Abstracts from the Abstracts from the NIH Office of Research on Women's Health 2021 Annual BIRCWH Meeting:Building Interdisciplinary Research Careers in Women's Health December 13, 2021
2021; Mary Ann Liebert, Inc.; Volume: 30; Issue: 12 Linguagem: Inglês
10.1089/jwh.2021.29039.abstracts
ISSN1931-843X
Tópico(s)Sex and Gender in Healthcare
ResumoJournal of Women's HealthAhead of Print AbstractsFree AccessAbstracts from the NIH Office of Research on Women's Health 2021 Annual BIRCWH Meeting:Building Interdisciplinary Research Careers in Women's Health December 13, 2021Published Online:1 Oct 2021https://doi.org/10.1089/jwh.2021.29039.abstractsAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail Building Interdisciplinary Research Careers in Women's Health (BIRCWH)Introduction to the Scientific Abstracts for the 2021 Annual BIRCWH MeetingLisa Begg, Dr.P.H., RN1The Building Interdisciplinary Research Careers in Women's Health (BIRCWH) Program celebrated its twentieth anniversary in 2020 and continues to produce highly qualified and successful junior investigators. The BIRCWH program was created by the Office of Research on Women's Health (ORWH), National Institutes of Health (NIH) and several NIH institutes and centers in 2000. The program continues to utilize an institutional mentored research and career development grant program that has increased the number and skills of junior faculty called Scholars, who recently completed clinical training or postdoctoral fellowships.The BIRCWH program supports the ORWH mission and advances its goal to promote the independent scientific careers for a diverse, and robust workforce to advance science for the health of women, and where appropriate, the use of both sexes to better understand the influence of sex as a variable for health and disease.When the BIRCWH Program was originally created, most of the scientific abstracts focused on reproductive health research. Over the years, however, the abstract topics have greatly expanded across many areas of science. In terms of the 2021 BIRCWH abstracts, eleven abstracts focus on sex and gender influences that enhance research on the health of women. Some of these abstracts have a basic science focus while others center on clinical research or public health. For example, one abstract reports on sex‐based gene expression, while another evaluates the association between telomere length and early‐midlife memory function ‐ the impact of sex, reproductive aging and hypertension. A clinical study involving Kenyan adults looked at sex differences in inflammation and immune activation among antiretroviral‐treated people with or without HIV.In addition to abstracts that have a basic or clinical focus are those covering public health, and health disparities research. Within specialty areas, reproductive health topics have the next highest number of abstracts, followed by cancer research, cardiovascular research, and neuroscience research.In recent years, the abstracts have described complex research topics such as machine learning to identify predictive lipid markers of cardiovascular disease risk. There have also been an increasing number of public health topics accepted for the annual BIRCWH meetings, including using data from more than two million births to estimate the effect of the timing of the earned income tax credit refunds on perinatal outcomes. Health disparity abstract topics include a study of food insecurity and social isolation among women during the Covid‐19 pandemic.We invite the reader to review all of the BIRCWH abstracts included in this issue to see the depth of topics which include research across the lifespan in civilian populations as well as military and Veteran groups of women and men.The career development associated with these BIRCWH abstracts is built around three pillars: interdisciplinary research, mentoring, and career development. Interdisciplinary science teams work to advance fundamental understanding and solve problems that those from a single discipline cannot. The interdisciplinary research can be basic, translational, behavioral, clinical, and/or health‐services research relevant to the health of women. Most BIRCWH Scholars move on to obtain independent NIH grant funding following their participation in the BIRCWH Program.The interdisciplinary mentoring teams are essential to the BIRCWH Program, with a team‐based approach for mentoring BIRCWH Scholars. These teams include mentors from diverse disciplines to carry out interdisciplinary projects. Team members may include individuals from medical, dentistry, pharmacy, nursing, veterinary medicine, biotechnology, social sciences, anthropology, genetics, public health, and other disciplines representing different perspectives and areas of expertise. These teams come together to collaborate as a unit, with the common goal of supporting a BIRCWH Scholar in the transition from trainee to independent researcher.The 2021 Annual BIRCWH meeting will be held virtually on December 13, 2021. There will be a plenary session in the morning, with two special talks ‐ the Ruth L. Kirschstein Memorial Lectureship, and the Legacy of Leadership lecture. There will also be three Podium talks for the top Scholar abstracts – these abstracts are listed first in the abstract file below. In the afternoon, there will be a virtual poster session with all of the abstracts. The published abstracts below will form the basis of the virtual poster session. More detailed information about this meeting and the BIRCWH program can be found on the ORWH website, www.nih.gov/womenDr. Begg is the Senior Research Program Officer in the NIH Office of Research on Women's Health, overseeing the BIRCWH Program. For further information about the BIRCWH Program and the 2021 Annual BIRCWH Meeting, please contact Dr. Begg at, beggl@od.nih.gov2021 BIRCWH Podium AbstractsO‐1. Global Lipidomics Identifies Novel Circulating Markers of CVD Risk in African American and Caucasian WomenJudith Simcox (presenting author),1 Raghav Jain,1 Chris Coe,2 Camille King,1 Kristen Malecki,3 Andy Bersh,3 Carol Ryff21Department of Biochemistry, University of Wisconsin–Madison; 2Department of Psychology, University of Wisconsin–Madison; 3Department of Population Health Sciences, University of Wisconsin–MadisonBackground: Cardiovascular disease (CVD) is the leading cause of mortality for women in the US. Women with dyslipidemia have an increased risk of CVD. The parameters of dyslipidemia have primarily been defined using Caucasian male populations.Objective: Current lipid markers of dyslipidemia—including high‐density lipoprotein (HDL), low‐density lipoprotein (LDL), and triglycerides—have been shown to be poor predictors of CVD risk in African American populations. We aim to identify markers of dyslipidemia in African American populations that better predict risk and development of CVD.Methods: Untargeted lipidomics (total lipid number) was performed on sera from middle‐aged African American and Caucasian women (n = 872) using samples from the Midlife in the United States (MIDUS) human population study. Machine learning was used to identify predictive lipid markers of CVD risk. Findings were validated using an independent cohort of women (n = 200).Results: We identified unique and shared signatures of CVD in women based on race. Arachidonic acid containing lipids is positively correlated with elevated blood pressure and worsened cardiovascular stress test results. Because these lipids are important in inflammatory signaling, we also assessed interleukin‐6 and C‐reactive protein. Through machine learning, we were able to determine that markers of inflammation and inflammatory lipids were predictive of CVD in both Caucasian and African American women.Conclusions: Regardless of class, lipid species containing arachidonic acid were increased in the circulation of women with hypertension. We propose the consideration of an inflammatory marker panel that includes arachidonic acid to assess CVD risk in women.O‐2. Gender‐Based Differences in Prehospital Care for Suspected StrokeLayne Dylla (presenting author),1 John D. Rice,2 Paco S. Herson,3 Sharon N. Poisson,4 Adit A. Ginde11Department of Emergency Medicine, University of Colorado School of Medicine ; 2Department of Biostatistics and Informatics, Colorado School of Public Health; 3Department of Anesthesiology, University of Colorado School of Medicine; 4Department of Neurology, University of Colorado School of MedicineBackground: Men and women differ in their in‐hospital stroke treatment and outcomes. However, it is unclear whether these discrepancies exist in the prehospital setting, the first health care provider contact for most stroke patients.Objective: This study characterizes nationwide emergency medical services (EMS) practices for potential stroke patients and assesses for gender‐based differences in EMS care.Methods: Patients and associated EMS practices with an EMS primary impression of stroke from the 2019 National EMS Information System (NEMSIS) Version 3 Public‐Release Database were characterized using descriptive statistics. We assessed compliance with 8 American Stroke Association (ASA) recommendations for prehospital care of suspected stroke patients. Guideline‐concordant care is defined as compliance with all 8 ASA metrics. Multivariable logistic regression modeled the association between the primary outcome (guideline‐concordant care) and gender while controlling for potential confounders.Results: Of 304,517 EMS encounters with suspected stroke, 52% (157,981) involved women. Compliance with ASA recommendations ranged from 32% of encounters completing a 12‐lead electrocardiogram to 77% of encounters having a dispatch time of less than 90 seconds. Only 447 (0.15%) of these encounters were fully compliant. Women had 19% decreased odds of receiving guideline‐concordant care compared with men after adjusting for confounders (OR, 0.81; 95% CI, 0.70–0.94).Conclusions: Despite increasing awareness of the role of EMS and the sex‐based differences in stroke, there remains a wide range of compliance with ASA guidelines for care of suspected stroke patients. While few patients receive care completely concordant with recommendations, women are less likely to receive fully guideline‐concordant care than men.O‐3. Ubiquitination of Zika Virus Envelope Protein Promotes Embryonic DamageMaria I. Giraldo (presenting author),1 Maria Gonzalez‐Orozco,1 Scott Weaver,1,2 Pei‐Yong Shi,2,3 Ricardo Rajsbaum1,21Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston; 2Institute for Human Infections and Immunity, University of Texas Medical Branch at Galveston; 3Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at GalvestonBackground: Zika virus (ZIKV) is transmitted to humans by mosquito vectors. Infections in pregnant women are of major concern because the infections have been associated with microcephaly in newborns. We recently reported that ubiquitination on the ZIKV envelope (E) protein is important for virus attachment to host cells, but its role during pregnancy is unknown.Objective: To identify the molecular mechanisms by which ZIKV causes damage during pregnancy.Methods: We compared pathogenicity between wild‐type Zika virus (ZIKV WT) and a mutant virus that lacks ubiquitination on E‐K281R in a mouse pregnancy model. Pregnant mice were infected with ZIKV WT or E‐K281R, and at embryonic day 18.5, they were euthanized for analysis of the embryos. Viral loads and global gene expression were determined by plaque assay, RNA sequencing, and quantitative polymerase chain reaction.Results: Pregnant mice infected with the E‐K281R mutant virus showed less weight loss than pregnant mice infected with ZIKV WT. WT and E‐K281R viral loads were similar in the spleens of infected mothers. Strikingly, infection with WT virus caused a significant reduction in fetus size compared with mock‐treated controls, whereas the E‐K281R virus did not. ZIKV E‐K281R titers in the placenta and fetal heads were significantly lower than ZIKV WT titers in the placenta and fetal heads. We also identified changes in expression levels of genes associated with brain development and microcephaly in embryos infected with WT as compared with mock or the E‐ K281R.Conclusions: Our data suggest that lack of ubiquitination on E‐K281 reduces viral pathogenesis in the embryos of infected mothers and that ubiquitination specifically on E‐K281 may be important in embryonic damage.2021 BIRCWH Poster AbstractsDuke University1. Associating Cognitive Processes with Question‐Asking After Right Hemisphere Brain DamageJamila M. Minga (presenting author),1,2 Melissa D. Stockbridge,3 Davida Fromm,4 Adam Jacks,5 Simon Davis,5 Jenni Groh,6 Argye Hillis31Department of Communication Sciences and Disorders, North Carolina Central University; 2Department of Head and Neck Surgery & Communication Sciences, Duke University; 3Department of Neurology, Johns Hopkins University School of Medicine; 4Department of Psychology, Carnegie Mellon University; 5Department of Allied Health Sciences, University of North Carolina at Chapel Hill; 6Department of Neurology, Duke University; 7Department of Psychology and Neuroscience, Duke UniversityBackground: Right hemisphere brain damage (RHD) can cause challenges with information gathering. Cognitive processes aid in implicit and explicit information gathering, yet the relationship between these processes and question‐asking, the most explicit avenue of information‐gathering, has not been explored for therapeutic considerations.Objective: To determine whether associations exist between cognitive domains and questions produced during a conversation task.Methods: Fifteen adults with RHD (mean±SD; 52 ± 9.5 years; 48% female) and 15 healthy controls (45 ± 11 years; 81% female) were assessed for attention, memory, executive functioning (EF), visuospatial skills, and language domains using the Cognitive Linguistic Quick Test (CLQT) and participated in a 5‐minute “first encounter” conversation. Questions produced during the conversation were tallied and coded by type: polar (yes/no), content (wh‐), and alternative (A or B). Groups were compared on total questions used and CLQT domain scores; associations were computed between cognitive domain scores and question types using Kendall's τ.Results: The RHD group asked half as many questions (median[max], 7[15]) as healthy controls (16[31]). Three CLQT domain scores were significantly lower for the RHD group: EF (t[df], 2.13[28]; P = 0.04), visuospatial (2.97[19.21]; P = 0.006), and attention (2.34[15.44]; P = 0.03). For the RHD group, there was a significant correlation between EF and total questions (τ = 0.44, P < 0.01), driven by content (τ = 0.52, P < 0.05) and polar (τ = 0.45, P < 0.05) questions. These relationships were not significant for controls.Conclusions: EF, attention, and visuospatial capabilities may contribute to question‐asking behaviors, with EF potentially playing a critical role in question‐asking by people with RHD. A larger RHD sample will help determine whether targeting EF skills can increase question‐asking.2. Leakage from Accountable Care Organizations Among Gynecologic Cancer Patients: Prevalence and PredictorsHaley A. Moss (presenting author),1,2 Oyomoare Osazuwa‐Peters,3 Brystana G. Kaufman,3 Michaela A. Dinan,4 Evan R. Myers,2 Laura J. Havrilesky1,21Duke Cancer Institute, Duke University; 2Department of Obstetrics and Gynecology, Duke University; 3Department of Population Health, Duke University; 4Department of Chronic Disease Epidemiology, Yale UniversityBackground: An accountable care organization (ACO) is a network of providers that share financial and medical responsibility for a group of patients. “Leakage” of care outside of a patient's assigned ACO may contribute to difficulties for providers to control costs and quality of care.Objective: To identify the incidence and factors that predict gynecologic cancer care outside of a patient's assigned ACO.Methods: This retrospective cohort study assessed Medicare beneficiaries enrolled in an ACO in the Centers for Medicare & Medicaid Services' 5% Limited Data Set who were diagnosed with a gynecologic malignancy from 2013 to 2018. Proportion of cancer care outside of the ACO (i.e., leakage) was assessed. A log binomial regression model was used to determine patient and ACO factors related to leakage.Results: Of the 1,230 patients included in our study, 28.1% of patients received cancer‐ directed care outside of the assigned ACO. Leakage was associated with Black race (RR, 1.52; 95% CI, 1.14–2.03), longer travel distance to a hospital (RR, 1.25; 95% CI, 1.01–1.54), and highest‐quintile median household income (RR, 1.76; 95% CI, 1.26–2.46). Leakage was inversely related to ACO size (RR, 0.97; 95% CI, 0.95–0.98) and a larger number of subspecialty providers (RR, 0.91; 95% CI, 0.87–0.96).Conclusions: Leakage of cancer care outside of a gynecologic cancer patient's assigned ACO is common. ACOs may improve care coordination and prevent leakage by forming larger health systems and increasing access to subspecialists. Future directions include an assessment of costs and differences in leakage rates by patients diagnosed with other malignancies, such as prostate cancer.3. Physical Activity Levels of Women Attending Community Health ClinicsKatelyn M. Holliday (presenting author),1 Laura Fish,1 Truls Østbye,1 Daniela Sotres‐Alvarez,2 Dianne S. Ward31Department of Family Medicine and Community Health, Duke University; 2Department of Biostatistics, University of North Carolina at Chapel Hill; 3Department of Nutrition, University of North Carolina at Chapel HillBackground: Many women do not meet the physical activity guidelines of 150 minutes of moderate to vigorous physical activity (MVPA) each week.Objectives: This study aims to gather information on barriers to and facilitators of physical activity, as well as usual physical activity behaviors, among 60 women ages 20–40 recruited from two community health clinics in Durham, NC.Methods: Women wore an Actigraph GT9X Link accelerometer during waking hours for 2 weeks. They were asked not to change their usual behavior and received no feedback from the accelerometers. Non‐wear periods were identified with an algorithm and removed. Valid wear days were defined as days with at least 10 hours of accelerometer wear. Minutes of lower‐intensity lifestyle physical activity (LPA; ≥760 counts/minute) and MVPA (≥2,020 counts/minute) were identified. The percentage of women meeting physical activity guidelines was calculated.Results: Thus far, 17 women (mean age 31 years; 24% Hispanic/Latina, 18% Non‐Hispanic Black, 59% Non‐Hispanic White) have worn the accelerometers for an average of 13 10‐hour days. Each participant's average minutes of LPA per week ranged from 152 to 1,309 (median = 556). In contrast, their average minutes of higher‐intensity MVPA ranged from 7 to 713 (median = 200), with 60% of women meeting physical activity guidelines.Conclusions: Further data collection will allow comparison of physical activity levels by sociodemographic characteristics and clinic. These data, along with survey and interview data on barriers and facilitators of physical activity, will aid development of intervention materials to increase physical activity levels of women attending these and other community health clinics.Emory University4. Estradiol and Treatment Response in Prolonged Exposure Therapy for Women with PTSDJessica L. Maples‐Keller (presenting author),1 Vasiliki Michopoulos,1,2 Jennifer Stevens,1 Carly Yasinski,1 Mansi Mehta,1 Seth D. Norrholm,3 Tanja Jovanovic,3 Sheila A.M. Rauch,1,4 Barbara O. Rothbaum11Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine; 2Yerkes National Primate Research Center; 3Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine; 4Atlanta VA Health Care SystemBackground: Prolonged exposure (PE) is a first‐line treatment for post‐traumatic stress disorder (PTSD). However, a subset of patients demonstrates suboptimal treatment response. The extant literature has not identified consistent clinical variables that predict treatment response, indicating that biological factors may be important to consider. Fear extinction is a well‐characterized translational model of PTSD. Women demonstrate twice the prevalence of PTSD, and animal models indicate that low estrogens are associated with deficits in fear extinction retention (Milad et al., 2009). Low estradiol is associated with extinction learning deficits in women with PTSD (Glover et al., 2012). Fear extinction is the theoretical foundation of PE, indicating that estradiol may be a relevant factor in PE outcomes.Objective: To evaluate the impact of estradiol on PE outcomes in women with PTSD.Methods: Women veterans (n = 101, average age = 40.66, SD = 9.45) engaged in a 2‐week PE program with daily imaginal and in vivo exposure sessions and completed a blood draw pretreatment.Results: PE demonstrated a large effect size (d = 1.30) in reduction in self‐reported PTSD symptoms, with 77.6% of participants demonstrating a clinically significant reduction in symptoms, indicating variability in response and a potential to identify factors that may predict suboptimal response. Estradiol assays will be completed by July 2021 to investigate the hypothesis that women with low estradiol at pretreatment will demonstrate less reduction in PTSD symptoms from pretreatment to posttreatment in PE.Conclusions: Results may inform the ability to identify women at risk for low PE response to inform potential augmentation strategies.5. Reproductive Aging in Women Seeking In Vitro FertilizationAnna K. Knight (presenting author),1 Heather S. Hipp,2 Sina Abhari,2 Sabrina Gerkowicz,3 Quinton S. Katler,2 Laurie J. McKenzie,4 Weirong Shang,2 Jessica J. Spencer,2 Alicia K. Smith11Department of Gynecology and Obstetrics, Division of Research, Emory University; 2Department of Gynecology and Obstetrics, Division of Reproductive Endocrinology and Infertility, Emory University; 3IVF MD, Boca Raton, Florida; 4Division of Reproductive Endocrinology and Infertility, Baylor College of MedicineBackground: Less than 33% of in vitro fertilization (IVF) cycles result in a live birth, and success rates fall rapidly with advancing maternal age, likely because of declines in oocyte quantity and quality. However, such declines are not uniform among all women of the same chronological age. DNA methylation–based predictors of reproductive aging may allow us to further understand factors contributing to both IVF success and long‐term maternal health.Objectives: To identify associations between reproductive aging and both ovarian reserve characteristics and IVF cycle outcomes.Methods: Follicular fluid samples were collected from women undergoing IVF at the time of oocyte retrieval. Samples were processed via centrifugation, and granulosa cell DNA was extracted and assayed with the MethylationEPIC array (n = 70). DNA methylation age (GrimAge) and age acceleration were calculated using the method described by Steve Horvath, PhD, of UCLA. Linear regression was used to determine associations between age acceleration and cycle characteristics and outcomes.Results: GrimAge was highly correlated with chronological age (t = 9.3, P = 9.6e–14), and its residuals (age acceleration) were normally distributed. Age acceleration is associated with ovarian reserve measures (antral follicle count: t = −3.6, P = 0.007; anti‐müllerian hormone levels: t = −3.1, P = 0.002), the number of total (t = −3.3, P = 0.002) and mature (t = −3.1, P = 0.003) oocytes retrieved, and successful fertilization (t = −2.1, P = 0.04).Conclusion: Our data suggest women with increased reproductive age acceleration have lower ovarian reserve at the start of IVF and have poorer cycle outcomes. Future studies are needed to determine whether advanced reproductive aging is an early indicator of other age‐related health problems.Harvard, Brigham and Women's Hospital, and Massachusetts General Hospital6. Association Between Telomere Length and Early‐Midlife Memory Function: Impact of Sex, Reproductive Aging, and HypertensionKyoko Konishi (presenting author),1 Emily G. Jacobs,2 Brianna Smith,1 Sarah Aroner,1 Hannah Shields,1 Immaculata De Vivo,3,4 Nikos Makris,1 Anne Remington,1 Harlyn Aizley,1 Jill M. Goldstein1,51Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School; 2Department of Psychological and Brain Sciences, University of California, Santa Barbara; 3Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School; 4Department of Epidemiology, Harvard T.H. Chan School of Public Health; 5Department of Medicine, Harvard Medical SchoolBackground: Shorter telomere length (TL) is an important cellular marker of biological aging that is associated with cognitive decline, hypertension, and atrophy of the hippocampus, a key region in the memory circuitry. Estradiol, a sex steroid hormone that declines in menopause, regulates TL by decreasing oxidative stress and upregulating enzymes that repair telomere shortening.Objective: Here, we assessed the impact of TL—in relation to sex, reproductive status, and hypertension—on the volume of memory circuitry regions in the brain and memory performance in early midlife.Methods: Participants (n = 212, 106 women and 106 men; ages 45–55) underwent MRI and neuropsychological assessments of memory. Leukocyte TL was determined by extracting genomic DNA.Results: In women, shorter TL was associated with poor memory performance (β=0.19, pFDR=0.03), and in postmenopause, it was further related to smaller right hippocampal volume (β=111.92, pFDR=0.04). In men, longer TL tended to be associated with larger volume in the parahippocampus (β = 127.86, pFDR=0.08) and anterior cingulate cortex (β=271.64, pFDR=0.08). We also found that shorter TL was associated with hypertension in midlife (β = −0.41, P = 0.007), which in turn was related to poor memory performance in men (β = −1.85, P = 0.0006) and women (β = −1.84, P = 0.005).Conclusions: Results demonstrate that longer TL is associated with better memory function and larger volume in memory circuitry regions in early midlife, an effect that differs by sex and reproductive status. Further, findings suggest that TL may partially mediate the relationship between cardiovascular health and cognitive function in later life and may serve as an early biomarker of sex‐dependent brain and cardiovascular abnormalities in early midlife.7. Sex‐Biased Gene Expression in Humans: Using Gender Transition to Define the Roles of Sex Hormones and Sex Chromosomes on a Single‐Cell LevelRebecca M. Harris (presenting author),1,2 Emily Jackson,1 Stephanie Zhang,1 Troy Whitfield,1 Helen Skaletsky,1 Jasmina Cesko,2 Bingrun Liu,1 Yee‐Ming Chan,2 David C. Page11Whitehead Institute, 2Division of Endocrinology, Boston Children's HospitalBackground: Healthy traits and diseases differ between women and men. Sex hormones and sex chromosomes mediate these differences through sex‐biased gene expression (i.e., differences in gene expression between females and males).Objectives: To determine the independent and interdependent contributions of sex hormones and sex chromosomes to sex‐biased gene expression in humans.Methods: We conducted a pilot study comparing single‐cell RNA sequencing (scRNA‐seq) data from peripheral blood mononuclear cells (PBMCs) from transgender individuals on estradiol or testosterone for at least 1 year and cisgender controls. PBMCs were isolated from 25 subjects (n = 6 transgender males, n = 6 transgender females, n = 6 cisgender males, and n = 7 cisgender females). RNA‐seq was completed using the 10X Genomics platform. A quality control pipeline was created using numbers of expressed genes, unique molecular identifiers, percentage of mitochondrial gene expression, and doublet scores. Cell types were identified via dimensionality reduction using uniform manifold approximation and projection. Differential gene expression was analyzed using pseudobulk (DESeq2) and mixed effects (MAST) models.Results: A total of 19,443 genes from 110,776 cells were sequenced. Fourteen cell populations were identified. Gene expression between samples within a cell type was highly correlated (r > 0.92). A total of 379 differentially expressed genes were identified (23 X chromosomes, 4 Y chromosomes, and 352 autosomal genes); 96 genes were differentially regulated in more than 1 cell type.Conclusions: Over 1.5% of the genome is differentially regulated by the sex hormones and sex chromosomes; the majority of differentially expressed genes are autosomal.8. The Impact of Makorin RING Finger Protein 3 Overexpression in the Arcuate Nucleus of Postpubertal Female MiceStephanie A. Roberts (presenting author),1,2 Han Kyeol Kim,1 Sidney Alcantara,1 Rona S. Carroll,1 Ursula B. Kaiser11Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital; 2Division of Endocrinology, Boston Children's HospitalBackground: MKRN3, an inhibitor of the KISS1 and TAC3 promoters in the hypothalamic arcuate nucleus, is an important player in the age of menarche and etiology of central precocious puberty. However, its potential role in delayed puberty and/or hypogonadism is not defined.Objectives: As neonatal hypothalamic overexpression of MKRN3 leads to delayed puberty in female mice, this study aimed to explore the effects of MKRN3 overexpression in postpubertal female mice.Methods: Adult wild‐type female C57BL6 mice were stereotaxically injected into the arcuate nucleus of the hypothalamus with a recombinant adeno‐associated virus (rAAV‐MKRN3‐IRES‐EGFP; n = 12) to overexpress MKRN3 or with a control virus (rAAV‐EGFP; n = 9).Results: Daily vaginal smears collected 5 weeks post‐surgery showed that rAAV‐MKRN3‐injected mice spent more time (62.7%) in diestrus than controls (41.3%). The gain in body weight was similar for both groups (0.3–0.4g per week). Pre‐surgery basal luteinizing hormone (LH) levels did not differ b
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