scholarly journals Insulin-like growth factor 2 is produced by antral follicles and promotes preantral follicle development in macaques

2020 ◽  
Author(s):  
Olena Y Tkachenko ◽  
Shally Wolf ◽  
Maralee S Lawson ◽  
Alison Y Ting ◽  
Jhenifer K Rodrigues ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Granulosa Cell ◽  
Steroid Hormone ◽  
Follicle Development ◽  
Hormone Regulation ◽  
Preantral Follicle ◽  
Paracrine Factor ◽  
Preantral Follicles ◽  
Antral Follicles ◽  
And Function

Abstract Insulin-like growth factors (IGFs) are known for their involvement in endocrine and paracrine regulation of ovarian function. While IGF2 is the predominant circulating and intra-ovarian form of IGFs in primate species, the stage-specific follicular expression, action and regulation of IGF2 are not well defined. Therefore, experiments were conducted to investigate the follicular IGF production in response to steroid hormone regulation and the direct IGF actions on follicular development and function in vitro. Preantral follicles were isolated from rhesus macaque ovaries and cultured to the antral stage in media supplemented with follicle-stimulating hormone and insulin. Follicles were randomly assigned to treatment groups: (a) control, (b) trilostane (a steroid synthesis inhibitor), (c) trilostane + estradiol, (d) trilostane + progesterone, and (e) trilostane + dihydrotestosterone. Media was analyzed for IGF concentrations, which were correlated to follicle growth. Follicles produced IGF2, but not IGF1, at the antral stage. Steroid depletion decreased, while steroid replacement increased, IGF2 production by antral follicles. Media IGF2 levels correlated positively with antral follicle diameters. Macaque preantral follicles and granulosa cells were subsequently cultured without (control) and with recombinant human IGF2 supplementation. Follicle survival, growth and paracrine factor production, as well as granulosa cell proliferation and gonadotropin receptor gene expression, were assessed. IGF2 addition increased follicle survival rates, diameters and inhibin B production, as well as granulosa cell proliferation. These data demonstrate that IGF2 produced by antral follicles, in response to steroid hormone regulation, could act as a paracrine factor that positively impacts preantral follicle development and function in primates.

Effects of follicular fluids on the growth of porcine preantral follicle and oocyte

Zygote ◽  
2008 ◽  
Vol 16 (3) ◽  
pp. 239-247 ◽  
Author(s):  
T. Metoki ◽  
H. Iwata ◽  
M. Itoh ◽  
M. Kasai ◽  
A. Takajyo ◽  
...  
Keyword(s):  
Calf Serum ◽  
Follicle Development ◽  
Preantral Follicle ◽  
Promoting Effect ◽  
Oocyte Growth ◽  
Preantral Follicles ◽  
Molecular Weights ◽  
Heat Treated ◽  
Growth Promoting ◽  
Follicular Fluids

SummaryWe examined the effect of supplementing the culture medium with follicular fluid (FF) on the growth of porcine preantral follicles and oocytes. Firstly, preantral follicles were retrieved from ovaries and then FF was collected from all antral follicles that were 2–7 mm in diameter (AFF), which included large follicles of 4–7 mm in diameter (LFF) and small follicles of 2–3 mm in diameter (SFF). When preantral follicles with a diameter of 250 μm were cultured in medium containing AFF, the growth of follicles and oocytes was greater than when follicles were cultured in medium containing fetal calf serum (FCS). When this growth-promoting effect in AFF was compared for LFF and SFF, the LFF were shown to be significantly more effective than SFF. This LFF effect was lost, however, when the concentration of LFF in the medium was decreased from 5% to 0.5% or when LFF were heat treated (60 °C for 30 min) or trypsin was added. In contrast, a decrease in SFF concentration from 5% to 0.5% and heat treatment of the SFF enhanced preantral follicle growth. Furthermore, proteins obtained from LFF that had molecular weights greater than 10 kDa (LFF > 10 kDa) had similar, but relatively reduced, growth-promoting properties. The remaining three LFF protein fractions (<10 kDa or <100 kDa or >100 kDa), however, did not have these growth-promoting properties. In conclusion, the supplementation of medium with LFF, rather than serum, enhanced preantral follicle and oocyte growth. Factors that enhanced follicle development in LFF and factors that suppressed follicle development in SFF were proteins and these LFF factors ranged in size from 10 kDa to over 100 kDa.

scholarly journals Human BM-MSC secretome enhances human granulosa cell proliferation and steroidogenesis and restores ovarian function in primary ovarian insufficiency mouse model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hang-soo Park ◽  
Rishi Man Chugh ◽  
Abdeljabar El Andaloussi ◽  
Elie Hobeika ◽  
Sahar Esfandyari ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mouse Model ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Cellular Proliferation ◽  
Ovarian Function ◽  
Human Mesenchymal Stem Cells ◽  
Primary Ovarian Insufficiency ◽  
Ovarian Insufficiency ◽  
And Function

AbstractPrimary ovarian insufficiency (POI) is defined as the loss of ovarian function before 40 years of age. It clinically manifests as amenorrhea, infertility, and signs of estrogen insufficiency. POI is frequently induced by chemotherapy. Gonadotoxic chemotherapy reagents damage granulosa cells, which are essential for follicular function and development. Our recently published studies demonstrated that intraovarian transplantation of human mesenchymal stem cells (hMSCs) can restore fertility in a chemotherapy-induced POI mouse model. However, the regenerative mechanism underlying the hMSC effect in POI mice is not fully understood. Here, we report that the hMSC secretome increased the proliferation of human granulosa cells (HGrC1). We showed by FACS analysis that treatment of HGrC1 cells with hMSC-conditioned media (hMSC CM) stimulates cellular proliferation. We also demonstrated that the expression of steroidogenic enzymes involved in the production of estrogen, CYP19A1 and StAR, are significantly elevated in hMSC CM-treated HGrC1 cells. Our data suggest that hMSC CM stimulates granulosa cell proliferation and function, which may explain the therapeutic effect of hMSCs in our chemotherapy-induced POI animal model. Our findings indicate that the hMSC secretome may be a novel treatment approach for restoring granulosa cell and ovarian function in patients with POI.

123. ACTIVIN A AND OVARIAN FOLLICLE DEVELOPMENT

2009 ◽  
Vol 21 (9) ◽  
pp. 42
Author(s):  
D. A. Cossigny (Rosairo) ◽  
J. K. Findlay ◽  
A. E. Drummond
Keyword(s):  
Ovarian Follicle ◽  
Combined Treatment ◽  
Rna Extraction ◽  
Activin A ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Follicle Development ◽  
Preantral Follicle ◽  
Primary Follicle ◽  
Preantral Follicles ◽  
Ovarian Follicle Development

A significant developmental stage in ovarian folliculogenesis is the acquisition of gonadotropin sensitivity by ovarian follicles. Activin has previously been suggested to be involved in the responsiveness of granulosa cells to FSH (1). Therefore, the role of activin was investigated using a ‘physiological’ culture system to determine if pathways exist to transduce activin signals within the postnatal rat ovary. Organ cultures with day 4 whole ovaries were employed in order to assess the potential impact of Activin A on follicle growth and transition from the primordial through to the primary and later preantral stages of development. Ovaries were isolated and cultured for 10 days with the addition of supplemented DMEM/Hams F-12 media (2)and either FSH (100ng/ml), Activin A (50ng/ml), or a combination of the two. Media and treatments were refreshed every alternate day. At the end of the culture period, ovaries were fixed and sectioned, or placed immediately into Ultraspec for RNA extraction for future real-time PCR. Sections were used for morphological assessment and ovarian follicle counting of primordial, primary and preantral follicles. An evaluation of atresia by the detection of apoptotic cells was undertaken using terminal deoxynucleotidyl transferase (TdT) mediated dUTP-biotin nick-end labeling (TUNEL). Primary follicle numbers increased significantly (P<0.05) in the combined treatment group whereas, preantral follicle numbers increased significantly (P<0.0001) when treated with Activin A alone. This is consistent with a morphological appraisal of atresia where a decrease in atresia was found in primordial and primary follicles, supporting the primary follicle development data and Activin A treatment alone resulted in more healthy primary and preantral follicles than atretic ones. Therefore, a stimulatory role for Activin A both in the presence of FSH (primary follicle development) or alone (preantral follicle development) has resulted in more follicles making the transition from the primordial to primary stages, as well as to the later preantral stages.

Effect of hypothyroidism on ovarian follicular development, granulosa cell proliferation and peripheral hormone levels in the prepubertal rat

1996 ◽  
Vol 134 (5) ◽  
pp. 649-654 ◽  
Author(s):  
Grietje Dijkstra ◽  
Dirk G de Rooij ◽  
Frank H de Jong ◽  
Robert van den Hurk
Keyword(s):  
Cell Proliferation ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Ovarian Development ◽  
Follicular Development ◽  
Corpora Lutea ◽  
Hormone Levels ◽  
Antral Follicles ◽  
Ovarian Follicular Development ◽  
Serum Tsh

Dijkstra G, de Rooij DG, de Jong FH, van den Hurk R. Effect of hypothyroidism on ovarian follicular development, granulosa cell proliferation and peripheral hormone levels in the prepubertal rat. Eur J Endocrinol 1996;134:649–54. ISSN 0804–4643 The aim of this study was to examine the effects of prepubertal hypothyroidism on ovarian development in rats. Therefore, from birth up to day 40 postpartum, rats were given 6-propyl-2-thiouracil (PTU) via the drinking water of mothers and pups. At ages ranging from 12 to 40 days, ovarian weights were measured and serum was collected to estimate thyrotrophin (TSH), folliclestimulating hormone (FSH) and inhibin levels. Two hours before sacrifice the animals received an injection of bromodeoxyuridine (BrdU) to estimate the proliferative activity of the follicular granulosa cells. Ovaries were fixed in Carnoy's fluid and follicle counts were performed on sections stained with anti-BrdU and with haematoxylin and eosin. The PTU treatment resulted in increased serum TSH levels, indicative of hypothyroidism, and markedly lower body and ovarian weights, whereas serum FSH and inhibin levels were hardly affected. At day 40, ovaries of PTU-treated animals contained relatively more secondary and less antral follicles, smaller non-atretic antral follicles and more atretic follicles when compared with untreated rats, while corpora lutea were absent. It is concluded that this disturbed folliculogenesis is due to inadequate thyroid hormone supply, which hampers the differentiation and not the proliferation of granulosa cells because diameters of antral follicles were significantly smaller whereas the BrdU-labelling index had not changed. Robert van den Hurk, Department of Functional Morphology, Faculty of Veterinary Medicine, PO Box 80.157, 3508 TD Utrecht, The Netherlands

scholarly journals Synergistic inhibition of csal1 and csal3 in granulosa cell proliferation and steroidogenesis of hen ovarian prehierarchical development†

2019 ◽  
Vol 101 (5) ◽  
pp. 986-1000 ◽  
Author(s):  
Hongyan Zhu ◽  
Ning Qin ◽  
Xiaoxing Xu ◽  
Xue Sun ◽  
Xiaoxia Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Molecular Mechanisms ◽  
Current Data ◽  
Follicle Development ◽  
Translocation Mechanism ◽  
Development In Vitro

Abstract SALL1 and SALL3 are transcription factors that play an essential role in regulating developmental processes and organogenesis in many species. However, the functional role of SALL1 and SALL3 in chicken prehierarchical follicle development is unknown. This study aimed to explore the potential role and mechanism of csal1 and csal3 in granulosa cell proliferation, differentiation, and follicle selection within the prehierarchical follicles of hen ovary. Our data demonstrated that the csal1 and csal3 transcriptions were highly expressed in granulosa cells of prehierarchical follicles, and their proteins were mainly localized in the cytoplasm of granulosa cells and oocytes as well as in the ovarian stroma and epithelium. It initially revealed that both csal1 and csal3 may be involved in chicken prehierarchical follicle development via a translocation mechanism. Furthermore, our results showed an abundance of CCND1, Bcat, StAR, CYP11A1, and FSHR mRNA in granulosa cells, and the proliferation levels of granulosa cells from the prehierarchical follicles were significantly increased by siRNA-mediated knockdown of csal1 or/and csal3. Conversely, the overexpression of csal1 or/and csal3 in the granulosa cells led to a remarkably decreased of them. Moreover, csal1 and csal3 together exert a much stronger effect on the regulation than any of csal1 or csal3. These results indicated that csal1 and csal3 play synergistic inhibitory roles on granulosa cell proliferation, differentiation, and steroidogenesis during prehierarchical follicle development in vitro. The current data provide a basis of molecular mechanisms of csal1 and csal3 in controlling the prehierarchical follicle development and growth of hen ovary in vivo.

scholarly journals In ovaries with high or low variation in follicle size, granulosa cells of antral follicles exhibit distinct size-related processes

2019 ◽  
Vol 25 (10) ◽  
pp. 614-624 ◽  
Author(s):  
N G J Costermans ◽  
J Keijer ◽  
E M van Schothorst ◽  
B Kemp ◽  
S Keshtkar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Antral Follicle ◽  
Ivf Outcome ◽  
Negative Consequences ◽  
Antral Follicles ◽  
Follicle Size

Abstract Antral follicle size might be a valuable additive predictive marker for IVF outcome. To better understand consequences of antral follicle size as a marker for reproductive outcome, we aimed to obtain insight in follicle size-related granulosa cell processes, as granulosa cells play an essential role in follicular development via the production of growth factors, steroids and metabolic intermediates. Using the pig as a model, we compared gene expression in granulosa cells of smaller and larger follicles in the healthy antral follicle pool of sows, which had a high variation versus low variation in follicle size. Selected gene expression was confirmed at the protein level. Granulosa cells of smaller antral follicles showed increased cell proliferation, which was accompanied by a metabolic shift towards aerobic glycolysis (i.e. the Warburg effect), similar to other highly proliferating cells. High granulosa cell proliferation rates in smaller follicles might be regulated via increased granulosa cell expression of the androgen receptor and the epidermal growth factor receptor, which are activated in response to locally produced mitogens. While granulosa cells of smaller follicles in the pool are more proliferative, granulosa cells of larger follicles express more maturation markers such as insulin-like growth factor-1 (IGF1) and angiopoietin 1 (ANGPT1) and are therefore more differentiated. As both higher IGF1 and ANGPT1 have been associated with better IVF outcomes, the results of our study imply that including smaller follicles for oocyte aspiration might have negative consequences for IVF outcome.

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