Project description:Background: The exact nature of the interrelationship between pubertal brain development and hormones involvement has always attracted wide interest. Brain structural changes that occur during the pubertal developmental process mainly appear in the regions most closely linked with emotion, motivation and cognitive functions. Using a sheep model, we have previously shown that peri-pubertal pharmacological blockade of gonadotropin-releasing hormone (GnRH) receptors results in increased sex-differences in cognitive executive function and emotional control, as well as in a sex- and side-specific gene expression pattern of hippocampal genes associated with synaptic plasticity and endocrine signaling. In this study, we explore the effects of this treatment regime on the amygdalar gene expression profile. Methods: The study was conducted with 30 same-sex twin lambs (14 female and 16 male), half of which were treated with the GnRH agonist (GnRHa) goserelin acetate every 4th week, beginning before puberty, until 50 weeks of age. The gene expression profiles of left and right amygdala samples from all 30 animals were measured by using ovine 8 X 15 K Agilent microarrays. Furthermore, differential expression of a selected number of genes was confirmed by qRT-PCR (Quantitative real time PCR). Networking analyses and Gene Ontology (GO) Term analyses were performed with the Ingenuity Pathway Analysis (IPA), version 7.5 DAVID (Database for Annotation, Visualization and integrated Discovery) software packages respectively. Results: GnRHa treatment was associated with significant sex- and hemisphere-specific differential expression of genes. Interestingly, genome-wide transcription showed a set of 438 (p value <0.05) genes in female treated left and 46 (p value <0.0.5) genes in females treated right amygdala were differentially expressed but not in any treatment group of male animals. Conclusion: Our results indicate that GnRH directly and/or indirectly is involved in the regulation of sex- and side-specific differential expression of genes in amygdala. Hence, this finding should be considered when long-term peri-pubertal GnRHa treatment is used in children.
Project description:We evaluated the efficacy of combining pembrolizumab (anti-PD1 antibody), exemestane (nonsteroidal aromatase inhibitor), and leuprolide (gonadotropin-releasing hormone agonist) for 15 patients with ER+/HER2− premenopausal MBC who had failed one to two lines of hormone therapy without chemotherapy.
Project description:We evaluated the efficacy of combining pembrolizumab (anti-PD1 antibody), exemestane (nonsteroidal aromatase inhibitor), and leuprolide (gonadotropin-releasing hormone agonist) for 15 patients with ER+/HER2− premenopausal MBC who had failed one to two lines of hormone therapy without chemotherapy.
2024-10-28 | GSE261380 | GEO
Project description:Transcriptome sequencing of superovulation with the gonadotropin-releasing hormone agonist (GnRHa) trigger in mice
Project description:We used microarrays to detail the global program of gene expression underlying gonadotropin-releasing hormone (GnRH) generation and delamination from the olfactory placode.
Project description:GT1-7 cells were treated with 100 μg/mL HTR1A antagonist WAY-100635 maleate for 6 h and harvested for RNA-seq. This study aimed to investigate the expression of gonadotropin-releasing hormone and the differential expressed genes affected by HTR1A inhibition.
Project description:Hypothalamic gonadotropin-releasing hormone (GnRH) neurons are central regulators of fertility and integrate endogenous hormonal status with environmental cues to ensure reproductive success. Here, we found that extra-hypothalamic GnRH neurons in the olfactory bulb of adult mice and humans (GnRHOB) can mediate social recognition. We show that GnRHOB neurons extend neurites into the vomeronasal organ and olfactory epithelium and project to the hypothalamic median eminence. We demonstrate that male GnRHOB neurons express vomeronasal and olfactory receptors, are activated by female odors in vivo, and mediate gonadotropin release in response to female urine. We find that male preference for female odors is enhanced upon chemogenetic activation of GnRHOB neurons and is impaired after genetic inhibition or ablation of these cells and relies on GnRH signaling in the posterodorsal medial amygdala. Taken together, these results establish GnRHOB neurons as a central regulatory hub regulating fertility, sex recognition, and mating in males.
Project description:GT1-7 cells were treated with 100 μg/mL HTR1A antagonist WAY-100635 maleate for 6 h and harvested for investigation on the genome-wide enrichments of CBX4 and H2AK119ub by ChIP-seq. This study aimed to investigate the regulatory mechanism on expression of gonadotropin-releasing hormone affected by HTR1A inhibition.
Project description:The process of ovulation includes oocyte meiotic maturation, follicle rupture and transformation of the follicle into a corpus luteum. These events are initiated by the midcycle surge of gonadotropins and require the coordinated regulation of thousands of genes. The aim of the study was to monitor the changes in granulosa cell gene expression across five different time points during the first 36 hours of ovulation until follicle rupture, in order to increase our understanding of the events of human ovulation. We conducted a prospective cohort study including women undergoing ovarian stimulation for fertility treatment. Women were treated in a standard antagonist protocol with individually dosed human menopausal gonadotropin (hMG) or recombinant follicle stimulating hormone (rFSH). Ovulation was induced with either recombinant hCG (rhCG) or gonadotropin releasing hormone agonist (GNRHa). The granulosa cells were collected by transvaginal ultrasound-guided follicle puncture of one follicle at two specific time points during ovulation (repeated measurements), and the study covered a total of five time points: before ovulation induction (OI), 12, 17, 32 and 36 hours after OI.
Project description:<p>Introduction: Gonadotropin-releasing hormone (GnRH) is widely used in the timed artificial insemination program of sheep industry, but there is still controversy about the effect of GnRH on pregnancy rate in the process of artificial insemination. Our research shows that the use of GnRH reduces the pregnancy rate. This study aims to analyze the metabolite changes caused by GnRH in Huyang ewes before the implantation period through metabolomics technology, and reveal the mechanism behind the decreased pregnancy rate. </p><p>Methods: All ewes had a polyurethane sponge containing 45 mg of flurogestone acetate placed in their vagina for 12 days, and were intramuscularly treated with 330 units of equine chorionic gonadotropin (eCG) immediately after sponge removal. The experimental group (n = 69) received an intramuscular treatment of 17 μg GnRH agonist triptorelin (Day 0) 48 h after sponge removal, while the control group (n = 41) was treated with 1 mL of sterile saline. All ewes underwent a single vaginal insemination 58 h after the withdrawal of progesterone sponges. The difference in pregnancy rates between the two groups was then measured. Metabolomic analysis was performed on plasma samples collected on Day 7. </p><p>Results: Compared with the control group, GnRH treatment significantly reduced the pregnancy rate in the experimental group (72.2% vs 82.9%, P < 0.05). Metabolomic analysis revealed that GnRH treatment influenced metabolites involved in collagen synthesis and metabolites linked to prostaglandin synthesis in the endometrial tissue, which includes a marked decrease in hydroxyproline metabolite content and a substantial increase in corticosterone and prostaglandin D2 metabolite levels. </p><p>Conclusion: In summary, GnRH agonist Triptorelin injected 48 h after the withdrawal of progesterone sponges can reduce the pregnancy rate of Huyang ewe after artificial insemination and affect the metabolite levels related to endometrial collagen synthesis and prostaglandin synthesis, which are not conducive to embryo implantation.</p>