Gene Expression Profiles of Human Granulosa Cells Treated With Bioequivalent Doses of Corifollitrophin Alfa or Recombinant Human Follicle-Stimulating Hormone
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PROVIDER: PRJNA476296 | ENA |
REPOSITORIES: ENA
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Project description:Using recombinant DNA technologies, a new chimeric gene containing the coding sequences of the follicle stimulating hormone (FSH) β-subunit and the C-terminal peptide of the human chorionic gonadotrophin (hCG) β-subunit have been designed to generate a new gonadotrophin named corifollitrophin alfa. Corifollitrophin alfa has longer elimination half-life and a slower rate of absorption compared with FSH, which makes corifollitrophin alfa a long-acting hormone employed as a substitute of the recombinant FSH (recFSH) in the controlled ovarian stimulation (COS). The purpose of this study is to compare the gene expression profiles elicited by bioequivalent doses of corifollitrophin alfa or recFSH in primary cultures of human granulosa cells (hGCs). Both gonadotrophins exert their functions by binding FSH receptors (FSHRs), activating signaling pathways that increase the cyclic adenosine monophosphate (cAMP) intracellular content. Bioequivalence has been defined as the dose/duration of gonadotrophin treatment able to promote the same amount of intracellular cAMP. Primary cultured hGCs were treated with different doses of either gonadotrophin and the cAMP was measured after different incubation times to establish the bioequivalence. Results obtained by comparing the bioequivalent treatments, showed that corifollitrophin alfa is more effective than recFSH in inducing aromatase gene expression after 6 and 24 hours from the initial stimulation in agreement with its long-acting characteristic’s.
2020-06-01 | GSE115846 | GEO
Project description:FSH is considered as the most critical regulatory factor for follicle growth and development. It is widely acknowledged that exogenous administration of FSH can effectively stimulate ovulation.However, these techniques have several drawbacks such as high cost and detrimental effects on hormone balance and embryo implantation.Sulforaphane (SFN) is a naturally occurring compound that belongs to the isothiocyanate group, which is predominant in cruciferous vegetables.Our previous research demonstrated SFN could inhibit hypoxia-evoked apoptosis in porcine GCs. Intriguingly, SFN exhibits a biphasic dose-response, stimulating cell growth at low doses in various mammalian cells. Therefore,to investigate the functional implications of sulforaphane in the regulation of granulosa cell proliferation, we conducted a gene expression profiling analysis using RNA-seq data, comparing SFN to follicle stimulating hormone (FSH).
2024-10-01 | GSE233365 | GEO
Project description:To identify the DE mRNA and lncRNA between the recombinant pig follicle-stimulating hormone traetment group and control grooup.
2022-02-21 | GSE192605 | GEO
Project description:PurposeTo determine the pattern of dose adjustment of recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa) during ovarian stimulation (OS) for assisted reproductive technology (ART) in a real-world setting.MethodsThis was an observational, retrospective analysis of data from an electronic de-identified medical records database including 39 clinics in the USA. Women undergoing OS for ART (initiated 2009-2016) with r-hFSH-alfa (Gonal-f® or Gonal-f RFF Redi-ject®) were included. Assessed outcomes were patients' baseline characteristics and dosing characteristics/cycle.ResultsOf 33,962 ART cycles, 13,823 (40.7%) underwent dose adjustments: 23.4% with ≥1 dose increase, 25.4% with ≥1 dose decrease, and 8.1% with ≥1 increase and ≥1 decrease. Patients who received dose adjustments were younger (mean [SD] age 34.8 [4.58] years versus 35.9 [4.60] years, p<0.0001) and had lower BMI (25.1 [5.45] kg/m2 versus 25.5 [5.45] kg/m2, p<0.0001) than those who received a constant dose. The proportion of patients with non-normal ovarian reserve was 38.4% for those receiving dose adjustment versus 51.9% for those with a constant dose. The mean (SD) number of dose changes/cycle was 1.61 (0.92) for cycles with any dose adjustment, 1.72 (1.03) for cycles with ≥1 dose increase, 2.77 (1.00) for cycles with ≥1 dose increase and ≥1 decrease (n=2,755), and 1.88 (1.03) for cycles with ≥1 dose decrease.ConclusionsDose adjustment during OS is common in clinical practice in the USA and occurred more often in younger versus older patients, those with a high versus non-normal ovarian reserve or those with ovulation disorders/polycystic ovary syndrome versus other primary diagnoses of infertility.
| S-EPMC8696034 | biostudies-literature
Project description:BackgroundThis study compared the effectiveness of recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa; GONAL-f®) with urinary highly purified human menopausal gonadotropin (hMG HP; Menogon HP®), during assisted reproductive technology (ART) treatments in Germany.MethodsData were collected from 71 German fertility centres between 01 January 2007 and 31 December 2012, for women undergoing a first stimulation cycle of ART treatment with r-hFSH-alfa or hMG HP. Primary outcomes were live birth, ongoing pregnancy and clinical pregnancy, based on cumulative data (fresh and frozen-thawed embryo transfers), analysed per patient (pP), per complete cycle (pCC) and per first complete cycle (pFC). Secondary outcomes were pregnancy loss (analysed per clinical pregnancy), cancelled cycles (analysed pCC), total drug usage per oocyte retrieved and time-to-live birth (TTLB; per calendar week and per cycle).ResultsTwenty-eight thousand six hundred forty-one women initiated a first treatment cycle (r-hFSH-alfa: 17,725 [61.9%]; hMG HP: 10,916 [38.1%]). After adjustment for confounding variables, treatment with r-hFSH-alfa versus hMG HP was associated with a significantly higher probability of live birth (hazard ratio [HR]-pP [95% confidence interval (CI)]: 1.10 [1.04, 1.16]; HR-pCC [95% CI]: 1.13 [1.08, 1.19]; relative risk [RR]-pFC [95% CI]: 1.09 [1.05, 1.15], ongoing pregnancy (HR-pP [95% CI]: 1.10 [1.04, 1.16]; HR-pCC [95% CI]: 1.13 [1.08, 1.19]; RR-pFC [95% CI]: 1.10 [1.05, 1.15]) and clinical pregnancy (HR-pP [95% CI]: 1.10 [1.05, 1.14]; HR-pCC [95% CI]: 1.14 [1.10, 1.19]; RR-pFC [95% CI]: 1.10 [1.06, 1.14]). Women treated with r-hFSH-alfa versus hMG HP had no statistically significant difference in pregnancy loss (HR [95% CI]: 1.07 [0.98, 1.17], were less likely to have a cycle cancellation (HR [95% CI]: 0.91 [0.84, 0.99]) and had no statistically significant difference in TTLB when measured in weeks (HR [95% CI]: 1.02 [0.97, 1.07]; p = 0.548); however, r-hFSH-alfa was associated with a significantly shorter TTLB when measured in cycles versus hMG HP (HR [95% CI]: 1.07 [1.02, 1.13]; p = 0.003). There was an average of 47% less drug used per oocyte retrieved with r-hFSH-alfa versus hMG HP.ConclusionsThis large (> 28,000 women), real-world study demonstrated significantly higher rates of cumulative live birth, cumulative ongoing pregnancy and cumulative clinical pregnancy with r-hFSH-alfa versus hMG HP.
| S-EPMC8207759 | biostudies-literature
Project description:BackgroundWomen with anovulatory polycystic ovary syndrome (PCOS) are generally insulin-resistant and as a consequence are often treated with the biguanide metformin. Results with metformin have, however, been variable with some studies demonstrating induction of regular cycles and an increase in ovulation, whereas others do not. Hence more understanding is needed regarding the mechanism of metformin's actions in ovarian granulosa cells especially in light of previous demonstrations of direct actions.ObjectiveThe aim of this study was to investigate metformin's interaction with the FSH/cAMP/protein kinase A pathway, which is the primary signaling pathway controlling CYP19A1 (aromatase) expression in the ovary.MethodsThe effect of metformin on FSH and forskolin-stimulated aromatase expression in human granulosa cells was measured by quantitative real-time PCR. Activity was assessed after transfection with a promoter II-luciferase construct, and by an RIA measuring conversion of androgen to estrogens. The effect on FSH receptor (FSHR) mRNA was assessed by quantitative PCR. Levels of phosphorylated cAMP response element binding protein (CREB) and CREB-regulated transcription coactivator 2 (CRTC2) were measured by Western blotting and cAMP by a bioluminescent assay.ResultsMetformin markedly reduced FSH but not forskolin-stimulated aromatase expression and activity. This effect was exerted by inhibition of basal and ligand-induced up-regulation of FSHR expression. Metformin also reduced FSH-induced phosphorylation of CREB and hence CRE activity, which could potentially disrupt the CREB-CREB-binding protein-CRTC2 coactivator complex that binds to CRE in promoter II of the aromatase gene. This is mediated in an AMP-activated protein kinase-independent manner, and does not involve alteration of cAMP levels.ConclusionThese finding have implications for the use of metformin in the treatment of anovulation in women with PCOS.
| S-EPMC3784648 | biostudies-literature
Project description:Interaction proteomics of yeast Sac1-ALFA compared to untagged control strains
2023-12-01 | PXD039849 | Pride
Project description:RNA-Seq in porcine ovaries treated with recombinant pig follicle-stimulating hormone (rpFSH)
| PRJNA792332 | ENA
Project description:YTHDF2 mediates the action of BDNF stimulating proliferation of porcine follicle granulosa cells
| PRJNA1039737 | ENA
Project description:In the normal mouse the pituitary gonadotrophins determine development, maturation and physiological regulation of the testis with follicle-stimulating hormone (FSH) activating the Sertoli cell and luteinising hormone (LH) the Leydig cell. To look at the potential interaction of cell types within the testis following hormone stimulation we have investigated the effect of rFSH on testicular gene expression in the hypogonadal (hpg) male mouse. Due to a deletion in the gene encoding gonadotrophin-releasing hormone (GnRH), FSH and LH levels are at the lower limit of detection in the circulation and mice remain in a pre-pubertal state throughout life unless given exogenous hormone. Here we have addressed important question of changes in the global gene expression profile of testicular tissue following hormone stimulation (rFSH) for 12, 24 and 72h following injections compared to control untreated hpg males of the same age. Experiment Overall Design: Adult 10 week old hpg males were injected sc with 8 I.U. of rFSH (Gonal F, Serono Pharmaceuticals) in 0.2ml of PBS (Sigma,UK) every 12 h for 12, 24 and 72 h. Mice were killed one hour after the last injection by cervical dislocation, testes dissected out, weighed and snap frozen in liquid nitrogen. Tissue was stored at -70oC until use. RNA was extracted using Qiagen RNeasy Lipid Tissue Mini kit (Qiagen, Valencia, CA) according to the manufacturerâs instructions and quantified on a NanoDrop ND-1000 (NanoDrop Wilmington, DE). RNA quality was checked using the Agilent bioanalyzer 2100 (Agilent, Santa Clara, CA). Testicular gene expression was examined in four individual mice at 12 and 72 h and 3 mice at 24h using high-density oligonucleotide mouse MOE430A arrays (Affymetrix, Santa Clara, CA), comparison was made with a group of 7 untreated hpg males of the same age.
2009-08-22 | E-GEOD-8924 | biostudies-arrayexpress