scholarly journals Growth Differentiation Factor-9 Mediates Follicle-Stimulating Hormone-Thyroid Hormone Interaction in the Regulation of Rat Preantral Follicular Development

Endocrinology ◽  
2009 ◽  
Vol 150 (12) ◽  
pp. 5566-5574 ◽  
Author(s):  
Noriko Kobayashi ◽  
Makoto Orisaka ◽  
Mingju Cao ◽  
Fumikazu Kotsuji ◽  
Arthur Leader ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Direct Action ◽  
Follicular Development ◽  
Reproductive Function ◽  
Normal Female ◽  
Follicular Growth ◽  
Preantral Follicles ◽  
Differentiation Factor ◽  
Growth Differentiation Factor 9

Abstract FSH regulates follicular growth in a stage-development fashion. Although preantral follicle stage is gonadotropin responsive, FSH is not required for preantral follicular growth. With the antrum, the follicles continue growing under the influence of FSH and become gonadotropin dependent. Although thyroid hormone is important for normal female reproductive function, its role and interaction with FSH in the regulation of preantral ovarian follicular growth is yet to be defined. In the present study, we have examined the action and interaction of FSH and T3 in the regulation of the growth of preantral follicles, especially in their transition from preantral to early antral stage, using an established follicle culture system and evaluated the involvement of growth differentiation factor-9 (GDF-9) in this process in vitro. We have demonstrated that although T3 alone had no effect on follicular development, it markedly enhanced FSH-induced preantral follicular growth. Although FSH alone significantly down-regulated FSH receptor (FSHR) mRNA abundance in the preantral follicles and T3 alone was ineffective, expression of the message was significantly increased in the presence of both hormones. In addition, intra-oocyte injection of GDF-9 antisense oligonucleotides (GDF-9 morpholino) induced follicular cell apoptosis and suppressed follicular growth induced by FSH and T3. These responses were attenuated by exogenous GDF-9. Our findings support the concept that thyroid hormone regulates ovarian follicular development through its direct action on the ovary and that promotes FSH-induced preantral follicular growth through up-regulation of FSHR, a mechanism dependent on the expression and action of oocyte-derived GDF-9.

scholarly journals The Role of Androgens in Mammals Folliculogenesis

2018 ◽  
Vol 44 (1) ◽  
pp. 15
Author(s):  
Livia Brunetti Apolloni ◽  
Jamily Bezerra Bruno ◽  
Benner Geraldo Alves ◽  
José Ricardo de Figueiredo
Keyword(s):  
Androgen Receptor ◽  
In Vitro Culture ◽  
Steroid Hormones ◽  
Oocyte Maturation ◽  
Follicular Development ◽  
Follicular Growth ◽  
Preantral Follicles ◽  
Ovarian Cells

Introduction: Steroid hormones production is a physiological process termed steroidogenesis. An important stage of this process is the conversion of androgens into estrogens through aromatase enzyme. Furthermore, androgens are important in the process of folliculogenesis, promoting follicular growth in different species. Thus, the aim of this review was to present the process of synthesis, mechanism of action, and importance of androgens in folliculogenesis. Additionally, the main results of in vitro culture of ovarian cells in the presence of these hormones were emphasized.Review: Folliculogenesis begins in prenatal life in most of species and can be defined as the process of formation, follicular growth, and oocyte maturation. Preantral follicles represent 95% of the follicular population and assisted reproductive technologies have been developed (e.g., Manipulation of Oocytes Enclosed in Preantral Follicles - MOEPF) in order to avoid the great follicle loss that occurs naturally in vivo by atresia. The MOEPF aim to obtain a large number of competent oocytes from preantral follicles and then subject to in vitro maturation, fertilization, and culture for embryo production. However, the development of an efficient medium to ensure the follicular survival and oocyte maturation is the major challenge of this biotechnology. To achieve the success on in vitro culture, the effects of substances as androgens on follicular development have been evaluated. Androgens are steroid hormones produced in theca cells (TC) that are fundamental for follicular growth. These cells provide all the androgens required by the developing follicles for conversion into estrogens by the granulosa cells (GC). Androgens receptors (AR) are localized in cell cytoplasm of all follicular categories, being more expressed in preantral follicles. The androgen pathway initiates through its connection to its receptor, making a complex androgen-AR, that in the nucleus helps on the process of gene transcription related with follicular survival. This mechanism is androgen receptor genomic activity. In addition to genomic action, there is an androgen receptor non-genomic activity. This occurs through activation of AR and its interaction with different signaling molecules located on the cell membrane, triggering events that aid in the follicular development. Regardless of the androgens actions, ovarian cells of several species subjected to in vitro culture have shown the importance of these hormones on the follicle development. Recent studies demonstrated that androgens addition on the culture medium stimulated the activation of preantral follicles (bovine and caprine), antrum formation (swine), survival (non-primate), and oocyte maturation (antral follicles; bovine). Also, some studies suggest that the addition of these hormones on in vitro culture is dose-dependent and species-specific.Conclusion: This review shows the role of androgens in different stages of follicular development and its action as a substrate for steroidogenesis and transcription of genes related to follicular survival and oocyte maturation. However, when these hormones should be added during in vitro follicular culture and which concentration is required remains unclear, being necessary more studies to elucidate these aspects.

Influence of follicle-stimulating hormone concentrations on the integrity and development of bovine follicles cultured in vitro

Zygote ◽  
2018 ◽  
Vol 26 (5) ◽  
pp. 417-423 ◽  
Author(s):  
C. Bizarro-Silva ◽  
M.M. Santos ◽  
J.R. Gerez ◽  
S.M. González ◽  
L.A. Lisboa ◽  
...  
Keyword(s):  
Ovarian Tissue ◽  
Follicle Stimulating Hormone ◽  
Follicular Development ◽  
Follicular Growth ◽  
Minimal Essential Medium ◽  
Preantral Follicles ◽  
Mean Diameter ◽  
Stimulating Hormone

SummaryThis study investigated the in vitro culture of bovine follicles included in ovarian tissue for 2 or 6 days (D2 or D6), with the addition of different concentrations of follicle-stimulating hormone (FSH) (0, 10, 50, 100 or 200 ng/ml). Data were compared for follicular development, morphological integrity and diameter of follicles and oocytes. Ovaries (n = 10) from Nelore cows (n = 5) were divided into fragments (n = 11 per ovary) and were immediately fixed in Bouin’s solution (D0) or were individually cultured for 2 or 6 days in one of the described concentrations of FSH and then processed for histology. Compared with the rates of follicular development at D2 for minimal essential medium (MEM) (75.0%) and 50 ng/ml of FSH (71.1%), the best rates of follicular development at D2 were obtained with 10 (84.7%), 100 (87.5%) and 200 ng/ml of FSH (85.0%; P<0.05). After 6 days of cultivation, there were no differences among treatments regarding follicular growth. The morphological integrity of preantral follicles was better maintained by 100 ng/ml FSH for 2 and 6 days of cultivation (51.2 and 40.4%, respectively; P<0.05) than that for MEM (D2: 30.9%, D6: 20.8%), 10 (D2: 39.2%, D6: 22.8%), 50 (D2: 30.4%, D6: 28.8%) and 200 ng/ml FSH (D2: 45.2%, D6: 36.8%). FSH at 100 ng/ml provided the highest mean diameter averages: 34.5±10.8 µm at D2 and 33.2±12.5 µm at D6 (P<0.05). We concluded that the medium supplemented with 100 ng/ml FSH during in vitro culture provided appropriate conditions for the development and morphological integrity of preantral follicles in cattle.

Effect of growth differentiation factor 9 (GDF-9) on in vitro development of collared peccary preantral follicles in ovarian tissues

2021 ◽  
Vol 226 ◽  
pp. 106717
Author(s):  
Lívia B. Campos ◽  
Andreia M. Silva ◽  
Érica C.G. Praxedes ◽  
Luana G.P. Bezerra ◽  
Jeferson L.S. Freitas ◽  
...  
Keyword(s):  
In Vitro Development ◽  
Preantral Follicles ◽  
Differentiation Factor ◽  
Growth Differentiation Factor 9 ◽  
Collared Peccary ◽  
Vitro Development

Regulatory Mechanism of Rat Preantral Follicular Development: Involvement of FSH, Thyroid Hormone and Growth Differentiation Factor-9.

2008 ◽  
Vol 78 (Suppl_1) ◽  
pp. 73-73
Author(s):  
Noriko Kobayashi ◽  
Makoto Orisaka ◽  
Noriaki Sakuragi ◽  
Fumikazu Kotsuji ◽  
Arthur Leader ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Regulatory Mechanism ◽  
Follicular Development ◽  
Differentiation Factor ◽  
Growth Differentiation Factor 9

Dynamic medium containing growth differentiation factor-9 and FSH maintains survival and promotes in vitro growth of caprine preantral follicles after long-term in vitro culture

2013 ◽  
Vol 25 (6) ◽  
pp. 955 ◽  
Author(s):  
A. M. C. V. Alves ◽  
R. N. Chaves ◽  
R. M. P. Rocha ◽  
L. F. Lima ◽  
P. M. Andrade ◽  
...  
Keyword(s):  
In Vitro Culture ◽  
Culture Period ◽  
Oocyte Diameter ◽  
Primordial Follicles ◽  
Preantral Follicles ◽  
Differentiation Factor ◽  
Follicle Diameter ◽  
Growth Differentiation Factor 9

The aim of the present study was to evaluate the effects of growth differentiation factor 9 (GDF-9) and FSH on the in vitro development of caprine preantral follicles cultured for 16 days. Ovarian fragments were cultured in αMEM+ (α-minimum essential medium, pH 7.2–7.4, 10 μg mL–1 insulin, 5.5 μg mL–1 transferrin, 5.0 ng mL–1 selenium, 2 mM glutamine, 2 mM hypoxanthine and 1.25 mg mL–1 bovine serum albumin) in the absence or presence of 200 ng mL–1 GDF-9 and/or 50 ng mL–1 FSH added during the first (Days 0–8) and/or second (Days 8–16) half of the culture period. Non-cultured and cultured fragments were processed for histological and ultrastructural analyses. After 16 days, all treatments using GDF-9 or FSH showed higher rates of follicular survival compared with αMEM+ alone. Compared with non-cultured control, sequential culture media containing GDF-9 and/or FSH significantly increased the percentage of developing follicles and follicle diameter. Moreover, a progressive increase in oocyte diameter was observed only with sequential culture medium containing GDF-9 until Day 8 followed by FSH (GDF-9/FSH) in the second half of the culture period. After 16 days of culture, ultrastructural analysis confirmed the integrity of follicles cultured in the presence of GDF-9/FSH. In conclusion, a dynamic medium containing GDF-9 and FSH (GDF-9/FSH) maintained follicular integrity and promoted activation of primordial follicles and growth during long-term in vitro culture of goat preantral follicles.

scholarly journals Growth Differentiation Factor 9 Promotes Rat Preantral Follicle Growth by Up-Regulating Follicular Androgen Biosynthesis

Endocrinology ◽  
2009 ◽  
Vol 150 (6) ◽  
pp. 2740-2748 ◽  
Author(s):  
Makoto Orisaka ◽  
Jin-Yi Jiang ◽  
Sanae Orisaka ◽  
Fumikazu Kotsuji ◽  
Benjamin K. Tsang
Keyword(s):  
Cell Communication ◽  
Follicular Development ◽  
Preantral Follicle ◽  
Follicle Growth ◽  
Androgen Receptor Antagonist ◽  
Differentiation Factor ◽  
Growth Differentiation Factor 9 ◽  
Antisense Oligos

The transition from preantral to early antral stage is the penultimate stage of ovarian follicular development in terms of gonadotropin dependence and follicle destiny. Although oocyte-somatic cell communication is important in early follicular development, our knowledge of the precise role of the oocyte-derived growth differentiation factor (GDF)-9 during preantral follicle growth is incomplete. We examined whether and by what means oocyte-derived GDF-9 controls follicular development and steroidogenesis during the preantral to early antral transition, by a combination of in vitro gene manipulation (i.e. intraoocyte injection of GDF-9 antisense oligos) and preantral follicle culture. Intraoocyte injection of GDF-9 antisense suppressed rat preantral follicle growth in vitro, whereas GDF-9 enhanced follicular development. GDF-9 augmented testosterone production in preantral follicles. GDF-9 antisense suppressed androgen production and CYP17A1 mRNA expression in cultured follicles, a response attenuated by exogenous GDF-9. The nonaromatizable androgen 5α-dihydrotestosterone rescued the follicular growth arrest caused by GDF-9 down-regulation. The specific androgen receptor antagonist flutamide suppressed GDF-9-induced preantral follicle growth in vitro. The data suggest that GDF-9 plays an important role in promoting preantral follicle growth by up-regulating follicular androgen biosynthesis. GDF-9 is essential for CYP17A1 expression during follicular development from the preantral to the early antral stage.

scholarly journals Hesperidin improves the follicular development in 3D culture of isolated preantral ovarian follicles of mice

2019 ◽  
Vol 244 (5) ◽  
pp. 352-361 ◽  
Author(s):  
Hamed Shoorei ◽  
Majid Banimohammad ◽  
Maziar M Kebria ◽  
Mohammad Afshar ◽  
Mohammad MH Taheri ◽  
...  
Keyword(s):  
In Vitro Fertilization ◽  
Mrna Expression ◽  
Embryo Development ◽  
3D Culture ◽  
Follicular Development ◽  
Follicular Growth ◽  
Vitro Fertilization ◽  
Preantral Follicles ◽  
Mrna Expression Levels

In vitro follicular culture systems provide optimal culture models for research about the physiology of the ovary and support the clinical practices to achieve competent mature oocytes for in vitro fertilization. In vitro maturation of preantral follicles makes it possible to study the effects of therapeutic agents on various conditions or disorders of the ovary. Nowadays, preventive bioflavonoids against cancer, hypercholesterolemia, fatty liver, or a variety of toxic agents are in focus. The aim of this study was to design and investigate the impacts of different concentrations of hesperidin, a glycoside flavonoid, on the in vitro preantral follicle growth and maturation in the three-dimensional (3D) culture system which was made with sodium alginate. Preantral follicles (n = 1363) were mechanically isolated from immature mice ovaries, then, after capsulating, they were randomly divided into four groups: the control group received no concentration of hesperidin, and three experimental groups were supplemented with 10, 22.5, and 50 µmol/L of hesperidin. All groups were cultured for 12 days. At the end of the culture period, the percentage of survival rate, antrum formation, obtained metaphase II oocytes, and the secretion of 17β-estradiol and progesterone were significantly higher in the group Hesp 50 (50 µmol/L hesperidin). Moreover, the mean average of follicular diameter cultured in the group Hesp 50 was also increased and the mRNA expression levels of PCNA, FSH-R, and Bcl-2 genes were higher, while Bax mRNA expression was significantly reduced compared with the other groups. Follicles cultured in the presence of 50 µmol/L of hesperidin had a higher fertilization rate and embryo development. Adding hesperidin at the concentration of 50 µmol/L to the culture medium resulted in higher follicular growth and maturation and increased the rate of in vitro fertilization and embryo development. Impact statement It has been stated that hesperidin has many pharmacological effects, such as anti-inflammatory and antioxidant effects, antimicrobial activity, and anti-carcinogenic activity; but hesperidin and its derivatives have been under investigation as anti-fertility factors for a very long time. However, our results show that hesperidin can improve mice follicular growth and maturation during in vitro 3D culture. Hesperidin as an antioxidant factor could enhance the mRNA expression levels of two important genes involved in folliculogenesis, PCNA, and FSH-R. Our results prove for the first time that hesperidin not only has deleterious effects on follicular development but can also increase rates of in vitro fertilization and embryo development.

scholarly journals Effects of IGF-I bioavailability on bovine preantral follicular development in vitro

Reproduction ◽  
2007 ◽  
Vol 133 (6) ◽  
pp. 1121-1128 ◽  
Author(s):  
Fiona H Thomas ◽  
Bruce K Campbell ◽  
David G Armstrong ◽  
Evelyn E Telfer
Keyword(s):  
Follicular Development ◽  
Follicle Development ◽  
Dependent Manner ◽  
Igf Binding Proteins ◽  
Preantral Follicles ◽  
Follicle Diameter ◽  
Igf I ◽  
Igf Binding ◽  
Development In Vitro

The aim of this study was to determine the effect of regulation of IGF-I bioavailability on preantral follicle development in vitro. Bovine preantral follicles were cultured for 6 days in serum-free medium with increasing doses of Long R3 (LR3) IGF-I (an analog with low affinity for IGF-binding proteins (IGFBPs)), or human recombinant IGF-I (hrIGF-I). Follicle diameter and estradiol production were measured every second day. On day 6, ratios of oocyte/follicle diameter and oocyte morphology were assessed by histological examination, and IGFBP-2 and -3 were detected by immunocytochemistry and in situ hybridization respectively. Both types of IGF-I increased follicle diameter in a dose-dependent manner (P < 0.05) and increased estradiol production over control levels (P < 0.05). However, follicles treated with LR3 IGF-I and the highest concentration of hrIGF-I (1000 ng/ml) had smaller oocyte/follicle ratios, and increased oocyte degeneration, compared with controls or follicles treated with physiological concentrations of hrIGF-I (P < 0.05). IGFBPs were detected in cultured preantral follicles, indicating a requirement for regulation of IGF bioavailability during the early stages of follicular development. Specifically, IGFBP-3 mRNA was found to be expressed in oocytes, and IGFBP-2 immunoreactivity was detected in oocytes and granulosa cells of cultured follicles. In summary, the regulation of IGF-I bioavailability by IGFBPs is necessary for the co-ordination of oocyte and follicle development in vitro.

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