Poor ovarian response to gonadotropin stimulation is associated with low expression of follicle-stimulating hormone receptor in granulosa cells

Cai, Jie; Lou, Hangying; Dong, Minyue; Lu, Xiu-e; Zhu, Yimin; Gao, Huijuan; Huang, He‐Feng

doi:10.1016/j.fertnstert.2006.11.034

Cited by 75 publications

(70 citation statements)

References 27 publications

(34 reference statements)

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“…On the other hand, another study indicated the association of reduced FSHR expression with poor ovarian response in women undergoing IVF. 15 Analysis of the data delineated subjects with A/A genotype at position -29 received higher dose of exogenous FSH for ovulation induction, in comparison with G/G genotype subjects. The results indicate that SNP of the core promoter region at position -29 of FSHR gene may influence sensitivity of the FSHR to FSH in vivo, and that the A/A genotype at position -29 associated with poor ovarian response to FSH, so that subjects with A/A genotype at the -29 positions require higher doses of exogenous FSH for ovulation induction during IVF process.…”

Section: Discussionmentioning

confidence: 99%

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Association of FSH receptor promoter’s polymorphisms with IVF-failure in Iranian women

Bonyadi

Damavandi

Chibine

et al. 2017

Int J Reprod Contracept Obstet Gynecol

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Background: Follicle-Stimulating Hormone Receptor (FSHR) gene shows five Single Nucleotide Polymorphisms (SNPs) in the promoter region at positions -29, -37, - 114, -123 and -138 that have been reported to be associated with higher levels of FSH and various ovarian responses to FSH in IVF (In-vitro fertilization) treatment at different populations. Hence, they are important regulators of hormone activity at the target level in IVF process. This study was performed to investigate the association between FSHR gene polymorphisms and IVF failure in Iranian women.Methods: SNPs in the promoter region of FSHR gene were analyzed by PCR and direct sequencing technique in 90 women in three equally sized groups of IVF failure, IVF success and normal fertile women, using genomic DNA extracted from white blood cells.Results: No significant differences were found in allelic variants frequency and genotype distribution between each category of subjects when analyzing the FSHR SNPs in the promoter region (p-value >0.05). However, analysis of the data revealed that the subjects with A/A genotype at the –29 position received higher amount of exogenous FSH for ovulation induction compared to G/G genotypes.Conclusions: These results indicate that the FSHR SNP at position –29 may influence sensitivity of the FSHR to FSH for ovulation induction in IVF treatment. It may be concluded that the A/A genotype at position –29 is associated with poor ovarian response to FSH so that subjects with A/A genotype at the –29 position may require higher doses of exogenous FSH for ovulation induction during IVF process.

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Section: Discussionmentioning

confidence: 99%

“…1 With a worldwide incidence of [12][13][14][15] percent, infertility is a difficult challenge faced by young couples. In Iran, infertility rate is estimated to be approximately 20-21 percent.…”

Section: Introductionmentioning

confidence: 99%

Association of FSH receptor promoter’s polymorphisms with IVF-failure in Iranian women

Bonyadi

Damavandi

Chibine

et al. 2017

Int J Reprod Contracept Obstet Gynecol

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“…Aliquots of suspended granulosa cells (1!10 6 cells in 100 ml) were immunolabeled using a double-indirect method as previously described (Cai et al 2007, Abir et al 2008. The cells were incubated separately with an optimized concentration of 4 mg/ml affinity purified polyclonal antibody to BMPR1B, FSHR, or LH receptor (LHR) for 25 min at 5 8C (Millennium Science, Surrey Hills, VIC, Australia).…”

Section: Receptorsmentioning

confidence: 99%

“…The antibodies were polyclonal goat anti-BMPR1B (sc-5679), goat anti-FSHR (sc-7798), and goat anti-LHR (sc-26341) (all from Santa Cruz Biotechnology), anti-goat second antibody conjugated with Alexa 488 (Al-Samerria & Almahbobi 2014). In addition, the antibodies have been previously reported in human studies (Haÿ et al 2004, Cai et al 2007, Pidoux et al 2007, Abir et al 2008) and using flow cytometry . Immunolocalization of LHR in human placental trophoblasts demonstrated positive strong staining with human chorionic gonadotropin, and no staining was observed in nonspecific isotypic negative controls (Pidoux et al 2007).…”

Section: Receptorsmentioning

confidence: 99%

Flow cytometric analysis of FSHR, BMRR1B, LHR and apoptosis in granulosa cells and ovulation rate in merino sheep

Regan¹,

McFarlane²,

O’Shea³

et al. 2015

Reproduction

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The aim of the present study was to determine the direct cause of the mutation-induced, increased ovulation rate in Booroola Merino (BB) sheep. Granulosa cells were removed from antral follicles before ovulation and post-ovulation from BB (nZ5) and WT (nZ12) Merino ewes. Direct immunofluorescence measurement of mature cell surface receptors using flow cytometry demonstrated a significant up-regulation of FSH receptor (FSHR), transforming growth factor beta type 1, bone morphogenetic protein receptor (BMPR1B), and LH receptor (LHR) in BB sheep. The increased density of FSHR and LHR provide novel evidence of a mechanism for increasing the number of follicles that are recruited during dominant follicle selection. The compounding increase in receptors with increasing follicle size maintained the multiple follicles and reduced the apoptosis, which contributed to a high ovulation rate in BB sheep. In addition, we report a mutation-independent mechanism of down-regulation to reduce receptor density of the leading dominant follicle in sheep. The suppression of receptor density coincides with the cessation of mitogenic growth and steroidogenic differentiation as part of the luteinization of the follicle. The BB mutation-induced attenuation of BMPR1B signaling led to an increased density of the FSHR and LHR and a concurrent reduction in apoptosis to increase the ovulation rate. The role of BMPs in receptor modulation is implicated in the development of multiple ovulations.Reproduction (2015) 150 151-163

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“…Therefore, this relationship is interesting to examine, especially given knowledge that a decrease in FSHR density has the potential of altering the response of rat granulosa cells to FSH from being stimulatory to antagonistic (Donadeu & Ascoli 2005). Additionally, human IVF patients that present as 'poor responders' to FSH treatment have been shown to have lower ovarian FSHR levels (Cai et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Absence of seasonal changes in FSHR gene expression in the cat cumulus–oocyte complex in vivo and in vitro

Hobbs

Howard²,

Wildt³

et al. 2012

Reproduction

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Domestic cat oocytes are seasonally sensitive to FSH. Compared with those collected during the breeding season, oocytes from the nonbreeding (NB) season require more FSH during in vitro maturation to achieve comparable developmental competence. This study tested the hypothesis that this seasonal variation was due to altered expression of FSH receptors (FSHR) and/or FSH-induced genes. Relative expression levels of FSHR mRNA and FSH-enhanced gene estrogen receptor b (ESR2) were measured by qPCR in whole ovaries and immature cumulus-oocyte complexes (COCs) isolated from cat ovaries during the natural breeding vs NB seasons. Expression levels of FSH-induced genes prostaglandin-endoperoxide synthase 2 (PTGS2), early growth response protein-1 (EGR1), and epidermal growth factor receptor (EGFR) were examined in mature COCs from both seasons that were a) recovered in vivo or b) matured in vitro with conventional (1 mg/ml) or high (10 mg/ml) FSH concentrations. Overall, FSHR mRNA levels were lower in whole ovaries during the NB compared with breeding season but were similar in immature COCs, whereas ESR2 levels did not differ in either group between intervals. We observed changes in PTGS2, EGR1, and EGFR mRNA expression patterns across maturation in COCs within but not between the two seasons. The lack of seasonal differentiation in FSH-related genes was not consistent with the decreased developmental capacity of oocytes fertilized during the NB season. These findings reveal that the seasonal decrease in cat oocyte sensitivity to FSH occurs both in vivo and in vitro. Furthermore, this decline is unrelated to changes in expression of FSHR mRNA or mRNA of FSH-induced genes in COCs from antral follicles.

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Poor ovarian response to gonadotropin stimulation is associated with low expression of follicle-stimulating hormone receptor in granulosa cells

Cited by 75 publications

References 27 publications

Association of FSH receptor promoter’s polymorphisms with IVF-failure in Iranian women

Association of FSH receptor promoter’s polymorphisms with IVF-failure in Iranian women

Flow cytometric analysis of FSHR, BMRR1B, LHR and apoptosis in granulosa cells and ovulation rate in merino sheep

Absence of seasonal changes in FSHR gene expression in the cat cumulus–oocyte complex in vivo and in vitro

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