Human leucocytes processed by fast-rate inertial microfluidics retain conventional functional characteristics.

The manufacturing of clinical cellular therapies is a complex process frequently requiring manipulation of cells, exchange of buffers and volume reduction. Current manufacturing processes rely on either low throughput open centrifugation-based devices, or expensive closed-process alternatives. Inertial focusing (IF) microfluidic devices offer the potential for high-throughput, inexpensive equipment which can be integrated into a closed system, but to date no IF devices have been approved for use in cell therapy manufacturing, and there is limited evidence for the effects that IF processing has on human cells. The IF device described in this study was designed to simultaneously separate leucocytes, perform buffer exchange and provide a volume reduction to the cell suspension, using high flow rates with high Reynolds numbers. The performance and effects of the IF device were characterized using peripheral blood mononuclear cells and isolated monocytes. Post-processing cell effects were investigated using multi-parameter flow cytometry to track cell viability, functional changes and fate. The IF device was highly efficient at separating CD14+ monocytes (approx. 97% to one outlet, approx. 60% buffer exchange, 15 ml min-1) and leucocyte processing was well tolerated with no significant differences in downstream viability, immunophenotype or metabolic activity when compared with leucocytes processed with conventional processing techniques. This detailed approach provides robust evidence that IF devices could offer significant benefits to clinical cell therapy manufacture.

Effect of Electronic Health Record Reminders for Routine Immunizations and Immunizations Needed for Chronic Medical Conditions.

BACKGROUND: Immunization reminders in electronic health records (EHR) provide clinical decision support (CDS) that can reduce missed immunization opportunities. Little is known about using CDS rules from a regional immunization information system (IIS) to power local EHR immunization reminders. OBJECTIVE: This study aimed to assess the impact of EHR reminders using regional IIS CDS-provided rules on receipt of immunizations in a low-income, urban population for both routine immunizations and those recommended for patients with chronic medical conditions (CMCs). METHODS: We built an EHR-based immunization reminder using the open-source resource used by the New York City IIS in which we overlaid logic regarding immunizations needed for CMCs. Using a randomized cluster-cross-over pragmatic clinical trial in four academic-affiliated clinics, we compared captured immunization opportunities during patient visits when the reminder was "on" versus "off" for the primary immunization series, school-age boosters, and adolescents. We also assessed coverage of CMC-specific immunizations. Up-to-date immunization was measured by end of quarter. Rates were compared using chi square tests. RESULTS: Overall, 15,343 unique patients were seen for 26,647 visits. The alert significantly impacted captured opportunities to complete the primary series in both well-child and acute care visits (57.6% on vs. 54.3% off, p = 0.001, and 15.3% on vs. 10.1% off, p = 0.02, respectively), among most age groups, and several immunization types. Captured opportunities for CMC-specific immunizations remained low regardless of alert status. The alert did not have an effect on up-to-date immunization overall (89.1 vs. 88.3%). CONCLUSION: CDS in this population improved captured immunization opportunities. Baseline high rates may have blunted an up-to-date population effect. Converting Centers for Disease Control and Prevention (CDC) rules to generate sufficiently sensitive and specific alerts for CMC-specific immunizations proved challenging, and the alert did not have an impact on CMC-specific immunizations, potentially highlighting need for more work in this area.

Managing the COVID-19 Pandemic Using Quality Improvement Principles: A New York City Pediatric Primary Care Experience.

In the setting of COVID-19, pediatric primary care in New York City faced multiple challenges, requiring large-scale practice reorganization. We used quality improvement principles to implement changes to care delivery rapidly. METHODS: Plan-do-study-act cycles were used, based on primary drivers of consolidation, reorganization of in-person and urgent care, telehealth expansion, patient outreach, mental health linkages, team communication, and safety. RESULTS: The average visit volume in pediatrics decreased from 662 per week to 370. Telehealth visits increased from 2 to 140 per week, whereas urgent in-person visits decreased from 350 to 8 per week. Adolescent visits decreased from 57 to 46 per week. Newborn Clinic visits increased from 37 per week to 54. Show rates increased significantly for pediatrics and adolescent (P = 0.003 and P = 0.038, respectively). CONCLUSIONS: Quality improvement methodology allowed for the consolidation of pediatric primary care practices during the first wave of the COVID-19 pandemic, ensuring care for patients while prioritizing safety, evidence-based practices, and available resources.

Who to Test? A Retrospective Study of Lead Testing in High-Risk Children.

BACKGROUND: Nearly all pediatric patients in our setting meet high-risk criteria for lead exposure based on screening recommendations and guidelines. Implementation of screening and testing has been inconsistent. OBJECTIVE: To assess the utility and efficacy of performing universal lead testing between ages 1 and 5 at an urban academic pediatric practice. METHODS: Retrospective review of patients with routine lead testing between 2010 and 2015. Key variables included demographics, serum lead level, and behavioral diagnoses. RESULTS: A total of 6597 serum lead levels from 3274 patients were reviewed. Forty-seven samples (0.7%) from 24 patients (0.7%) were elevated. Of the 24 patients with elevated lead, 75% were identified at age 1 or 2. Sixty-seven percent of patients with first elevated lead level at age 3 or older had a diagnosis of developmental delay. CONCLUSION: Routine testing of high-risk patients yielded minimal specificity in identifying elevated lead levels, especially in patients older than 3 years and without developmental delay.

Design and implementation of an interactive, competency-based pilot pediatric telemedicine curriculum.

During the height of the COVID-19 pandemic, telemedicine visits surged to increase access and maintain continuity of care, while reducing transmission of disease. However, few curricula exist for training residents on how to care for patients via telemedicine, especially in pediatrics. We aimed to create and evaluate an interactive, competency-based pilot curriculum, to meet the urgent need to train residents in telemedicine. The curriculum was developed in 2020 and includes a didactic, cased-based discussions, and direct observation exercise. A model for precepting residents, adhering to new ACGME guidelines, was also created to further engage residents in telemedicine in the outpatient general pediatrics settings. To evaluate the curriculum, we assessed feasibility of a direct observation to provide feedback and we conducted pre and post surveys to assess for changes in residents' self-reported skills in performing telemedicine visits following implementation of the curriculum. 16 residents participated in the curriculum and 15 completed both the pre and post surveys (93%). Residents' self-reported efficacy in performing key components of telemedicine visits, including completion of telemedicine visit (p = 0.023), initiation of visits (p = 0.01), and documentation (p = 0.001) all improved significantly following implementation. Residents' perception of patient satisfaction with telemedicine and personal perception of ease of use of the telemedicine system increased, though neither were statistically significant. Uptake of the direct observation exercise was nearly universal, with all but one resident having a direct observation completed during their ambulatory month. This novel, interactive telemedicine pilot curriculum for residents addresses ACGME competencies and provides residents with a toolkit for engaging in telemedicine.

Integrating Nurse Care Managers in the Medical Home of Children with Special Health Care needs to Improve their Care Coordination and Impact Health Care Utilization.

PURPOSE: There is a rising number of children with special health care needs (CSHCN) in the pediatric medical home and their care coordination is complicated and challenging. We aimed to integrate nurse care managers to coordinate care for such patients, and then evaluate, if this improved health care utilization. DESIGN AND METHODS: This quality improvement project evaluated the impact on CSHCN of the integration of nurse care managers in the pediatric medical home. From October 2015 through February 2019, 673 children received longitudinal care coordination support from a care manager. Health care utilization for primary, subspecialty, emergency department (ED) and inpatient care was reviewed using pre and post design. RESULTS: Three medical home-based nurse care managers were integrated into four pediatric hospital affiliated practices in a large, urban center. The number of ED visits and inpatient admissions were statistically significantly decreased post-intervention (p < 0.05).There was also a decrease in the number of subspecialty visits, but it was close to the threshold of significance (p = 0.054). There was no impact noted on primary care visits. CONCLUSION: This quality improvement project demonstrates that nurse care managers who are integrated into the medical home of CSHCN can potentially decrease the utilization of ED visits and hospital admissions as well as subspecialty visits. PRACTICE IMPLICATIONS: Nurse care managers can play a pivotal role in medical home redesign for the care of CSHCN.

Discriminating Multisystem Inflammatory Syndrome in Children Requiring Treatment from Common Febrile Conditions in Outpatient Settings.

OBJECTIVES: To examine whether patients with multisystem inflammatory syndrome in children (MIS-C) demonstrated well-defined clinical features distinct from other febrile outpatients, given the difficulties of seeing acute care visits during the severe acute respiratory syndrome coronavirus 2 pandemic and the risks associated with both over- and underdiagnosis of MIS-C. STUDY DESIGN: This case-controlled study compared patients diagnosed with and treated for MIS-C at a large urban children's hospital with patients evaluated for fever at outpatient acute care visits during the peak period of MIS-C. Symptomatology and available objective data were extracted. Comparisons were performed using t tests with corrections for multiple comparisons, and multivariable logistic regression to obtain ORs. RESULTS: We identified 44 patients with MIS-C between April 16 and June 10, 2020. During the same period, 181 pediatric patients were evaluated for febrile illnesses in participating outpatient clinics. Patients with MIS-C reported greater median maximum reported temperature height (40°C vs 38.9, P < .0001), and increased frequency of abdominal pain (OR 12.5, 95% CI [1.65-33.24]), neck pain (536.5, [2.23-129,029]), conjunctivitis (31.3, [4.6-212.8]), oral mucosal irritation (11.8, [1.4-99.4]), extremity swelling or rash (99.9, [5-1960]), and generalized rash (7.42, [1.6-33.2]). Patients with MIS-C demonstrated lower absolute lymphocyte (P < .0001) and platelet counts (P < .05) and greater C-reactive protein concentrations (P < .001). CONCLUSIONS: Patients treated for MIS-C due to concern for potential cardiac injury show combinations of features distinct from other febrile patients seen in outpatient clinics during the same period.

A comparison of in vivo viral targeting systems identifies adeno-associated virus serotype 9 (AAV9) as an effective vector for genetic manipulation of Leydig cells in adult mice.

BACKGROUND: Despite the increasing popularity of deliverable transgenics, a robust and fully validated method for targeting Leydig cells, capable of delivering long-term transgene expression, is yet to be defined. OBJECTIVES: We compared three viral vector systems in terms of their cell targeting specificity, longevity of gene expression and impact on targeted cell types when delivered to the interstitial compartment of the mouse testis. MATERIALS & METHODS: We delivered lentiviral, adenoviral and adeno-associated (AAV) viral particles to the interstitial compartment of adult mouse testis. Immunolocalization and stereology were performed to characterize ability of vectors to target and deliver transgenes to Leydig cells. RESULTS: Viral vectors utilized in this study were found to specifically target Leydig cells when delivered interstitially. Transgene expression in lentiviral-targeted Leydig cells was detected for 7 days post-injection before Leydig cells underwent apoptosis. Adenoviral-delivered transgene expression was detected for 10 days post-injection with no evidence of targeted cell apoptosis. We found serotype differences in AAV injected testis with AAV serotype 9 targeting a significant proportion of Leydig cells. Targeting efficiency increased to an average of 59.63% (and a maximum of 80%) of Leydig cells with the addition of neuraminidase during injection. In AAV injected testis sections, transgene expression was detectable for up to 50 days post-injection. DISCUSSION & CONCLUSION: Lentivirus, Adenovirus and Adeno-Associated virus delivery to the testis resulted in key variances in targeting efficiency of Leydig cells and in longevity of transgene expression, but identified AAV9 + Neuraminidase as an efficient vector system for transgene delivery and long-term expression. Simple viral delivery procedures and the commercial availability of viral vectors suggests AAV9 + Neuraminidase will be of significant utility to researchers investigating the genetics underpinning Leydig cell function and holds promise to inform the development of novel therapeutics for the treatment of male reproductive disorders.

A Resident-Led QI Project to Improve Dental Health at a Primary Care Pediatric Practice.

BACKGROUND: Dental caries are the most common chronic condition of childhood and have significant medical, psychological, and financial consequences. The American Academy of Pediatrics (AAP) recommends primary care physicians apply fluoride varnish (FV) every 3 to 6 months from tooth emergence through age 5. OBJECTIVE: Through a resident-led quality improvement (QI) project, we aimed to provide FV to 50% of patients ages 1 through 5 who did not have a dental visit in the preceding 6 months or receive FV elsewhere in the past month. METHODS: From May 2017 through April 2018, we conducted 7 monthly plan-do-study-act cycles to improve our primary outcome measure (FV application), secondary outcome measure (percentage of patients who had routine dental care), and process measure (percentage of dental referrals). Balancing measures included time taken away from other clinical priorities and reimbursement rates. RESULTS: Fluoride varnish application improved from 3.6% to 44% with a 54% peak. The percentage of patients under 6 who had seen a dentist in the past 6 months increased from 30% to 47%. The percentage of dental referrals increased from 17% to 33%. CONCLUSIONS: Application of FV is a quick, cost-effective way for primary care providers to improve dental health. This resident-led QI project increased rates of FV application, dental referrals, and dental visits while meeting ACGME guidelines for experiential learning in QI. By adapting to state-specific guidelines and workflows of each clinic, this QI project could be nationally reproduced to improve adherence to AAP and United States Preventive Services Task Force guidelines.

Androgen Receptor Is Dispensable for X-Zone Regression in the Female Adrenal but Regulates Post-Partum Corticosterone Levels and Protects Cortex Integrity.

Adrenal androgens are fundamental mediators of ovarian folliculogenesis, embryonic implantation, and breast development. Although adrenal androgen function in target tissues are well characterized, there is little research covering the role of androgen-signaling within the adrenal itself. Adrenal glands express AR which is essential for the regression of the X-zone in male mice. Female mice also undergo X-zone regression during their first pregnancy, however whether this is also controlled by AR signaling is unknown. To understand the role of the androgen receptor (AR) in the female adrenal, we utilized a Cyp11a1-Cre to specifically ablate AR from the mouse adrenal cortex. Results show that AR-signaling is dispensable for adrenal gland development in females, and for X-zone regression during pregnancy, but is required to suppress elevation of corticosterone levels post-partum. Additionally, following disruption to adrenal AR, aberrant spindle cell development is observed in young adult females. These results demonstrate sexually dimorphic regulation of the adrenal X-zone by AR and point to dysfunctional adrenal androgen signaling as a possible mechanism in the early development of adrenal spindle cell hyperplasia.

Human Adipose-derived Pericytes Display Steroidogenic Lineage Potential in Vitro and Influence Leydig Cell Regeneration in Vivo in Rats.

Exogenous androgen replacement is used to treat symptoms associated with low testosterone in males. However, adverse cardiovascular risk and negative fertility impacts impel development of alternative approaches to restore/maintain Leydig cell (LC) androgen production. Stem Leydig cell (SLC) transplantation shows promise in this regard however, practicality of SLC isolation/transplantation impede clinical translation. Multipotent human adipose-derived perivascular stem cells (hAd-PSCs) represent an attractive extragonadal stem cell source for regenerative therapies in the testis but their therapeutic potential in this context is unexplored. We asked whether hAd-PSCs could be converted into Leydig-like cells and determined their capacity to promote regeneration in LC-ablated rat testes. Exposure of hAd-PSCs to differentiation-inducing factors in vitro upregulated steroidogenic genes but did not fully induce LC differentiation. In vivo, no difference in LC-regeneration was noted between Sham and hAd-PSC-transplanted rats. Interestingly, Cyp17a1 expression increased in hAd-PSC-transplanted testes compared to intact vehicle controls and the luteinising hormone/testosterone ratio returned to Vehicle control levels which was not the case in EDS + Sham animals. Notably, hAd-PSCs were undetectable one-month after transplantation suggesting this effect is likely mediated via paracrine mechanisms during the initial stages of regeneration; either directly by interacting with regenerating LCs, or through indirect interactions with trophic macrophages.

Relationship of transcriptional markers to Leydig cell number in the mouse testis.

OBJECTIVES: The current study aims to identify markers that would reflect the number of Leydig cells present in the testis, to help determine whether labour-intensive methods such as stereology are necessary. We used our well-characterised Sertoli cell ablation model in which we have empirically established the size of the Leydig cell population, to try to identify transcriptional biomarkers indicative of population size. RESULTS: Following characterisation of the Leydig cell population after Sertoli cell ablation in neonatal life or adulthood, we identified Hsd3b1 transcript levels as a potential indicator of Leydig cell number with utility for informing decision-making on whether to engage in time-consuming stereological cell counting analysis.

Androgen receptor signalling in the male adrenal facilitates X-zone regression, cell turnover and protects against adrenal degeneration during ageing.

Androgens are known to be an essential regulator of male health. Androgen receptor (AR) is widely expressed throughout the adrenal cortex, yet the wider role for androgen signalling in the adrenal remains underexplored. To investigate AR-dependent and AR-independent androgen signalling in the adrenal, we used a novel mouse model with a specific ablation of androgen receptor in the adrenal cortex with or without reduction of circulating androgen levels by castration. Our results describe AR expression in the human and mouse adrenal and highlight that the mouse is a viable model to investigate androgen signalling in the adrenal cortex. We show androgen signalling via AR is required for X-zone regression during puberty. Furthermore, cortex measurements define differences in X-zone morphology depending on whether circulating androgens or AR have been removed. We show androgens promote both cortical cell differentiation and apoptosis but are dispensable for the formation of the definitive cortex. Additionally, investigation of aged mice with AR ablation reveals severe cortex disruption, spindle cell hyperplasia and X-zone expansion. The data described herein demonstrates AR-signalling is required to facilitate X-zone regression, cell clearance and to protect against adrenal degeneration during ageing.

Comparison of central SBP in children estimated from a brachial cuff alone, brachial cuff-calibrated applanation radial tonometry and brachial cuff-calibrated carotid wall-tracking.

OBJECTIVES: We compared the agreement between different techniques to estimate central SBP (cSBP) in children and the relative impact of different methods of measuring peripheral blood pressure (BP). METHODS: A total of 135 children, aged 12.9 ±â€Š3.0 years including 67 boys, 85 with chronic kidney disease were studied. We measured cSBP using radiofrequency ultrasound carotid wall-tracking (Esaote ART.LAB system, a previously validated reference method), transformation of the radial artery pressure waveform obtained by tonometry (SphygmoCor) and a cuff-based system (cBP301; Centron Diagnostics) during a single visit. Carotid and radial tonometric-derived values were calibrated from mean and diastolic values of brachial BP obtained by aneroid sphygmomanometer. Brachial cuff only values were calibrated from the same aneroid sphygmomanometer values and from oscillometric values obtained from the brachial cuff. RESULTS: cSBP values estimated from radial tonometry were closely correlated with those obtained from the carotid (r = 0.959, mean difference -0.61 ±â€Š3.5 mmHg). cSBP values estimated by the brachial cuff only method agreed reasonably well with those obtained from the carotid (r = 0.847, mean difference 5 ±â€Š7.4 mmHg) when calibrated by the same method but when calibrated by oscillometric values from the brachial cuff, agreement was less good (r = 0.659, mean difference 8.7 ±â€Š11.4 mmHg). CONCLUSION: Radial tonometry with a radial-to-central transfer function can be used to estimate cSBP in children with acceptable accuracy when compared with the invasively validated carotid reference method. All methods are subject to errors introduced by calibration from peripheral BP.

Ablation of glucocorticoid receptor in the hindbrain of the mouse provides a novel model to investigate stress disorders.

The hypothalamic-pituitary-adrenal (HPA) axis regulates responses to internal and external stressors. Many patients diagnosed with conditions such as depression or anxiety also have hyperactivity of the HPA axis. Hyper-stimulation of the HPA axis results in sustained elevated levels of glucocorticoids which impair neuronal function and can ultimately result in a psychiatric disorder. Studies investigating Glucocorticoid Receptor (GR/NR3C1) in the brain have primarily focused on the forebrain, however in recent years, the hindbrain has become a region of interest for research into the development of anxiety and depression, though the role of GR signalling in the hindbrain remains poorly characterised. To determine the role of glucocorticoid signalling in the hindbrain we have developed a novel mouse model that specifically ablates hindbrain GR to ascertain its role in behaviour, HPA-axis regulation and adrenal structure. Our study highlights that ablation of GR in the hindbrain results in excessive barbering, obsessive compulsive digging and lack of cage exploration. These mice also develop kyphosis, elevated circulating corticosterone and severe adrenal cortex disruption. Together, this data demonstrates a role for hindbrain GR signalling in regulating stress-related behaviour and identifies a novel mouse model to allow further investigation into the pathways impacting stress and anxiety.

EMR Adaptations to Support the Identification and Risk Stratification of Children with Special Health Care Needs in the Medical Home.

Introduction Children with special health care needs (CSHCN) are a high risk population with complex medical issues and needs. It is challenging to care for them in a busy, pediatric practice without understanding how many exist and how best to allocate resources. EMRs can be adapted to develop registries and stratify patients to promote population health management. Methods Adaptations were made to the EMR in September 2013 to capture CSHCN and the associated risk level during well-child visits prospectively. All physicians were trained on the definition of CSHCN and on risk stratification levels 1, 2, 3A and 3B. An analysis using one-way ANOVA for children ages 0-21, seen between September 1, 2011 and August 31, 2015, who were identified and stratified after September 2013, was conducted to determine utilization patterns on hospital admissions, emergency department (ED), subspecialty, and primary care visits. Results A total of 4687 CSHCN were identified during the study period. Of the CSHCN, 45% were Level 1, 41% Level 2, 7% 3A and 7% 3B. There were significant differences in utilization across the tiers of CSHCN with the highest level of stratification (3B) demonstrating the most hospital admissions and primary care visits. Level 3B and level 3A (unstable) had significantly more ED visits. Additionally, as tiers increased from level 1 to 3B there was an increase in subspecialty provider utilization (p < 0.0001). Discussion The EMR adaptations developed for CSHCN identified the expected number of CSHCN and predicted utilization patterns across primary, subspecialty, ED and in-patient care.

A young testicular microenvironment protects Leydig cells against age-related dysfunction in a mouse model of premature aging.

Testicular Leydig cells (LCs) are the primary source of circulating androgen in men. As men age, circulating androgen levels decline. However, whether reduced LC steroidogenesis results from specific effects of aging within LCs or reflects degenerative alterations to the wider supporting microenvironment is unclear; inability to separate intrinsic LC aging from that of the testicular microenvironment in vivo has made this question difficult to address. To resolve this, we generated novel mouse models of premature aging, driven by CDGSH iron sulfur domain 2 ( Cisd2) deletion, to separate the effects of cell intrinsic aging from extrinsic effects of aging on LC function. At 6 mo of age, constitutive Cisd2-deficient mice display signs of premature aging, including testicular atrophy, reduced LC and Sertoli cell (SC) number, decreased circulating testosterone, increased luteinizing hormone/testosterone ratio, and decreased expression of steroidogenic mRNAs, appropriately modeling primary testicular dysfunction observed in aging men. However, mice with Cisd2 deletion (and thus premature aging) restricted to either LCs or SCs were protected against testicular degeneration, demonstrating that age-related LCs dysfunction cannot be explained by intrinsic aging within either the LC or SC lineages alone. We conclude that age-related LC dysfunction is largely driven by aging of the supporting testicular microenvironment.-Curley, M., Milne, L., Smith, S., Jørgensen, A., Frederiksen, H., Hadoke, P., Potter, P., Smith, L. B. A Young testicular microenvironment protects Leydig cells against age-related dysfunction in a mouse model of premature aging.

Leukemia Inhibitory Factor-Receptor is Dispensable for Prenatal Testis Development but is Required in Sertoli cells for Normal Spermatogenesis in Mice.

Leukemia inhibitory factor (LIF), a pleiotropic cytokine belonging to the interleukin-6 family, is most often noted for its role in maintaining the balance between stem cell proliferation and differentiation. In rodents, LIF is expressed in both the fetal and adult testis; with the peritubular myoid (PTM) cells thought to be the main site of production. Given their anatomical location, LIF produced by PTM cells may act both on intratubular and interstitial cells to influence spermatogenesis and steroidogenesis respectively. Indeed, the leukemia inhibitory factor receptor (LIFR) is expressed in germ cells, Sertoli cells, Leydig cells, PTM cells and testicular macrophages, suggesting that LIF signalling via LIFR may be a key paracrine regulator of testicular function. However, a precise role(s) for testicular LIFR-signalling in vivo has not been established. To this end, we generated and characterised the testicular phenotype of mice lacking LIFR either in germ cells, Sertoli cells or both, to identify a role for LIFR-signalling in testicular development/function. Our analyses reveal that LIFR is dispensable in germ cells for normal spermatogenesis. However, Sertoli cell LIFR ablation results in a degenerative phenotype, characterised by abnormal germ cell loss, sperm stasis, seminiferous tubule distention and subsequent atrophy of the seminiferous tubules.

Sertoli Cells Modulate Testicular Vascular Network Development, Structure, and Function to Influence Circulating Testosterone Concentrations in Adult Male Mice.

The testicular vasculature forms a complex network, providing oxygenation, micronutrients, and waste clearance from the testis. The vasculature is also instrumental to testis function because it is both the route by which gonadotropins are delivered to the testis and by which T is transported away to target organs. Whether Sertoli cells play a role in regulating the testicular vasculature in postnatal life has never been unequivocally demonstrated. In this study we used models of acute Sertoli cell ablation and acute germ cell ablation to address whether Sertoli cells actively influence vascular structure and function in the adult testis. Our findings suggest that Sertoli cells play a key role in supporting the structure of the testicular vasculature. Ablating Sertoli cells (and germ cells) or germ cells alone results in a similar reduction in testis size, yet only the specific loss of Sertoli cells leads to a reduction in total intratesticular vascular volume, the number of vascular branches, and the numbers of small microvessels; loss of germ cells alone has no effect on the testicular vasculature. These perturbations to the testicular vasculature leads to a reduction in fluid exchange between the vasculature and testicular interstitium, which reduces gonadotropin-stimulated circulating T concentrations, indicative of reduced Leydig cell stimulation and/or reduced secretion of T into the vasculature. These findings describe a new paradigm by which the transport of hormones and other factors into and out of the testis may be influenced by Sertoli cells and highlights these cells as potential targets for enhancing this endocrine relationship.