Abstract: Background/Objectives: Obesity is a growing global health concern with significant implications for female reproductive health, notably contributing to menstrual irregu-larities, anovulation, and infertility. This review explores the relationship between fe-male obesity and reproductive dysfunction, with a particular focus on the impact of bariatric surgery on fertility outcomes. Methods: Drawing from 116 original research studies, the analysis examines the two bariatric surgical techniques, sleeve gastrecto-my (SG) and Roux-en-Y gastric bypass (RYGB), and their effects on weight loss, hor-monal profiles, ovulatory function, and conception rates. Conclusions: Results con-sistently demonstrate improvements in menstrual regularity, resolution of polycystic ovary syndrome (PCOS) symptoms, including improved insulin sensitivity and re-duced hyperandrogenism, increased spontaneous ovulation and enhanced fertility following significant post-surgical weight reduction. Additionally, timing of pregnan-cy after surgery, type of surgical intervention, and degree of weight loss are identified as critical determinants of reproductive success. The review also addresses gaps in long-term data and emphasizes the need for individualized preconception counseling in women with obesity pursuing fertility.

Abstract: Dyslipidemia is a prevalent metabolic disorder and a major cardiovascular risk factor, often influenced by sedentary lifestyles and family history. This study analyzed the association between sedentary behavior, adiposity indicators, and family history with dyslipidemia in young adults from Trujillo in 2025. A cross-sectional correlational design was applied to 137 participants (41 men and 96 women). Sedentary behavior was measured using the IPAQ questionnaire, while family history of dyslipidemia or cardiovascular disease was recorded. Anthropometric indicators included waist circumference (WC), body mass index (BMI), relative fat mass (RFM), body roundness index (BRI), and conicity index (CI). Lipid profiles were assessed with Mission monitoring equipment. HDL-c was low (38.90 ± 16.45 mg/dL in men; 47.42±15.82 mg/dL in women), while LDL-c was slightly elevated (103.39 ± 36.36 mg/dL and 102.74±33.60 mg/dL). Average cholesterol and triglyceride concentrations were normal in both genders. WC, RFM, and BRI correlated with LDL-c, with RFM showing the strongest association (OR = 4.108; 95% CI: 1.266–13.332). Triglycerides were linked to BMI, WC, BRI, and sedentary lifestyle, with WC being most significant (OR = 6.125; 95% CI: 2.007–18.690). In conclusion, RFM and WC emerged as the most robust predictors of dyslipidemia, underscoring their utility for early detection of elevated LDL-c and hypertriglyceridemia in young populations.

Abstract:

The optimal dietary balance between n‑6 and n‑3 polyunsaturated fatty acids (PUFAs), the safe upper intake of n‑6 PUFAs—particularly linoleic acid—and the physiological consequences of their metabolic competition remain unresolved in the context of the Western diet. Since the 1980s, Bill Lands and colleagues have argued that high n‑6 PUFA intake can shift the balance of n‑3–derived pathways and eicosanoid signaling, potentially influencing processes relevant to non‑communicable diseases. Despite its potential public‑health implications, this hypothesis has received limited systematic attention. In this narrative review, we synthesize key aspects of Lands’ work, evaluate supportive and contradictory evidence, and highlight mechanistic insights into lipid competition and inflammatory regulation. We conclude that these unresolved but testable hypotheses warrant renewed investigation, as their corroboration could reshape dietary guidelines and strategies for chronic disease prevention.

Abstract:

Background: Diabetes among adults is becoming a major public health crisis in the United States. Numerous authors have documented the rising prevalence of diabetes, with notable variations found within the United States at the census level, state, and county levels. Yet, there is a need to understand whether diabetes prevalence varies between urban centers within a particular state. Methods: This ecological study provides a longitudinal investigation of the prevalence of adult diabetes across five major metropolitan urban areas in Texas (Austin, Dallas, Fort Worth, Houston, and San Antonio) from 2011 to 2023. By utilizing data from the Behavioral Risk Factor Surveillance System (BRFSS) and statistical testing, we evaluate both the temporal trajectory and city-level geographic disparities of diabetes prevalence. Findings: Upon aggregating all five urban centers, the findings demonstrate a significant statewide increase (β=0.12, P=0.026) in diabetes prevalence over the thirteen-year study period. Furthermore, profound regional variations were observed, with San Antonio having a significantly (P<0.05) higher prevalence than Austin, Dallas, and Fort Worth, with the San Antonio area exhibiting the highest mean prevalence at 12.1% and the Austin area maintaining the lowest at 9%. Interpretation: This research emphasizes the necessity for synchronized public health policies that account for localized contexts while addressing the broader metabolic crisis facing the Texas urban corridor.

Abstract: Background: Benign prostatic hyperplasia (BPH) is a significant health issue among ageing men, with ongoing research focused on elucidating its underlying mechanisms and improving experimental models. Testosterone Propionate (TP) is the first line of choice for the induction of BPH in experimental rodent models. However, TP's controlled status as a Schedule III drug in the United States and a Class C drug in the UK presents challenges in obtaining TP for experimental use, giving preference to the sulpiride model since it is easily obtained as an alternative for the induction and study of BPH. Method: A comprehensive literature search was conducted across multiple electronic databases, including PubMed/MEDLINE, Embase, and Web of Science. The primary PubMed search strategy included combinations of Medical Subject Headings (MeSH) and free-text terms: (“Benign prostatic hyperplasia induction” OR ‘’ and rodent models’’) AND (“Testosterone Propionate model” ) AND (“sulpiride model”). Studies were included if they induced BPH (using testosterone or sulpiride models). Titles and abstracts were screened for relevance; eligible articles underwent full-text review, with data extracted thematically. No formal risk-of-bias scoring was used due to the narrative approach; instead, studies were appraised by design, rigor, plausibility, and evidence. This study reviewed published and publicly available data, so no ethical approval was required. Results: Although both TP and sulpiride induce BPH via various mechanisms, this review provides a comparative analysis of these two commonly utilised models for studying BPH. In the TP approach, castrated rodents receive daily subcutaneous injections for 4 weeks, resulting in dihydrotestosterone (DHT)-mediated epithelial hyperplasia predominantly affecting the ventral prostate lobes. Conversely, the sulpiride model is non-invasive, employs intact animals treated with sulpiride, and induces hyperprolactinemia-mediated BPH via interactions with androgen and oestrogen receptor pathways that stimulate prostatic stromal and epithelial proliferation, particularly in the lateral and dorsal lobes, representing an alternative method. We also highlight the strengths and limitations of TP and sulpiride in replicating clinical symptoms and examine the toxicological effects of sulpiride on the kidney, testis, liver, and brain. Conclusions: we recommend the sulpiride model for the induction and studying of BPH, as it is readily accessible and closely mimics the pathogenesis of BPH in humans, unlike the TP model, which requires castration.

Abstract: This study explored how a high-fiber diet and n-3 fatty acids, alone and together, affect inflammation, oxidative stress, and blood sugar control in mice with type 2 diabetes. Forty diabetic mice were divided into four groups: diabetic control, high-fiber diet (25 g/day), n-3 PUFA (3 g/day), and a combined high-fiber + n-3 PUFA diet. The intervention lasted 16 weeks. The combined group showed the best outcomes, with CRP reduced by 48%, MDA lowered by 42%, SOD activity raised by 58%, and HbA1c decreased by 1.7 ± 0.2%. Gene analysis showed weaker NF-κB and MAPK signaling in the combined group than in single-treatment groups. These findings show that fiber and n-3 fatty acids work together through different but related actions: fiber supports gut health and reduces inflammation, while n-3 fatty acids improve antioxidant activity and help protect cells. This combination may offer a simple dietary approach to support blood sugar and metabolic balance in diabetes, though more long-term human studies are still needed.

Abstract: Pre-diabetes is a metabolic disorder characterised by higher than normal blood glucose levels, resulting in hyperglycemia. As a precursor to diabetes, pre-diabetes remains one of the most detrimental disorders for the larger global health. Improvement in understanding of the gut microbiome has led to the discovery of correlations between species present in the human gut microbiota and the onset of metabolic syndrome. Gut dysbiosis serves as a potent biomarker for the detection of pre-diabetes, and its progression into Type 2 Diabetes Mellitus (T2DM). Key biological processes, including metabolism, inflammation, insulin receptivity, and gut permeability, are impacted by the gut microbiota’s diversity of bacterial taxa and presence of short chain fatty acids (SCFAs), inflammatory markers, cytokines, metabolites, proteins, and lipopolysaccharides (LPS). These markers offer insight on the gut microbiome’s composition and support effective methods of intervention, including for the prevention of transition to T2DM. Obtaining and analyzing host microbiome data and integrating multi-omics approaches requires enhanced computational techniques, including advancements in machine learning. This offers personalised treatment for patients, including fecal transplants, diet, synbiotics, and anti-diabetic drugs. The gut microbiome’s potent influence on pre-diabetes serves as a future direction to improve patient care for glycemic disorders through enhanced therapeutic interventions.

Abstract: Bisphenol A (BPA), a common endocrine disruptor, poses a public health risk due to its potential effects on thyroid function. However, its role in thyroid cancer development remains unclear. This study investigated BPA's genotype-dependent effects on cellular processes in human thyroid cell lines. We exposed a non-tumorigenic thyroid cell line (Nthy-ori 3-1) and two papillary thyroid carcinoma cell lines, BCPAP (BRAF V600E) and TPC-1 (RET/PTC rearrangement), to BPA concentrations (0.1–1.0 µg/mL). Subse-quently, cellular viability, proliferation, and migration were assessed. BPA induced distinct genotype-dependent responses. At higher concentrations (0.8-1.0 µg/mL), non-tumorigenic cells exhibited significant dose-dependent cytotoxicity but paradoxi-cally showed enhanced migration. In the cancerous cell lines, TPC-1 cells did not ex-hibit inhibition of proliferation or changes in migration, while BCPAP cells were rela-tively resistant to cytotoxicity but showed reduced proliferation and significantly im-paired migration. Our findings demonstrate that BPA exerts dual and opposing effects on thyroid cells, depending on the genetic background. These genotype-specific sus-ceptibilities, cytotoxic and pro-migratory effects in normal cells, and in RET/PTC-positive cells, and antimigratory effects in BRAF-mutant cells underscore the complex role of BPA in thyroid pathophysiology. These results demonstrate that ge-netic background is a critical determinant of cellular susceptibility, suggesting that BPA exposure may differentially influence thyroid cancer initiation and progression.

Abstract: Zinc homeostasis is fundamental to metabolic health, orchestrated by the coordinated actions of two major zinc transporter families: ZIP (Zrt- and Irt-like Proteins) and ZnT (Zinc Transporters). ZIP-transporters Facilitates zinc influx into the cytosol from the extracellular space or from the lumen of intracellular organelles, whereas ZnT-transporters control zinc efflux from the cytosol to the extracellular space or facilitate its sequestration into intracellular vesicles and organelles, concurrently harboring the meticulous intracellular zinc homeostasis. This equilibrium is essential for all critical functions like cellular response, metabolic control, or immune pathway alteration. Disruption of this homeostasis is a driver of different pathological alterations like metabolic inflammation, a chronic low-grade inflammatory state underlying obesity, type 2 diabetes, and nonalcoholic fatty liver disease. Recent studies revealed that ZIP and ZnT transporters dynamically regulate metabolic and inflammatory cues, with their tissue-specific expression varying by tissue and acclimating to different physiological and pathological conditions. Recent advanced research in molecular and genetic understanding has helped to deepen our knowledge on the interplay of activity between ZIP and ZnT transporters and their crosstalk in metabolic tissues, underscoring the potential therapeutic prospect for restoring zinc balance and ameliorating metabolic inflammation. This review provides a comprehensive overview that covers the function, regulation, and the interactive crosstalk of ZIP and ZnT zinc transporters in metabolic tissues, and its pathological condition.

Abstract: Obesity treatments increasingly target multiple pathways beyond appetite suppression. We evaluated KBN2202, a salicylate-derived small molecule, in a high-fat diet (60% kcal) mouse model using female and male C57BL/6J mice treated for 8 weeks with oral KBN2202 (20 mg/kg/day) or matched-volume vehicle (1% DMSO/PBS). Body weight and food intake were tracked weekly; serum hormones/cytokines, adipose tissue histology, and open-field behavior were assessed at study end. KBN2202 significantly reduced peri-ovarian gonadal white adipose tissue (gWAT) mass and adipocyte size in females without altering overall body weight. Circulating glucagon-like peptide-1 (GLP-1) increased, uncoupling protein 1 (UCP1) in gWAT showed a non-significant upward trend, and serum TNF-α was selectively decreased, while MCP-1 and IL-1β were unchanged. Despite higher apparent food intake, locomotor activity was unaltered and anxiety-like behavior was reduced. Male mice did not show comparable adipose effects. These findings indicate depot-specific, peripheral modulation of adipose remodeling, hormonal balance, and inflammatory tone by KBN2202, supporting its further investigation as an adipose-targeted metabolic modulator complementary to incretin-based therapies.

Abstract: The objective is to identify the risk factors associated with the development of necrotizing enter-ocolitis in newborns less than 34 weeks old in the INMP ICU during the period 2020-2022. The approach is basic, quantitative, non-experimental, and longitudinal, taking into account a total population of 20,371 newborns treated, but 7.95% of cases (1,620 patients) received an exclusive diagnosis of necrotizing enterocolitis (NEC). Information processing was carried out using the multiple linear regression model with NEC as the dependent variable. The results showed that in the INMP ICU, 7.95% of newborns treated were diagnosed exclusively with necrotizing entero-colitis (NEC). A multiple linear regression model was implemented using the stepwise technique, with NEC as the dependent variable and various independent variables, including maternal, ne-onatal, and other factors related to medical care. Several risk factors associated with the devel-opment of necrotizing enterocolitis in premature newborns under 34 weeks of age in the INMP ICU were identified. These include, among others, chorioamnionitis, neonatal sepsis, and age of occurrence. The presence of chorioamnionitis was shown to be a significant risk factor, with a 0.754-unit increase in the odds of NEC for each unit increase. Neonatal sepsis was also significantly associated with a 1.114-unit increase in the odds of NEC for each unit increase. Therefore, these findings underscore the importance of identifying and adequately managing the risk factors as-sociated with necrotizing enterocolitis in neonatal care in the INMP ICU.

Abstract: The detailed characterization of antigen-specific serum antibodies is hindered by the lack of efficient, gentle isolation methods. Standard column affinity chromatography, despite being a powerful purification tool, presents practical challenges for this application, including high antigen consumption, and elution conditions that risk inducing antibody polyreactivity. Conventional acidic elution often compromises antibody integrity. This study introduces a novel microscale method for isolating specific immunoglobulins using anionic detergents as mild eluents. We employed antigen-functionalized hydrogel microarrays and magnetic beads as micro-immunosorbents. Among the detergents tested, sodium lauroyl glutamate (SLG) was optimal, achieving up to 78.3% recovery of functional antibodies. The optimized protocol including recovering G25-Sephadex gel filtration step effectively isolated specific antibodies from complex serum, with functional bioactivity retained between 58.5% and 85.3%. Multiplex immunoassays confirmed the high specificity of the isolated antibodies and the absence of detergent-induced polyreactivity. The method was successfully adapted for both specific antibody (virus, dietary and autoimmune) and total IgG isolation, demonstrating versatility across platforms. This work establishes a robust, efficient, and gentle workflow for obtaining high-purity, bioactive antibodies, enabling their subsequent in-depth analysis for research applications.

Abstract:

Background: Local specific biomarkers for MASLD risk stratification are urgently needed in Argentina. Aim: To characterized the interaction of gut microbiome signatures, genetic and clinical risk factors for MASLD in diabetics from different regions of Argentina. Material Methods: We recruited 214 diabetics from different regions. Anthropometric, clinical, and lifestyle data were obtained from all participants, who also underwent abdominal ultrasound for MASLD diagnosis and oral swabbing. PNPLA3 gene was amplified by PCR from the swabs, and rs738409 genotype was determined by bidirectional sequencing. To profile the MASLD-associated microbiome, stool was collected from 170 participants. V4 16S rRNA gene sequencing was performed and reads were analysed using QIIME2 2024.10.1. R Studio 2022.12.0 was used for statistical analyses. Results: MASLD prevalence was 77.9%, with similar rates in all regions. FIB-4 scores <1.3 and >2.67 were detected in 55.3% and 7.4% of patients, respectively. Half of diabetics had PNPLA3-GG genotype, with the highest rates in Northwestern Argentina (64.9%; p=0.02 vs Buenos Aires). PNPLA3-GG genotype was an independent risk factor for FIB-4 score (p=0.0008), and a protective factor against HbA1c (p=0.004), fasting plasma glucose (p=0.008), and cholesterol levels (p=0.02). Marked regional differences were observed in microbiota diversity and composition in Argentina. After adjusting for geographical region, Negativibacillus genus was exclusively detected in diabetics with MASLD and GG carriers. Catenibacterium genus was related to FIB-4>2.67. Short-chain fatty acids-producing bacteria were linked to absence of MASLD. Conclusions: These specific signatures could be potentially useful as MASLD biomarkers for risk stratification in diabetics from Argentina.

Abstract: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disorder in both children and adults. Pediatric MASLD, however, is not simply an early form of adult disease, as it exhibits distinct developmental, histological, and metabolic features. These characteristics reflect the complex, multi-hit, developmental continuum that begins in utero. Maternal obesity, gestational diabetes, and poor diet quality during pregnancy are linked to hepatic steatosis in offspring, implicating intra-uterine exposure to dyslipidemia, hyperglycemia, and excess free fatty acid flux as ini-tiators of fetal hepatic lipid deposition. After birth, feeding behaviors such as a prolonged duration of breastfeeding appears protective, while formula feeding, especially high added-sugar formulations, may accelerate rapid weight gain and predispose to later steatosis. Early childhood diets high in added sugars, saturated fats, and ultra-processed foods may further promote hepatic lipogenesis and inflammation and reveal underlying genetic susceptibility to metabolic dysfunction. This narrative review summarizes recent human and translational studies examining the relationship between prenatal, postnatal, and early childhood nutrition and offspring hepatic lipid accumulation, emphasizing early-life windows for intervention to reduce the burden of pediatric MASLD.

Abstract: This review focuses on the molecular pathogenesis of Type 1 diabetes (T1D), specifically on the key autoantigens targeted by the autoimmune response and the clinical implications of their epitope specificity. T1D is characterized by the destruction of insulin-producing pancreatic β-cells. The autoimmune attack is directed against a defined set of autoantigens, primarily insulin, glutamic acid decarboxylase 65, tyrosine phosphatase-like protein, zinc transporter 8, as well as several minor autoantigens. A critical advancement in understanding the disease has been the analysis of epitope specificity, revealing that immunodominant epitopes are conformational and often localized to C-terminal protein regions, exposed during β-cell degradation. The introduction of sensitive multiplex assays for the simultaneous detection of T1D-associated autoantibodies represents a major diagnostic breakthrough. These platforms enable early diagnosis, risk stratification, and the identification of a "therapeutic window" for intervention. At this preclinical stage, antigen-specific immunotherapies aimed at restoring immune tolerance show significant promise. Ultimately, the combination of personalized diagnostic profiles, epitope mapping, and targeted therapies forms the basis for a new T1D management paradigm focused on halting the autoimmune process itself and preserving functional β-cell mass.

Abstract: Insulin resistance (IR) describes impaired hormone signaling that triggers compensatory homeostatic responses resulting in hyperinsulinemia, increased accumulation of fatty substrates, lipotoxicity, oxidative stress, inflammation, cell death and fibrosis in target tissues. These processes ultimately lead to organ dysfunction and predispose certain individuals to various types of cancer. In this context, we will review the molecular pathogenesis and clinical significance of IR, its role in ‘metaflammation’, and the damage caused by IR in the pancreas, cardiovascular system, liver, and kidneys. Additionally, we will discuss principles of drug treatment for IR and outline a research agenda in this field.

Abstract: Previous studies suggest that the cortisol awakening response (CAR) shows a biphasic pattern—either an increase or a blunting—in reaction to exercise involving overload. These changes are considered to reflect physiological adaptation to exercise. However, the effects of continuous exercise on CAR under controlled experimental conditions have not been sufficiently explored. This study examined changes in CAR in response to short-term, continuous high-intensity cycling exercise over a 10-day period. Two healthy male participants underwent 12 consecutive days of experimental sessions: 2 baseline rest sessions followed by 10 days of cycling exercise sessions (20 min/day at 80% of maximal oxygen uptake [VO₂max]). CAR was measured daily throughout this period. Acute physiological responses and aerobic capacity were also assessed. Results showed that CAR increased during Days 1–4 of the exercise period and returned to baseline levels from Day 5 onward. Similar trends were observed in physiological responses. Additionally, participants demonstrated improvements in VO2max and/or maximum workload following the experimental sessions. These findings suggest that CAR could be a useful non-invasive biomarker for monitoring short-term physiological adaptation to high-intensity exercise.

Abstract: Women often notice monthly shifts in energy, mood, and appetite, prompting questions about whether lunar phases also play a role. This paper synthesizes current literature to explore how menstrual cycle–driven hormonal fluctuations—particularly shifts in estrogen and progesterone—affect macronutrient metabolism, cravings, and exercise performance, with a focus on increased appetite and subtle performance variations in the luteal phase. It further examines evidence for potential lunar effects, including studies suggesting modest correlations between moon phases, menstrual onset timing, and sleep disruptions, even though modern lifestyles often obscure such rhythms. For those who do not menstruate—such as postmenopausal women—adopting a monthly or “lunar” framework may still help address cyclical changes in mood or energy. Practical recommendations highlight “cycle syncing” via chrononutrition (aligned meal timing and composition) and targeted exercise based on hormonal states, while also acknowledging debates around any direct lunar impact. Ultimately, emerging findings emphasize the importance of personalized tracking, and future research with rigorous hormonal verification and sleep monitoring is needed to clarify the extent to which lunar considerations enhance health outcomes.

Abstract: Background/Objectives: Type 2 diabetes and obesity present escalating global health and economic challenges, highlighting the need for therapies that can effectively manage glycemic levels and reduce excess adiposity. Semaglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist available in subcutaneous or oral formulation, has quickly evolved from a theoretical concept to a crucial component of modern metabolic care. This review explores the comprehensive development journey of semaglutide, drawing on evidence from medicinal chemistry, animal studies, initial human trials, the pivotal SUSTAIN and STEP programs, and real-world post-marketing surveillance. Methods: We conducted a detailed analysis of preclinical data sets, Phase I–III clinical trials, regulatory documents, and pharmaco-epidemiological studies published between 2008 and 2025. Results: Through strategic molecular modifications, such as specific amino-acid substitutions and the addition of a C18 fatty-diacid side chain to enhance albumin binding, the half-life of the peptide was extended to approximately 160 hours, allowing for weekly dosing. Studies in rodents and non-human primates showed that semaglutide effectively lowered blood glucose levels, reduced body weight, and preserved β-cells while maintaining a favorable safety profile. Phase I trials confirmed consistent pharmacokinetics and tolerability, while Phase II trials identified 0.5 mg and 1.0 mg once weekly as the most effective doses. The extensive SUSTAIN program validated significant reductions in HbA1c levels and weight loss compared to other treatments, as well as a 26% decrease in the relative risk of major adverse cardiovascular events (SUSTAIN-6). Subsequent STEP trials expanded the use of semaglutide to chronic weight management, revealing that nearly two-thirds of patients experienced a body weight reduction of at least 15%. Regulatory approvals from the FDA, EMA, and other regulatory agencies were obtained between 2017 and 2021, with ongoing research focusing on metabolic dysfunction-associated steatohepatitis, cardiovascular events, and chronic kidney disease. Conclusions: The trajectory of semaglutide exemplifies how intentional peptide design, iterative translational research, and outcome-driven clinical trial design can lead to groundbreaking therapies for complex metabolic disorders.

Abstract: Progesterone (P4) withdrawal is the key trigger for labor onset. Labor is a sterile inflammatory process involving monocyte infiltration, differentiation into M1 or M2 macrophages (Macs) and contributing to the inflammatory milieu in the uterus. Premature leukocyte influx may lead to preterm birth. Inflammatory stimuli induce intracellular progesterone (P4) withdrawal in myometrial cells (MYO) through activation of P4 metabolizing enzyme 20alpha-hydroxysteroid dehydrogenase (20α-HSD). We hypothesized that; (1) the pro-inflammatory M1-Macs induce 20α-HSD in MYO, which causes P4 withdrawal and MYO contractility; and (2) IL-1α produced by M1-Macs mediate the effect of M1-Macs on intracellular P4 withdrawal in MYO. Human myometrial biopsies from women in labor (TL) and not in labor (TNL) revealed higher IL-1α in TL, with M1-Macs in TNL expressing more IL-1α than MYO. In-vitro study shows; (1) higher expression of IL-1α in M1-Macs compared to M2-Macs; (2) treatment of MYO with IL-1α or M1-Macs increased 20α-HSD and contractility; and (3) blockade of IL-1α, AP-1 transcription factors, or co-treatment with non-metabolizable progestin; R5020 inhibits these effects. Our findings highlight the role of tissue-resident M1-Macs in regulating intracellular P4 metabolism and suggest that M1-Macs-derived IL-1α may facilitate P4-withdrawal and uterine contractility associated with labor onset.