Granulosa Cell Apoptosis Induced by a Novel FSH Binding Inhibitory Peptide From Human Ovarian Follicular Fluid

Chitnis, Swati S.; Navlakhe, Rajshri M.; Shinde, Gayatri; Barve, Sharmila J.; D’Souza, Serena; Mahale, Smita D.; Nandedkar, Tarala D.

doi:10.1369/jhc.2008.951475

Cited by 16 publications

(17 citation statements)

References 25 publications

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“…These results indicated supplement of FRBI into the IVM medium could dose-dependently reduce the maturation rate and increase apoptosis rate of sheep COCs. Our findings were in agreement with an earlier report [21-23]. …”

Section: Discussionsupporting

confidence: 94%

“…However, FSH-receptor binding inhibitor (FRBI), as an FSH antagonist, influenced the efficacy of FSH by blocking the binding of FSH to FSHR in the presence of FSH [8, 10]. In vivo administration of FRBI resulted in the suppression of ovulation and induced follicular atresia and apoptosis of mice [7, 21] and further impaired the proliferation of granulosa cells. Therefore, FRBI interfered with FSH-FSHR interaction leading to a blockage of FSH action [3].…”

Section: Discussionmentioning

confidence: 99%

“…One non-steroidal low molecular weight factor, FSH receptor binding inhibitor (FRBI), was identified from the follicular fluids of sheep and human [7, 8]. This FRBI, as an FSH antagonist, blocks the binding of hFSH to rat granulosa cells.…”

Section: Introductionmentioning

confidence: 99%

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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

Wei

Shen

Gong

et al. 2017

Cell Physiol Biochem

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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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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

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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

Wei

Shen

Gong

et al. 2017

Cell Physiol Biochem

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“…Follicle‐stimulating hormone receptor‐binding inhibitor‐8 or OP has been shown to induce apoptosis in mice granulosa cells . Hence, it was of interest to further evaluate the effect of FRBI‐8 on the proliferation of granulosa cells.…”

Section: Discussionmentioning

confidence: 99%

Effect of FSH Receptor‐Binding Inhibitor‐8 on FSH‐Mediated Granulosa Cell Signaling and Proliferation

et al. 2013

Self Cite

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Follicle-stimulating hormone is important for mammalian reproduction. It acts through specific receptors located on the plasma membrane of granulosa cells in ovaries and Sertoli cells in testes. The binding of follicle-stimulating hormone to its receptor activates intracytoplasmic signaling pathways leading to steroidogenesis. These steroids in turn regulate the follicle-stimulating hormone action from the anterior pituitary through exerting negative feedback effect. In addition to steroids, non-steroidal factors secreted by the ovaries are believed to modulate follicle-stimulating hormone action through autocrine/paracrine mode. One such low molecular weight peptide referred to as follicle-stimulating hormone receptor-binding inhibitor-8 purified from human follicular fluid has been extensively studied. Follicle-stimulating hormone receptor-binding inhibitor-8 has been shown to inhibit binding of follicle-stimulating hormone to its receptor. The present article describes the effect of follicle-stimulating hormone receptor-binding inhibitor-8 on follicle-stimulating hormone-induced signaling in rat granulosa cells. Follicle-stimulating hormone receptor-binding inhibitor-8 inhibited the follicle-stimulating hormone-induced cAMP, and the effect was observed to be mediated through the protein kinase A. Further, an inhibitory effect of follicle-stimulating hormone receptor-binding inhibitor-8 on the granulosa cell proliferation was evaluated using COV434 cell line which is derived from the human granulosa cell tumor. The effect of the peptide on the cell cycle analysis showed an increase in apoptotic population and the arrest of G1 phase. These findings suggest that follicle-stimulating hormone receptor-binding inhibitor-8 acts as a follicle-stimulating hormone antagonist and affects the follicle-stimulating hormone-mediated signaling and proliferation in the granulosa cells.

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“…Briefly, fresh and cryopreserved immature rat testicular fragments (TUB) were fixed in modified Karnovsky's fixative (30) for 4-6 hours at 4 C, postfixed with osmiumtetraoxide, dehydrated, cleared, infiltrated, and embedded in Araldite as described elsewhere (31).…”

Section: Ultrastructural Studiesmentioning

confidence: 99%

Efficient cryopreservation of testicular tissue: effect of age, sample state, and concentration of cryoprotectant

Unni

Kasiviswanathan

D’Souza

et al. 2012

Fertility and Sterility

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Granulosa Cell Apoptosis Induced by a Novel FSH Binding Inhibitory Peptide From Human Ovarian Follicular Fluid

Cited by 16 publications

References 25 publications

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

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

Effect of FSH Receptor‐Binding Inhibitor‐8 on FSH‐Mediated Granulosa Cell Signaling and Proliferation

Efficient cryopreservation of testicular tissue: effect of age, sample state, and concentration of cryoprotectant

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