scholarly journals Determine the Role of FSH Receptor Binding Inhibitor in Regulating Ovarian Follicles Development and Expression of FSHR and ERα in Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Luju Lai ◽  
Xiaoyun Shen ◽  
Haoqin Liang ◽  
Yingying Deng ◽  
Zhuandi Gong ◽  
...  
Keyword(s):  
Follicular Development ◽  
Transverse Diameter ◽  
Follicle Development ◽  
Fsh Receptor ◽  
Serum Concentrations ◽  
Primordial Follicles ◽  
Protein Levels ◽  
Ovarian Cortex ◽  
Longitudinal Diameter

Mice of FRBI-1, FRBI-2, and FRBI-3 groups were intramuscularly injected with 20, 30, and 40mg/kg, respectively, for five consecutive days. Ovarian weights of three FRBI groups were reduced in comparison with FSH group. Ovarian cortex thicknesses (OCT) of the FRBI-3 group were less than that of the FSH group (P<0.05). As compared to FSH group, there were fewer numbers of secondary follicles (SFs) and mature follicles (MF) on the ovaries of FRBI-treated mice numbers of primary follicles (PFs) and SFs also decreased. In FRBI-3 mice, we found that the primordial follicles (POF) were scarcer, the follicles developed poorly, and granulosa cells became apoptosis. SF numbers of FRBI-2 and FRBI-3 groups were less than that of the FSH group on day 20 (P<0.05). Maximum longitudinal diameter (MLD) and transverse diameter (MTD) of three FRBI groups became decreased during the experiment. MLD and MTD of the FRBI-3 group were smaller than FSH group. Levels of FSHR mRNA and protein were less than that of CG and FSH group (P<0.05). ERα protein levels of FRBI group and serum concentrations of FSH and estradiol (E2) in the FRBI-treated mice were decreased when compared to CG and FSH group. In conclusion, FSH treatment could increase the numbers of SF and MF, enhance follicle development, reduce the numbers of SF and MF, and depress the follicular development of mice. Furthermore, FRBI declined the mRNA and protein levels of ERα and FSHR in the ovaries and dropped serum concentrations of FSH and E2 of mice.

509. REGULATING MURINE FOLLICLE DEVELOPMENT BY STIMULATION OF THE JAK2/STAT3 SIGNAL TRANSDUCTION PATHWAY

2009 ◽  
Vol 21 (9) ◽  
pp. 108
Author(s):  
R. A. Keightley ◽  
B. Nixon ◽  
S. D. Roman ◽  
D. L. Russell ◽  
R. L. Robker ◽  
...  
Keyword(s):  
Significant Role ◽  
Granulosa Cells ◽  
Ovarian Follicle ◽  
Expression Patterns ◽  
Follicular Development ◽  
Janus Kinase ◽  
Follicle Development ◽  
Mrna Levels ◽  
Primordial Follicles ◽  
Stat3 Signalling

Follicular development requires the recruitment of primordial follicles into the growing follicle pool following initiation of multiple cytokine signalling pathways. Suppression of follicular development is thought to be key to maintaining the population of primordial follicles and allowing for controlled release of these follicles throughout the reproductive lifespan of the female. However, little is known of the processes and signalling molecules that suppress primordial follicle activation and early follicle growth. Our group has identified significant upregulation of the Janus Kinase 2 (JAK2)/ Signal Transducer and Activator of Transcription 3 (STAT3) signalling pathway inhibitor the Suppressor of Cytokine Signalling 4 (SOCS4) that coincides with the initial wave of follicular activation in theneonatal mouse ovary. Further studies by our group have localised the SOCS4 protein to the granulosa cells of activating and growing follicles, suggesting SOCS4 expression may be linked to follicular activation. We have focused on examining protein localisation and gene expression patterns of the eight SOCS family members CIS and SOCS1-7. We have recently demonstrated that co-culture of neonatal ovaries with Kit Ligand (KL) for 2 days increases the mRNA levels of all SOCS genes. We also demonstrated the co-localisation of SOCS2 proteins with the KL receptor c-kit in the mural granulosa cells of antral, and large pre-antral follicles suggesting a significant role for SOCS2 in the later stages of follicular development. We have also shown that culturing ovaries with the potent JAK2 inhibitor AG490 substantially reduces mRNA levels of all SOCS and STAT genes that we have so far measured. We hypothesise a significant role for JAK2/STAT3 signalling in promoting the activation and early growth of ovarian follicles. Our investigations have identified significant roles for JAK2/STAT3 and the SOCS family in the regulation of ovarian follicle development.

Effects of systemic administration or intrabursal injection of serotonin on puberty, first ovulation and follicular development in rats

2013 ◽  
Vol 25 (8) ◽  
pp. 1105 ◽  
Author(s):  
M. J. Moran ◽  
M. E. Ayala ◽  
E. Gallegos ◽  
J. Romero ◽  
R. Chavira ◽  
...  
Keyword(s):  
Serum Concentration ◽  
Follicular Development ◽  
Systemic Administration ◽  
Female Rats ◽  
Subcutaneous Route ◽  
Vaginal Opening ◽  
Serum Concentrations ◽  
Neuroendocrine Mechanism

To elucidate the role of serotonin in the onset of puberty, the effects of both systemic and in-ovarian bursa administration of serotonin on the neuroendocrine mechanism that modulates the onset of puberty, follicular development and first ovulation were evaluated. Two experiments were carried out. For the first, 25 or 37.5 mg kg–1 of bodyweight of serotonin creatinine sulfate was administered by a subcutaneous route to 30-day-old female rats. In the second experiment, serotonin creatinine sulfate was administered directly into the ovarian bursa of 34-day-old female rats. Systemic administration of 25 or 37.5 mg kg–1 of serotonin creatinine sulfate induced a delay in the ages of vaginal opening and first vaginal oestrus, a decrease in the number of ovulating animals, and serum concentrations of FSH, LH, oestradiol and progesterone. An increase in the number of Class 3 (>500 μm) and atretic follicles was observed in the ovaries of these animals. The administration of serotonin creatinine sulfate in the ovarian bursa did not modify the onset of puberty and ovulation, but a reduced serum concentration of oestradiol was observed. Our results suggest that serotonin acts on the components of the hypothalamus–hypophysis–ovary axis by modulating follicular development, ovarian functions and the onset of puberty.

scholarly journals PI3K/PTEN/Akt and TSC/mTOR signaling pathways, ovarian dysfunction, and infertility: an update

2014 ◽  
Vol 53 (3) ◽  
pp. R103-R118 ◽  
Author(s):  
Annu Makker ◽  
Madhu Mati Goel ◽  
Abbas Ali Mahdi
Keyword(s):  
Signaling Pathways ◽  
Ovarian Function ◽  
Follicular Development ◽  
Mtor Signaling ◽  
Ovarian Dysfunction ◽  
Primordial Follicles ◽  
Current State ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation

Abnormalities in ovarian function, including defective oogenesis and folliculogenesis, represent a key female reproductive deficiency. Accumulating evidence in the literature has shown that the PI3K/PTEN/Akt and TSC/mTOR signaling pathways are critical regulators of ovarian function including quiescence, activation, and survival of primordial follicles, granulosa cell proliferation and differentiation, and meiotic maturation of oocytes. Dysregulation of these signaling pathways may contribute to infertility caused by impaired follicular development, intrafollicular oocyte development, and ovulation. This article reviews the current state of knowledge of the functional role of the PI3K/PTEN/Akt and TSC/mTOR pathways during mammalian oogenesis and folliculogenesis and their association with female infertility.

scholarly journals Influence of donor age on development of gonadal tissue from pouch young of the tammar wallaby, Macropus eugenii, after cryopreservation and xenografting into mice

Reproduction ◽  
2002 ◽  
pp. 143-153 ◽  
Author(s):  
D Mattiske ◽  
G Shaw ◽  
JM Shaw
Keyword(s):  
Reproductive Tract ◽  
Follicular Development ◽  
Tammar Wallaby ◽  
Corpora Lutea ◽  
Follicle Development ◽  
Primordial Follicles ◽  
Antral Follicles ◽  
Macropus Eugenii ◽  
Reduced Rate ◽  
Timing Of Onset

Ovaries from a marsupial, the tammar wallaby (Macropus eugenii), were grafted into a eutherian recipient at known stages of development to ascertain whether normal development would occur. Xenografted ovaries from pouch young < 20 days old, before the onset of meiosis, retained few germ cells and developed tubule-like structures reminiscent of seminiferous cords. Ovaries from 50-day-old pouch young, which contain primordial follicles, developed into antral follicles and corpora lutea within the eutherian host, and produced hormones that stimulated the reproductive tract of the host. The timing of onset of antrum formation and the progress of follicle development were advanced relative to the timing of events in ovaries in situ. Frozen-thawed ovaries from 50-day-old donors developed into preantral follicles, but at a reduced rate and number. This finding shows that gonads of a marsupial species can develop as xenografts in a eutherian, forming large antral follicles. Accelerated follicular development in xenografts provides a potentially valuable model for studying the factors that control follicle development. Assisted reproduction of endangered marsupials may also be feasible using follicles from pouch young grown as xenografts in a eutherian host.

scholarly journals Physiological and Pathological Androgen Actions in the Ovary

Endocrinology ◽  
2019 ◽  
Vol 160 (5) ◽  
pp. 1166-1174 ◽  
Author(s):  
Olga Astapova ◽  
Briaunna M N Minor ◽  
Stephen R Hammes
Keyword(s):  
Granulosa Cells ◽  
Polycystic Ovary ◽  
Follicular Development ◽  
Follicle Development ◽  
Female Reproduction ◽  
Negative Effects ◽  
Androgen Excess ◽  
Male Sex ◽  
Androgen Effects

Abstract Androgens, although traditionally thought to be male sex steroids, play important roles in female reproduction, both in healthy and pathological states. This mini-review focuses on recent advances in our knowledge of the role of androgens in the ovary. Androgen receptor (AR) is expressed in oocytes, granulosa cells, and theca cells, and is temporally regulated during follicular development. Mouse knockout studies have shown that AR expression in granulosa cells is critical for normal follicular development and subsequent ovulation. In addition, androgens are involved in regulating dynamic changes in ovarian steroidogenesis that are critical for normal cycling. Androgen effects on follicle development have been incorporated into clinical practice in women with diminished ovarian reserve, albeit with limited success in available literature. At the other extreme, androgen excess leads to disordered follicle development and anovulatory infertility known as polycystic ovary syndrome (PCOS), with studies suggesting that theca cell AR may mediate many of these negative effects. Finally, both prenatal and postnatal animal models of androgen excess have been developed and are being used to study the pathophysiology of PCOS both within the ovary and with regard to overall metabolic health. Taken together, current scientific consensus is that a careful balance of androgen activity in the ovary is necessary for reproductive health in women.

scholarly journals Nitric oxide in follicle development and oocyte competence

Reproduction ◽  
2015 ◽  
Vol 150 (1) ◽  
pp. R1-R9 ◽  
Author(s):  
Giuseppina Basini ◽  
Francesca Grasselli
Keyword(s):  
Nitric Oxide ◽  
Follicular Development ◽  
Reproductive Organs ◽  
Follicle Development ◽  
Oocyte Competence ◽  
Positive Effects ◽  
Ovarian Cells ◽  
Dual Action ◽  
Generating System

Apart from its well-known role in regulating endothelial function, in mammals, nitric oxide (NO) is an important signaling molecule involved in many processes, regulating different biological functions. It has been demonstrated that NO plays a role in the physiology of the reproductive system, where it acts in controlling the activity of reproductive organs in both sexes. In the female of several animal species, experimental data suggest the presence of an intraovarian NO-generating system, which could be involved in the control of follicular development. The role of NO in regulating follicular atresia by apoptosis is still controversial, as a dual action depending mostly on its concentration has been documented. NO also displays positive effects on follicle development and selection related to angiogenic events and it could also play a modulatory role in steroidogenesis in ovarian cells. Both in monovulatory and poliovulatory species, the increase in PGE2production induced by NO via a stimulatory effect on COX-2 activity appears to be a common ovulatory mechanism. Considerable evidence also exists to support an involvement of the NO/NO synthase system in the control of meiotic maturation of cumulus–oocyte complexes.

scholarly journals ATR function is indispensable to allow proper mammalian follicle development

2018 ◽  
Author(s):  
Sarai Pacheco ◽  
Montserrat Garcia-Caldés ◽  
Ignasi Roig
Keyword(s):  
Follicular Development ◽  
Female Fertility ◽  
Follicle Development ◽  
Wild Type ◽  
Hypomorphic Mutation ◽  
Ovarian Cells ◽  
Anti Cancer ◽  
Mammalian Female ◽  
Atr Kinase

AbstractMammalian female fertility relies on the proper development of follicles. Right after birth in mouse, oocytes associate with somatic ovarian cells to form follicles. These follicles grow during adult lifetime to produce viable gametes. In this study, we analyzed the role of the ATM and rad3-related (ATR) kinase in mouse oogenesis and folliculogenesis using a hypomorphic mutation of the Atr gene (Murga et al., 2009). Female mice homozygote for this allele have been reported to be sterile. Our data show that female meiotic prophase is not grossly altered when ATR levels are reduced. However, follicle development is majorly compromised since Atr mutant ovaries present a decrease of growing follicles. Comprehensive analysis of follicular cell death and proliferation suggest that wild-type levels of ATR are required to achieve optimal follicular development. Altogether, these findings suggest that reduced ATR expression causes sterility due to defects in follicular progression rather than in meiotic recombination. We discuss the implication of these findings for the use of ATR inhibitors as anti-cancer drugs and its possible side effects on female fertility.

scholarly journals Effects of reduction of the number of primordial follicles on follicular development to achieve puberty in female rats

Reproduction ◽  
2003 ◽  
pp. 85-94 ◽  
Author(s):  
M Shirota ◽  
S Soda ◽  
C Katoh ◽  
S Asai ◽  
M Sato ◽  
...  
Keyword(s):  
Corn Oil ◽  
Follicular Development ◽  
Primary Phase ◽  
Female Rats ◽  
Female Rat ◽  
Serum Concentrations ◽  
Immature Female ◽  
Primordial Follicles ◽  
Preantral Follicles ◽  
Rat Offspring

Effects of reduction of the number of primordial follicles on follicular development and concentrations of circulating hormones were examined in immature female rat offspring of dams given busulfan intraperitoneally on day 14 of gestation. The offspring of dams treated with 5 mg busulfan kg(-1) showed vaginal opening at an age comparable with the offspring of dams treated with 2.5 mg busulfan kg(-1) or with corn oil as a control, although they exhibited an irregular oestrous cycle until week 14 after birth. The serum concentrations of immunoreactive inhibin and FSH on day 26 after birth of the offspring treated with 5 mg busulfan kg(-1) were similar to those of age-matched controls. On day 15 after birth, however, the concentration of their immunoreactive inhibin was markedly lower than that of controls, whereas the concentration of their FSH was increased inversely. Comparison of the numbers of ovarian follicles in the controls and groups treated with 2.5 mg busulfan kg(-1) and 5 mg busulfan kg(-1) revealed that prenatal treatment with busulfan reduced the number of follicles in the primordial or primary phase and in the preantral phase on day 7 after birth. Although the increase of the ratio of the number of preantral follicles during days 7-13 after birth tended to vary with the prenatal dose of busulfan, the number of preantral follicles in the group treated with 5 mg busulfan kg(-1) was still smaller than in the controls. The concentration of serum immunoreactive inhibin of the offspring treated with busulfan was reduced on day 7 after birth without alteration of the concentration of gonadotrophin. On day 13 after birth, the concentration of serum immunoreactive inhibin was reduced only in the offspring treated with 5 mg busulfan kg(-1), and the concentration of serum FSH of the offspring was increased inversely as found on day 15 after birth. These results indicate that a reduction in the number of primordial follicles decreases the number of follicles that enter the growing phase, a major source of circulating inhibin in the neonatal and infantile ovary, and that consequently increased circulating FSH may accelerate follicular development to achieve puberty.

scholarly journals Macrophage Migration Inhibitory Factor Interacting with Th17 Cells May Be Involved in the Pathogenesis of Autoimmune Damage in Hashimoto’s Thyroiditis

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Haibo Xue ◽  
Yuhua Yang ◽  
Ying Zhang ◽  
Shoujun Song ◽  
Li Zhang ◽  
...  
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Th17 Cells ◽  
Macrophage Migration Inhibitory Factor ◽  
Hashimoto's Thyroiditis ◽  
Overt Hypothyroidism ◽  
Serum Concentrations ◽  
Rt Pcr ◽  
Protein Levels ◽  
Interleukin 17A

Purpose. To explore the possible role of MIF and Th17 cells in the thyroid-specific autoimmune damage of Hashimoto’s thyroiditis (HT).Material and Methods. We enrolled 40 HT patients and 30 healthy controls and divided HT patients into euthyroid subset (n=22) and subclinical or overt hypothyroidism subset (n=18). The percentages of Th17 cells and expressions of MIF, interleukin 17A (IL-17A) mRNA in PBMCs, as well as serum concentrations of MIF, and IL-17A, and thyroid functions, and thyroid-specific autoantibodies (TPOAb, TgAb) were detected by flow cytometry, real-time RT-PCR, ELISA, and ECLIA in all subjects.Results. MIF mRNA, IL-17A mRNA expressions and Th17 cells percentages, serum MIF, and IL-17A protein levels were all significantly higher in HT patients, even in euthyroid subgroup. Additionally, the differences became more obvious in dysfunction subgroup. Importantly, both MIF levels and Th17 cells percentage were positively correlated with serum TPOAb, TgAb, and thyrotropin (TSH) levels in HT patients.Conclusions. These data suggest that MIF and Th17 cells increased dynamically and positively correlated with the markers of thyroid autoimmune damage, which indicated that interaction between MIF and Th17 cells may participate in the pathogenesis and development of thyroid-specific autoimmunity in HT.

scholarly journals FSHR and LHR Expression and Signaling as Well as Maturation and Apoptosis of Cumulus-Oocyte Complexes Following Treatment with FSH Receptor Binding Inhibitor in Sheep

2017 ◽  
Vol 43 (2) ◽  
pp. 660-669 ◽  
Author(s):  
Suocheng Wei ◽  
Xiaoyun Shen ◽  
Zhuandi Gong ◽  
Yingying Deng ◽  
Luju Lai ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Caspase 3 ◽  
Follicular Development ◽  
Control Group ◽  
Fsh Receptor ◽  
Treatment Groups ◽  
Apoptosis Rate ◽  
Protein Levels ◽  
Maturation Rate

Background/Aims: Currently, it remains unknown whether FSH receptor binding inhibitor (FRBI) influences follicular development and reproduction functions in humans and animals. The present study aimed to investigate FRBI effects on in vitro maturation (IVM) and apoptosis of cumulus-oocyte complexes (COCs) of sheep, to determine the effect of FRBI on mRNA and protein levels of FSHR and LHR in COCs, and to elucidate the signal pathway of FRBI effects. Methods: COCs were in vitro cultured for 24h in the IVM media supplemented with varying concentrations of FRBI (0, 10, 20, 30 and 40µg/mL) and FSH (10IU/mL). The harvested COCs were observed under an inverted microscope and maturation rates of COCs were determined. Real time RT-PCR and Western blotting were utilized to detect mRNA and protein levels of FSHR and LHR. The concentrations of FSH, LH and caspase-3 were determined using especial ELISA kits for sheep, respectively. Results: Maturation rates of COCs decreased gradually as FRBI concentrations increased from 0 to 40µg/mL, reaching a bottom value of 23.76% of the FRBI-4 group. The maximal apoptosis rate was detected in the FRBI-4 group. IP3 contents of FRBI-3 and FRBI-4 groups were reduced as compared to control group (CG) and FSH groups (P<0.05). Levels of FSHR protein of FRBI-3 and FRBI-4 groups as well as LHR protein of FRBI-4 group were significantly less than that of CG and FSH group. FSH contents of four FRBI treatment groups were gradually decreased along with the supplementation doses of FRBI. Caspase-3 contents of FRBI groups were reduced with a maximum reduction of the FRBI-2 group. Conclusion: Our results revealed supplement of FRBI into IVM media could dose-dependently decrease the maturation rate and increase apoptosis rate of sheep COCs. A lower dose of FRBI treatment slightly promoted IP3 production, but a higher dose of FRBI reduced IP3 production. FRBI suppressed the mRNA and protein expression levels of FSHR and LHR in sheep COCs. Our study will help to therapy effectively ovarian diseases, improve ovarian and follicular functions, and further to promote fertility of humans and animals.

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