Hormone Production Research Articles

Origins and molecular mechanisms underlying renal vascular development.

Kidneys play a crucial role in maintaining homeostasis within the body, and this function is intricately linked to the vascular structures within them. For vascular cells within the kidney to mature and perform their functions effectively, it is imperative that there is a meticulous and well-coordinated spatial alignment between the nephrons and the intricate network of blood vessels within the organ. This spatial arrangement ensures efficient filtration of blood and regulation of the electrolyte balance, blood pressure, and fluid levels. Additionally, the kidneys play a vital role in the regulation of acid-base balance and the production of hormones involved in erythropoiesis and blood pressure regulation. Thus, the close interaction between the vascular system and the kidney's structural organization is essential for maintaining overall physiological balance and health. This article focuses on the vascular development of the kidneys, summarizing the current understanding of the origin and formation of the renal vasculature, and the crucial molecules involved. By elucidating the cellular and molecular mechanisms governing renal vascular development, this article aims to promote advancements in renal regenerative medicine and provide potential avenues for therapeutic interventions to address kidney disease.

Coordinated influence of Funneliformis mosseae and different plant growth-promoting bacteria on growth, root functional traits, and nutrient acquisition by maize.

Rhizospheric interactions among plant roots, arbuscular mycorrhizal fungi, and plant growth-promoting bacteria (PGPB) can enhance plant health by promoting nutrient acquisition and stimulating the plant immune system. This pot experiment, conducted in autoclaved soil, explored the synergistic impacts of the arbuscular mycorrhizal fungus Funneliformis mosseae with four individual bacterial strains, viz.: Cronobacter sp. Rz-7, Serratia sp. 5-D, Pseudomonas sp. ER-20 and Stenotrophomonas sp. RI-4A on maize growth, root functional traits, root exudates, root colonization, and nutrient uptake. The comprehensive biochemical characterization of these bacterial strains includes assessments of mineral nutrient solubilization, plant hormone production, and drought tolerance. The results showed that all single and interactive treatments of the mycorrhizal fungus and bacterial strains improved maize growth, as compared with the control (no fungus or PGPB). Among single treatments, the application of the mycorrhizal fungus was more effective than the bacterial strains in stimulating maize growth. Within the bacterial treatments, Serratia sp. 5-D and Pseudomonas sp. ER-20 were more effective in enhancing maize growth than Cronobacter sp. Rz-7 and Stenotrophomonas sp. RI-4A. All bacterial strains were compatible with Funneliformis mosseae to improve root colonization and maize growth. However, the interaction of mycorrhiza and Serratia sp. 5-D (M + 5-D) was the most prominent for maize growth improvement comparatively to all other treatments. We observed that bacterial strains directly enhanced maize growth while indirectly promoting biomass accumulation by facilitating increased mycorrhizal colonization, indicating that these bacteria acted as mycorrhizal helper bacteria.

Testosterone-promoting effects of Trichosanthes kirilowii-derived peptides on TM3 cells

Bioactive peptides have been shown to have a variety of functions, but very few studies have tapped into their promotional effects and mechanisms on testosterone synthesis. The aim of this study was to investigate the effect of Trichosanthes kirilowii-derived peptide on testosterone synthesis in TM3 cells and its mechanism of action. In this study, we found that the peptide purification fraction TSH1-3 and the peptide VTPVGSPR from Trichosanthes kirilowii seed hydrolysate (TSH) significantly promoted the synthesis of testosterone, dihydrotestosterone, free testosterone, and androstenedione in TM3. Furthermore, TSH1-3 regulates the expression of testosterone synthesis-related genes and proteins StAR, TSPO, CYP11A1, and 3β-HSD in a dose-dependent manner. In addition, given the strong link between mitochondrial biogenesis and testosterone synthesis, we further found that both TSH1-3 and VTPVGSPR promoted mtDNA production and up-regulated the expression of genes important for mitochondrial biogenesis, PGC-1α, TFAM, TFB1M, TFB2M, NRF1 and NRF2. In short, this study demonstrates that TSH can be used as a potential dietary supplement to promote sex hormone production and regulate physical health.

Effectiveness of Prenatal Gentle Yoga to Improve Norephinefrine Levels in Primigravida and Multigravida Pregnant Women at Pkm Makassar City Region

Pregnant women are at risk of experiencing anxiety and stress which causes the release of the hormone norepinephrine which is produced by most neurons in the brain stem and hypothalamus. Yoga has a positive impact on the body by reducing the performance of the hypothalamus, thereby releasing neuropeptides which stimulate the pituitary gland and releasing ACTH which suppresses the production of stress hormones. Prenatal Gentle Yoga is a therapy that supports the healthy balance between body and mind that is needed during the process of pregnancy until delivery. This research was carried out at the Bara Baraya Health Center, Antang Health Center, Kapasa Health Center, and Mamajang Health Center. The research design used in this research is Quasi Experiment with a Nonequivalent Control Group Design approach. Sampling used a purposive sampling technique. The instrument used is ELISA (Enzyme Linked Limmuno Sorbent Assay). The research sample consisted of 24 respondents, 12 people in the intervention group, and 12 people in the control group. Criteria in this research; Primigravida and multigravida pregnant women, pregnant women in the II-III trimester with a gestational age of >=20 to <31 weeks, pregnant women without complications in pregnancy. Based on statistical tests (Mann Whitney Test), norepinephrine levels in the intervention group decreased (p=0.008), there was a significant difference, in the control group the statistical test showed no significance (p=0.347). Thus, prenatal gentle yoga is effective in reducing levels of the hormone norepinephrine.

WITHDRAWN: Comparing English- and Spanish-Reading Patients’ Comprehension of the Drug Facts Label for a New Over-The-Counter Oral Contraceptive

BackgroundHealth literacy is known to impact health outcomes in a multitude of ways and is impacted by language barriers. Lower health literacy is also associated with higher rates of unintended pregnancies. A progestin-only oral hormonal contraception product, norgestrel (Opill-Perrigo), was approved for over-the-counter (OTC) use in the United States in July 2023. Objective(s): The objective was to utilize a knowledge assessment survey to determine participants’ comprehension of norgestrel from its drug facts label and compare the comprehension between primarily English- and Spanish-reading participants. MethodsA 7-item knowledge assessment was developed and distributed to English and Spanish readers at one site within a network of federally qualified health centers. English-reading participants completed the English survey alongside use of an English copy of norgestrel’s drug facts label. Spanish-reading participants completed the Spanish survey and were randomized in a 1:1 fashion to either receive an English or Spanish copy of norgestrel’s drug facts label. ResultsThe English-reading/English label (E/E) group had a higher level of comprehension of norgestrel’s drug facts label compared to the Spanish-reading/English label (S/E) or Spanish-reading/Spanish label (S/S) groups. ConclusionDifferences exist in OTC label comprehension for norgestrel based on primary language able to be read. Advocacy for OTC labels to be readily available in languages other than English is imperative to mitigate unintended pregnancies associated with lower levels of health literacy.

Mechanisms of spinophilin-dependent pancreas dysregulation in obesity.

Spinophilin is an F-actin binding and protein phosphatase 1 (PP1) targeting protein that acts as a scaffold of PP1 to its substrates. Spinophilin knockout (Spino-/-) mice have decreased fat mass, increased lean mass, and improved glucose tolerance, with no difference in feeding behaviors. Although spinophilin is enriched in neurons, its roles in nonneuronal tissues, such as β cells of the pancreatic islets, are unclear. We have corroborated and expanded upon previous studies to determine that Spino-/- mice have decreased weight gain and improved glucose tolerance in two different models of obesity. We have identified multiple putative spinophilin-interacting proteins isolated from intact pancreas and observed increased interactions of spinophilin with exocrine, ribosomal, and cytoskeletal protein classes that normally act to mediate peptide hormone production, processing, and/or release in Leprdb/db and/or high-fat diet-fed (HFF) models of obesity. In addition, we have found that spinophilin interacts with proteins from similar classes in isolated islets, suggesting a role for spinophilin in the pancreatic islet. Consistent with a pancreatic β cell type-specific role for spinophilin, using our recently described conditional spinophilin knockout mice, we found that loss of spinophilin specifically in pancreatic β cells improved glucose tolerance without impacting body weight in chow-fed mice. Our data further support the role of spinophilin in mediating pathophysiological changes in body weight and whole body metabolism associated with obesity. Our data provide the first evidence that pancreatic spinophilin protein interactions are modulated by obesity and that loss of spinophilin specifically in pancreatic β cells impacts whole body glucose tolerance.NEW & NOTEWORTHY To our knowledge, these data are the first to demonstrate that obesity impacts spinophilin protein interactions in the pancreas and identify spinophilin specifically in pancreatic β cells as a modulator of whole body glucose tolerance.

Role of Quaternary Aminoacid Derivatives and Ion Homeostasis in Amelioration of Salinity Stress

Salinity is a detriment to plant production throughout the world. Salinity impacts the quality of irrigation water. Understanding salt stress in plants necessitates complex physiological and metabolic stages. Preserving turgescent cells and regulating the water potential to maintain a proper water balance among the key responsibilities of osmoprotectants, long-term, high salt doses can slow down plant growth and development by interfering with physiological processes like nutrient imbalance, membrane damage, enzyme inhibition and metabolic dysfunctions like photosynthesis, hormone production and ion homeostasis, all of which can result in plant death. Hyperionic and hyperosmotic stress are also caused by prolonged, high salt doses. Osmolytes (such as proline and glycine betaine) accumulate under different salt levels, antioxidant enzyme activities increase and eventually some of the negative effects of NaCl toxicity on plants are mitigated. Plants under salt stress may have higher concentrations of reactive oxygen species (ROS) such as superoxide radicals (O2) and hydrogen peroxide (H2O2). Ion homeostasis is crucial for plants during abiotic stress conditions.

A cytochrome P450 monooxygenase (CYP337B5) plays a key role in regulating juvenile hormone biosynthesis and degrading chlorantraniliprole in Spodoptera frugiperda (Lepidoptera: Noctuidae)

Cytochrome P450 monooxygenase (P450) has been shown to be involved in the detoxification metabolism of exogenous drugs or regulates the endogenous synthesis of juvenile hormone III (JH III). However, it is not yet known whether a particular P450 gene involved in the metabolism also affects the synthesis of juvenile hormones. Fall armyworm (FAW, Spodoptera frugiperda) showed a significant increase in juvenile hormone I (JH I) and juvenile hormone II (JH II) under chlorantraniliprole stress, and 11 chlorantraniliprole resistance-related P450 genes were significantly up-regulated. Among them, CYP337B5 was not only overexpressed in the midgut and head of FAW larvae, but also significantly increased in the female and male adult stages with high JH I and JH II titers. Injecting double-stranded RNA significantly reduced the metabolism rate of chlorantraniliprole in FAW and inhibited the production of juvenile hormones. Additionally, the degradation rates of chlorantraniliprole were significantly increased along with the production of various metabolites when incubated in vitro using recombinant CYP337B5; and JH I and JH II were also increased to some extent by 1.2 and 0.5 times. The results show that CYP337B5 is efficiently involved in the metabolism of chlorantraniliprole and specifically involved in the synthesis of JH I and JH II. We show that some P450s may have dual functions of endogenous hormone synthesis and exogenous substance metabolism in insects, which may be the root cause of the cost of drug resistance in insects.

Hubungan Status Gizi dengan Usia Menarche pada Siswi SMP Kabupaten Ngada

Menarche is an important sign for a woman because it indicates normal hormone production made by the hypothalamus and then passed on to the ovaries and uterus. Late menarche can cause reproductive health problems in women. This study focuses on understanding the relationship between nutritional status and late menarche, which is still a major problem in adolescent reproductive health issues. This study aims to determine the relationship between nutritional status and age of menarche among junior high school students in Ngada Regency in 2023. The type of research used was an analytic survey with a research design using a Case-Control Study approach. The sample in this study was 94 female students, who were divided into 47 female students who experienced late menarche and 47 female students who experienced normal menarche among junior high school students in Ngada Regency. The analysis data used was univariate, bivariate, and odds ratio with the chi-square test. The results showed that those who had a relationship with the incidence of menarche were parents' income (p = 0.023), body mass index (p = 0.002) and food consumption patterns(p = 0.000). In contrast, psychological conditions had no relationship with the incidence of menarche in junior high school students, with a p-value = 0.168. Factors associated with the incidence of menarche are parents' income, nutritional status as measured using BMI and food consumption patterns as measured through the food frequency forum.

Synergistic Methods for Chromium Cleanup Using Plant-Growth-Promoting Bacteria

Chromium (Cr) pollution contributes a significant threat to environmental and human health due to its widespread industrial use and toxic effects. Among the various remediation strategies, the application of plant-growth-promoting bacteria (PGPB) has emerged as a promising approach. The article explores the synergistic potential of PGPB in enhancing plant-based remediation techniques for chromium cleanup. PGPBs enhance plant growth and stress tolerance through mechanisms such as hormone production, nitrogen fixation, and pathogen inhibition. Key strategies discussed include bioaugmentation, biostimulation, phytoextraction, and phytostabilization. These methods leverage the abilities of PGPB to promote plant growth, enhance chromium uptake, and immobilize chromium in the soil, thereby reducing its bioavailability and mobility. Case studies and experimental evidence highlight the effectiveness of PGPB in chromium-contaminated environments, demonstrating improved plant growth and metal accumulation. This review underscores the need for interdisciplinary collaboration, field-scale implementation, and ongoing research to harness the full potential of PGPB-mediated phytoremediation for sustainable chromium cleanup.

Disturbance of Fetal Growth by Azithromycin Through Induction of ER Stress in the Placenta.

Aim: Azithromycin (AZM) is widely used to treat mycoplasma infection in pregnancy. However, there is no adequate evaluation of its side effect on the placenta. In this study, using human placental syncytiotrophoblasts and a mouse model, we investigated whether AZM use in pregnancy might adversely affect placental function and pregnancy outcome. Results: Transcriptomic analysis of AZM-treated human placental syncytiotrophoblasts showed increased expression of endoplasmic reticulum (ER) stress-related genes and decreased expression of genes for hormone production and growth factor processing. Verification studies showed that AZM increased the abundance of ER stress mediators (phosphorylated eIF2α, activating transcription factor 4 [ATF4], and C/EBP Homologous Protein [CHOP]) and decreased the abundance of enzymes involved in progesterone and estradiol synthesis (STS, CYP11A1, and CYP19A1) and insulin-like growth factor binding protein (IGFBP) cleavage (PAPPA and ADAM12) in human placental syncytiotrophoblasts. Inhibition of ER stress blocked AZM-induced decreases in the expression of CYP19A1, CYP11A1, PAPPA, and ADAM12, suggesting that the inhibition of AZM on those genes' expression was secondary to AZM-induced ER stress. Further mechanism study showed that increased ATF4 in ER stress might repressively interact with C/EBPα to suppress the expression of those genes, including CEBPA itself. Mouse studies showed that AZM administration decreased fetal weights along with increased ER stress mediators and decreased levels of insulin-like growth factor, estrogen, and progesterone in the maternal blood, which could be alleviated by inhibition of ER stress. Innovation and Conclusion: These findings first support the fact that AZM, often used during pregnancy, may affect fetal growth by inhibiting crucial enzymes for estrogen and progesterone synthesis and disrupting crucial proteases for IGFBP cleavage via inducing ER stress in placental syncytiotrophoblasts.

Central Precocious Puberty in a 5-year-old Boy with Hypothalamic Hamartoma: A Case Report and Review of the Literature

Background: Central precocious puberty (CPP) occurs due to the precipitous production of gonadotropin-releasing hormone (GnRH) and premature activation of the hypothalamic-gonadal axis. It is the most typical endocrine symptom of hypothalamic hamartoma. Hypothalamic hamartomas (HH) are rare, non-cancerous malformations of the central nervous system (CNS). They can show up as CPP related to the release of luteinizing hormone in addition to developmental delay, visual impairments, hyperactivity, or gelastic seizures in young children. Case Description: In this study, we present the case of a five-year-old Afghan child who displayed quickly evolving secondary sexual traits linked to hypothalamic dysfunction. Endocrine testing supported the central underlying cause of early puberty. The early detection of a small-sized, rounded lesion at the base of the tuber-cinereum on Magnetic Resonance Imaging (MRI) led to the diagnosis of Hypothalamic hamartoma (HH). To delay puberty, the patient was treated conservatively with a long-acting gonadotropin-releasing hormone (GnRH) analogue and his response was monitored. Conclusion: This case report includes a review of the relevant literature as well as possible management strategies for a hypothalamic hamartoma.

The Efficacy of β-Carotene in Cow Reproduction: A Review.

β-carotene supplementation improves the reproductive performance of cattle. However, the research results on this topic have been inconsistent, and no clear conclusion has been reached. In previous reviews of this topic, the functional mechanism of β-carotene in reproduction remained unclear, but subsequent studies have shown that the antioxidant effects of β-carotene protect enzymes involved in ovarian sex steroid hormone production from the effects of oxygen radicals. This role consequently affects normal ovarian follicle dynamics, maintenance of luteal function, and the estrous cycle, and indirectly improves reproductive performance by preventing perinatal diseases and facilitating recovery from these diseases. Several factors must be considered in feeding management to determine whether β-carotene supplementation is effective for improving reproductive performance in cows. The same is true when the animal consumes a large amount of the antioxidant β-carotene due to lactation, aging, or season. Therefore, it is important to consider the balance between the supply and consumption of β-carotene and evaluate whether β-carotene supplementation has an effect on reproductive performance in cows.

A review of mitotane in the management of adrenocortical cancer.

Mitotane (Lysodren, o,p'-DDD [1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2-dichloroethane)] is currently the only United States Food and Drug Administration and European Medicines Agency-approved product for the treatment of adrenocortical carcinoma. Mitotane is challenging to administer; however, its toxicities (specifically adrenal insufficiency) are well known, and the management of adverse consequences has established approaches. While often viewed through the prism of a cytotoxic agent, it can also interfere with hormone production making it a valuable asset in managing functional ACC. A recently completed prospective trial has shed some light on its use in the adjuvant setting, but further clarity is needed. Many think mitotane has a role in the advanced or metastatic setting, although prospective data are lacking and retrospective analyses are often difficult to interpret. When used carefully and thoughtfully, especially in patients with hormonal excess, mitotane is an important component of the treatment armamentarium for ACC.

Review of clinical practice guidelines for hypoparathyroidism

Hypoparathyroidism is an endocrine disease characterized by reduced production of parathyroid hormone by the parathyroid glands or tissue resistance to its action. This is accompanied by disturbances in phosphorus-calcium metabolism.The main cause of hypoparathyroidism is damage or removal of the parathyroid glands during surgery on the neck organs. Autoimmune hypoparathyroidism is the second most common form of the disease, which occurs, as a rule, within the autoimmune polyglandular syndrome type 1.The development of chronic hypoparathyroidism of any etiology requires lifelong appointment of multicomponent therapy, as well as careful monitoring and an individual approach. In the absence of adequate dynamic monitoring, multiple complications develop from vital organs, in particular calcification of the urinary system, soft tissues and the brain; cardiovascular pathology; visual disturbances; muscle and bone diseases leading to decreased quality of life of patients.Thus, timely diagnosis, rationally selected drug therapy and competent patient management will reduce the risks of complications, improve the prognosis, and reduce the frequency of hospitalizations and disability of patients with chronic hypoparathyroidism.The article presents the main recommendations of the new project of clinical guidelines for patients with hypoparathyroidism, approved by the Ministry of Health of the Russian Federation in 2021. They include the algorithms of diagnosis, treatment and dynamic monitoring of hypoparathyroidism, as well as management of postsurgical hypocalcemia and medical care of and the disease during pregnancy.

High levels of mitochondrial dynamics, autophagy, and apoptosis contribute to stable testicular status in hibernating Daurian ground squirrels

Daurian ground squirrels (Spermophilus dauricus) experience various stress states during winter hibernation, but the impact on testicular function remains unclear. This study focused on the effects of changes in testicular autophagy, apoptosis, and mitochondrial homeostasis signaling pathways at various stages on the testes of Daurian ground squirrels. Results indicated that: (1) During winter hibernation, there was a significant increase in seminiferous tubule diameter and seminiferous epithelium thickness compared to summer. Spermatogonia number and testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels were higher during inter-bout arousal, suggesting that the testes remained stable during hibernation. (2) An increased number of mitochondria with intact morphology were observed during hibernation, indicating that mitochondrial homeostasis may contribute to testicular stability. (3) DNA fragmentation was evident in the testes during the hibernation and inter-bout arousal stages, with the highest level of caspase3 enzyme activity detected during inter-bout arousal, together with elevated levels of Bax/Bcl-2 and Lc3 II/Lc3 I, indicating an up-regulation of apoptosis and autophagy signaling pathways during hibernation. (4) The abundance of DRP1, MFF, OPA1, and MFN2 proteins was increased, suggesting an up-regulation of mitochondrial dynamics-related pathways. Overall, testicular autophagy, apoptosis, and mitochondrial homeostasis-related signaling pathways were notably active in the extreme winter environment. The well-maintained mitochondrial morphology may favor the production of reproductive hormones and support stable testicular morphology.

The Improvement Effects of a Nutritional Fortifier on the Reproductive Performance, Sex Steroid Hormone Production, and Health of the Striped Bamboo Shark Chiloscyllium plagiosum.

To explore a method of improving the reproductive performance of the striped bamboo shark, three groups (D0, D1, and D2) of mature individuals were fed squid with (D1 and D2) or without (D0) a nutritional fortifier during the breeding seasons of 2022 and 2023. Compared with the D0 group, the D1 and D2 groups had an increase of 20.90% and 31.34% in total eggs, increases of 32.73% and 41.82% in the proportion of lecithal eggs, and a total 119.07% increase in hatching rate, respectively, in 2022. In 2023, the corresponding increase was 17.12% and 9.91% in total eggs, 19.63% and 12.15% in the proportion of lecithal eggs, 43.37% and 43.94% in fertilization rate, 23.94% and 22.22% in hatchability rate, and 66.70% and 8.70% in the survival rate of fry. Moreover, the levels of serum estradiol, testosterone, progesterone, albumin, and total antioxidant capacity and the levels of ARA, EPA, DHA, n-3 PUFA, and n-6 PUFA in both serum and lecithal eggs significantly increased, while the levels of serum triglyceride and total cholesterol were the opposite (p < 0.05). The results demonstrate that feeding the sharks with a nutritional fortifier can increase spawn production and the quality of eggs, regulate the production of sex steroids, and improve the nutrition of eggs and the health of broodstocks.

Rebalancing the Gut: Glucagon-Like Peptide-1 Agonists as a Strategy for Obesity and Metabolic Health.

Obesity significantly impacts gut microbial composition, exacerbating metabolic dysfunction and weight gain. Traditional treatment methods often fall short, underscoring the need for innovative approaches. Glucagon-like peptide-1 (GLP-1) agonists have emerged as promising agents in obesity management, demonstrating significant potential in modulating gut microbiota. These agents promote beneficial bacterial populations, such as Bacteroides, Lactobacillus, and Bifidobacterium, while reducing harmful species like Enterobacteriaceae. By influencing gut microbiota composition, GLP-1 agonists enhance gut barrier integrity, reducing permeability and systemic inflammation, which are hallmarks of metabolic dysfunction in obesity. Additionally, GLP-1 agonists improve metabolic functions by increasing the production of short-chain fatty acids like butyrate, propionate, and acetate, which serve as energy sources for colonocytes, modulate immune responses, and enhance the production of gut hormones that regulate appetite and glucose homeostasis. By increasing microbial diversity, GLP-1 agonists create a more resilient gut microbiome capable of resisting pathogenic invasions and maintaining metabolic balance. Thus, by shifting the gut microbiota toward a healthier profile, GLP-1 agonists help disrupt the vicious cycle of obesity-induced gut dysbiosis and inflammation. This review highlights the intricate relationship between obesity, gut microbiota, and GLP-1 agonists, providing valuable insights into their combined role in effective obesity treatment and metabolic health enhancement.

IRAK4 is an immunological checkpoint in neuropsychiatric systemic lupus erythematosus

The search for dementia treatments, including treatments for neuropsychiatric lupus (NPSLE), has not yet uncovered useful therapeutic targets that mitigate underlying inflammation. Currently, NPSLE’s limited treatment options are often accompanied by severe toxicity. Blocking toll-like receptor (TLR) and IL-1 receptor signal transduction by inhibiting interleukin-1 receptor-associated kinase 4 (IRAK4) offers a new pathway for intervention. Using a pre-clinical NPSLE model, we compare lupus-like B6.MRL-Faslpr (MRL) mice with B6.MRL-Faslpr-IRAK4 kinase-dead (MRL-IRAK4-KD) mice, which are were less prone to ‘general’ lupus-like symptoms. We demonstrate that lupus-prone mice with a mutation in the kinase domain of IRAK4 no longer display typical lupus hallmarks such as splenomegaly, inflammation, production of hormones, and anti-double-stranded (ds)DNA antibody. water maze behavioral testing, which measures contextual associative learning, revealed that mice without functional IRAK4 displayed a recovery in memory acquisition deficits. RNA-seq approach revealed that cytokine and hormone signaling converge on the JAK/STAT pathways in the mouse hippocampus. Ultimately, the targets identified in this work may result in broad clinical value that can fill the significant scientific and therapeutic gaps precluding development of cures for dementia.

Three-Dimensionally Printed Agarose Micromold Supports Scaffold-Free Mouse Ex Vivo Follicle Growth, Ovulation, and Luteinization.

Ex vivo follicle growth is an essential tool, enabling interrogation of folliculogenesis, ovulation, and luteinization. Though significant advancements have been made, existing follicle culture strategies can be technically challenging and laborious. In this study, we advanced the field through development of a custom agarose micromold, which enables scaffold-free follicle culture. We established an accessible and economical manufacturing method using 3D printing and silicone molding that generates biocompatible hydrogel molds without the risk of cytotoxicity from leachates. Each mold supports simultaneous culture of multiple multilayer secondary follicles in a single focal plane, allowing for constant timelapse monitoring and automated analysis. Mouse follicles cultured using this novel system exhibit significantly improved growth and ovulation outcomes with comparable survival, oocyte maturation, and hormone production profiles as established three-dimensional encapsulated in vitro follicle growth (eIVFG) systems. Additionally, follicles recapitulated aspects of in vivo ovulation physiology with respect to their architecture and spatial polarization, which has not been observed in eIVFG systems. This system offers simplicity, scalability, integration with morphokinetic analyses of follicle growth and ovulation, and compatibility with existing microphysiological platforms. This culture strategy has implications for fundamental follicle biology, fertility preservation strategies, reproductive toxicology, and contraceptive drug discovery.