, butTet1mRNA levels decrease markedly with completion of cell differentiation, corresponding with an increase in expression of the luteinizing hormone gene,Lhb. We demonstrate that poorly differentiated gonadotropes express a TET1 isoform lacking the N-terminal CXXC-domain, which repressesLhbgene expression directly and does not catalyze 5hmC at the gene promoter. We show that this isoform is also expressed in other differentiated tissues, and that it is regulated by an alternative promoter whose activity is repressed by the liganded estrogen and androgen receptors, and by the hypothalamic gonadotropin-releasing hormone through activation of PKA. Its expression is also regulated by DNA methylation, including at an upstream enhancer that is protected by TET2, to allowTet1expression. The down-regulation of TET1 relieves its repression of the methylatedLhbgene promoter, which is then hydroxymethylated and activated by TET2 for full reproductive competence.

scholarly journals Oocyte-Specific Overexpression of Mouse Bone Morphogenetic Protein-15 Leads to Accelerated Folliculogenesis and an Early Onset of Acyclicity in Transgenic Mice

Endocrinology ◽  
2008 ◽  
Vol 149 (6) ◽  
pp. 2807-2815 ◽  
Author(s):  
Heather E. McMahon ◽  
Osamu Hashimoto ◽  
Pamela L. Mellon ◽  
Shunichi Shimasaki
Keyword(s):  
Transgenic Mice ◽  
Bone Morphogenetic Protein ◽  
Early Onset ◽  
Ovarian Function ◽  
Chimeric Protein ◽  
Mature Protein ◽  
Follicle Growth ◽  
Morphogenetic Protein

Whereas mutations in the bmp15 gene cause infertility in ewes and women due to defects in folliculogenesis, most defects in female mice lacking bone morphogenetic protein (BMP)-15 are confined to the ovulation process, supportive of the observation that functional mouse BMP-15 is barely detected in oocytes in vivo until after the LH surge. In addition, the mouse BMP-15 proprotein is not processed into the functional mature protein in transfected cells. However, a chimeric protein consisting of the human proregion, human cleavage site, and mouse mature region (termed hhmBMP-15) is processed and the mature protein secreted. To study the role of BMP-15 in folliculogenesis, we generated transgenic mice overexpressing hhmBMP-15, exclusively in oocytes during folliculogenesis and confirmed the overexpression of mouse BMP-15 mature protein. Immature transgenic mice exhibited accelerated follicle growth with decreased primary follicles and an increase in secondary follicles. Granulosa cells of immature mice displayed an increased mitotic index and decreased FSH receptor mRNA expression. Adult mice had normal litter sizes but an increased number of atretic antral follicles. Interestingly, aging mice exhibited an early onset of acyclicity marked by increased diestrus length and early occurrence of constant diestrus. These findings indicate the role of BMP-15 in vivo in promoting follicle growth and preventing follicle maturation, resulting in an early decline in the ovarian reserve of transgenic mice. Therefore, the lack of mouse BMP-15 during early folliculogenesis in the wild-type mice may be relevant to their polyovulatory nature as well as the preservation of ovarian function as the mice age.

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