Daily Endocrinology Research Analysis

Transcription factors play a key role in regulating gene expression. We conduct an integrated analysis of chromatin accessibility, DNA methylation, mRNA expression, protein abundance and phosphorylation across eight tissues in fifty rats of equally represented sexes following endurance exercise training to identify coordinated epigenomic and transcriptional changes and determine key transcription factors involved. We uncover tissue-specific endurance exercise training associated changes and transcription factor motif enrichment across differentially expressed genes, accessible regions, and methylated regions. We discover distinct routes of training-induced regulation through either epigenomic alterations providing better access for transcription factors to affect target genes, or via changes in transcription factor expression or activity enabling target gene responses. We identify transcription factor motifs enriched among correlated epigenomic and transcriptomic alterations, differentially expressed genes correlated with exercise-related phenotypic and cell type composition changes, and training-induced activity changes of transcription factors whose target genes are enriched for differentially expressed genes. This analysis elucidates the unique gene regulatory mechanisms mediating diverse transcriptional responses to training across tissues.

For women with diminished ovarian reserve or of advanced age, controlled ovarian stimulation presents a significant challenge during in vitro fertilization cycles. This multi-center, open-label, randomized controlled trial enrolled 318 women with diminished ovarian reserve (defined as an antral follicle count < 5 or anti-Müllerian hormone level of 0.1-1.1 ng/mL) or advanced age (40-45 years) between 2020 and 2023. Participants were assigned to either a modified letrozole protocol (mLP, n = 159) or a gonadotropin-releasing hormone antagonist protocol (n = 159). Primary outcomes, cumulative clinical pregnancy rate and cumulative live birth rate, were analyzed using both the full analysis set and the per-protocol set. Secondary outcomes, including live birth rate, clinical pregnancy rate, and pregnancy loss rate, were analyzed using the per-protocol set. Results from the full analysis set showed comparable cumulative clinical pregnancy rates (32.1% vs 34.0%; RR 0.94, 95% CI: 0.69-1.29) and cumulative live birth rates (24.5% vs 22.6%; RR 1.08, 95% CI: 0.73-1.61) between the two groups. The per-protocol analysis also demonstrated comparable cumulative clinical pregnancy rates (33.3% vs 36.0%; RR 0.93, 95% CI: 0.68-1.27). Notably, the mLP was associated with a significantly higher clinical pregnancy rate among patients with diminished ovarian reserve who underwent dual cleavage-stage fresh embryo transfers (65.8% vs 36.4%; RR 1.81, 95% CI: 1.15-2.85). Although primary outcomes were similar between protocols, the mLP improved clinical pregnancy rates in fresh embryo transfers for women with diminished ovarian reserve, suggesting its potential to enhance in vitro fertilization efficacy in this population. Fresh transfers demonstrated non-significant difference of mLP for live birth rate (34.0% vs 22.2%; RR 1.53, 95% CI: 0.96-2.43), non-significant reduced biochemical pregnancy loss rate (22.0% vs 34.3%; RR 0.59, 95% CI: 0.29-1.21) and miscarriage rate (20.0% vs 26.7%; RR 0.75, 95% CI: 0.32-1.77). Trial registration: ChiCTR2000029272.

PURPOSE: Type 2 diabetes mellitus (T2D) is associated with an increased burden of neuropsychiatric disorders, including cognitive decline, affective disorders, and substance use disorders. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), developed for glycemic control and weight reduction, have been hypothesized to confer neuroprotective and psychotropic benefits via central and peripheral mechanisms. However, evidence across individual studies remains inconsistent. METHODS: We conducted a systematic review and meta-analysis (PROSPERO CRD420251025534) of randomized controlled trials (RCTs) and observational studies assessing the effect of GLP-1 RAs on neuropsychiatric outcomes. Searches were performed in MEDLINE, SCOPUS, CENTRAL, and Web of Science up to 30 FINDINGS: From 10,037 records, 82 studies were included. GLP-1 RAs were associated with a reduced risk of idiopathic Parkinson's disease (PD) (pooled HR 0.70, 95% CI: 0.53-0.92, I IMPLICATIONS: Current evidence, largely of low to very low certainty, suggests potential selective neuropsychiatric associations of GLP-1 RAs, particularly in Parkinson's disease risk reduction and binge eating disorder. Benefits for dementia risk reduction were observed primarily in comparisons with non-exposed or DPP4i, whereas no advantage was seen versus other active comparators, such as SGLT2 inhibitors. Our findings should be interpreted as hypothesis-generating due to significant heterogeneity and wide confidence intervals, indicating imprecision. Longer-term studies with neuropsychiatric outcomes as the primary endpoint are required.