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Stem cells reside in a niche, a local environment whose cellular and molecular complexity is still being elucidated. In ovaries, germline stem cells depend on cap cells for self-renewing signals and physical attachment. Germline stem cells also contact the anterior escort cells, and here we report that anterior escort cells are absolutely required for germline stem cell maintenance. When escort cells die from impaired Wnt signaling or expression, the loss of anterior escort cells causes loss of germline stem cells. Anterior escort cells function as an integral niche component by promoting DE-cadherin anchorage and by transiently expressing the Dpp ligand to promote full-strength BMP signaling in germline stem cells. Anterior escort cells are maintained by Wnt6 ligands produced by cap cells; without Wnt6 signaling, anterior escort cells die leaving vacancies in the niche, leading to loss of germline stem cells. Our data identify anterior escort cells as constituents of the germline stem cell niche, maintained by a cap cell-produced Wnt6 survival signal.
© 2018. Published by The Company of Biologists Ltd.
Adipocytes have key endocrine roles, mediated in large part by secreted protein hormones termed adipokines. The adipokine adiponectin is well known for its role in sensitizing peripheral tissues to insulin, and several lines of evidence suggest that adiponectin might also modulate stem cells/precursors. It remains unclear, however, how adiponectin signaling controls stem cells and whether this role is secondary to its insulin-sensitizing effects or distinct. Drosophila adipocytes also function as an endocrine organ and, although no obvious adiponectin homolog has been identified, Drosophila AdipoR encodes a well-conserved homolog of mammalian adiponectin receptors. Here, we generate a null AdipoR allele and use clonal analysis to demonstrate an intrinsic requirement for AdipoR in germline stem cell (GSC) maintenance in the Drosophila ovary. AdipoR null GSCs are not fully responsive to bone morphogenetic protein ligands from the niche and have a slight reduction in E-cadherin levels at the GSC-niche junction. Conversely, germline-specific overexpression of AdipoR inhibits natural GSC loss, suggesting that reduction in adiponectin signaling might contribute to the normal decline in GSC numbers observed over time in wild-type females. Surprisingly, AdipoR is not required for insulin sensitization of the germline, leading us to speculate that insulin sensitization is a more recently acquired function than stem cell regulation in the evolutionary history of adiponectin signaling. Our findings establish Drosophila female GSCs as a new system for future studies addressing the molecular mechanisms whereby adiponectin receptor signaling modulates stem cell fate.
Copyright © 2015 Elsevier Inc. All rights reserved.
Inward rectifier potassium (Kir) channels play essential roles in regulating diverse physiological processes. Although Kir channels are encoded in mosquito genomes, their functions remain largely unknown. In this study, we identified the members of the Anopheles gambiae Kir gene family and began to investigate their function. Notably, we sequenced the A. gambiae Kir1 (AgKir1) gene and showed that it encodes all the canonical features of a Kir channel: an ion pore that is composed of a pore helix and a selectivity filter, two transmembrane domains that flank the ion pore, and the so-called G-loop. Heterologous expression of AgKir1 in Xenopus oocytes revealed that this gene encodes a functional, barium-sensitive Kir channel. Quantitative RT-PCR experiments then showed that relative AgKir1 mRNA levels are highest in the pupal stage, and that AgKir1 mRNA is enriched in the adult ovaries. Gene silencing of AgKir1 by RNA interference did not affect the survival of female mosquitoes following a blood meal, but decreased their egg output. These data provide evidence for a new role of Kir channels in mosquito fecundity, and further validates them as promising molecular targets for the development of a new class of mosquitocides to be used in vector control.
Copyright © 2014 Elsevier Ltd. All rights reserved.
We previously showed that asunder (asun) is a critical regulator of dynein localization during Drosophila spermatogenesis. Because the expression of asun is much higher in Drosophila ovaries and early embryos than in testes, we herein sought to determine whether ASUN plays roles in oogenesis and/or embryogenesis. We characterized the female germline phenotypes of flies homozygous for a null allele of asun (asun(d93)). We find that asun(d93) females lay very few eggs and contain smaller ovaries with a highly disorganized arrangement of ovarioles in comparison to wild-type females. asun(d93) ovaries also contain a significant number of egg chambers with structural defects. A majority of the eggs laid by asun(d93) females are ventralized to varying degrees, from mild to severe; this ventralization phenotype may be secondary to defective localization of gurken transcripts, a dynein-regulated step, within asun(d93) oocytes. We find that dynein localization is aberrant in asun(d93) oocytes, indicating that ASUN is required for this process in both male and female germ cells. In addition to the loss of gurken mRNA localization, asun(d93) ovaries exhibit defects in other dynein-mediated processes such as migration of nurse cell centrosomes into the oocyte during the early mitotic divisions, maintenance of the oocyte nucleus in the anterior-dorsal region of the oocyte in late-stage egg chambers, and coupling between the oocyte nucleus and centrosomes. Taken together, our data indicate that asun is a critical regulator of dynein localization and dynein-mediated processes during Drosophila oogenesis.
Copyright © 2013 Elsevier Inc. All rights reserved.
More than 4 million menopausal women are from ethnic minority groups. Over the past 25 years, recognition of the importance of social, emotional, and physical changes of midlife to women's long-term health and well-being has emerged. Multiple factors influence how a woman perceives menopausal changes and what she addresses as associated symptoms. Factors such as educational level to socioeconomic status, health-related factors, stress, and marital status influence these choices. Increasingly, researchers are reporting on the impact of race and ethnicity on menopausal symptoms. Understanding similarities and differences among women's perceptions, attitudes, and expectations surrounding menopause improves delivery of culturally appropriate care and promotes lifestyles that may decrease symptoms and increase quality of life. Historically, the majority of the research in this area has been conducted in Western countries with clinical samples of women predominantly from European backgrounds. Thus, this population has shaped the emerging clinical picture of the midlife menopausal transition. Recently, studies of non-European women, both in the United States and internationally, indicate significant variations in their experiences during this transition, but these cultural differences have not broadened the understanding of the meaning of this universal experience. To date, there are still large knowledge gaps in race, ethnic, and cultural differences in menopausal health. The content of this review summarizes the current body of knowledge on racial differences in the menopause experience.
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PURPOSE - Effective and organ specific doses of ionizing radiation during videourodynamics are unknown. We estimated radiation exposure in children undergoing videourodynamics, and identified patient and examination factors that contribute to higher dosing.
MATERIALS AND METHODS - Fluoroscopy data were collected from consecutive patients undergoing videourodynamics. Documented dose metrics were used to calculate entrance skin dose after applying a series of correction factors. Effective doses and organ specific doses (ovaries/testes) were estimated from entrance skin dose using Monte Carlo methods on a mathematical anthropomorphic phantom (ages 0, 1, 5, 10 and 15 years). Regression analysis was performed to determine patient and procedural factors associated with higher dosing.
RESULTS - A total of 100 children (45% male, mean ± SD age 9.3 ± 5.7 years) were studied. Diagnoses included neurogenic bladder (73%), anatomical abnormality (14%) and functional/nonneurogenic disorder (13%). Mean fluoroscopy time was 0.17 ± 0.12 minutes. Mean age adjusted entrance skin dose, effective dose, and testis and ovary doses were 2.18 ± 2.00 mGy, 0.07 ± 0.05 mSv, 0.09 ± 0.10 mGy and 0.20 ± 0.13 mGy, respectively. On univariate analysis age, height, weight, body mass index, bladder capacity and fluoroscopy time were associated with effective dose. On multivariate adjusted analysis, body mass index, bladder capacity and fluoroscopy time were independently associated with effective dose.
CONCLUSIONS - The average effective dose of ionizing radiation from videourodynamics was less compared to voiding cystourethrogram dose reported in the literature. Greater fluoroscopy time, body mass index and bladder capacity are independently associated with higher dosing.
Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
OBJECTIVE - The timing of menopause is associated with multiple chronic diseases. Tools that predict this milestone have relevance for clinical and research purposes. Among infertile women, a positive relationship exists between antral follicle count (AFC) and response to controlled ovarian hyperstimulation, a marker of ovarian reserve. However, an age-independent relationship between AFC and menopause has not been demonstrated. Thus, our objective was to evaluate the relationship between AFC measured in women aged 34 to 49 years and incident natural menopause during 7 years of follow-up.
METHODS - The Coronary Artery Risk Development in Young Adults Study is a longitudinal community-based study (Chicago, IL; Birmingham, AL; Minneapolis, MN; and Oakland, CA) begun in 1985-1986. In 2002-2003, the Coronary Artery Risk Development in Young Adults Women's Study measured follicle-stimulating hormone (FSH) levels and performed a transvaginal ultrasound protocol that included AFC (2-10 mm follicles on both ovaries). Incident natural menopause was assessed by surveys in 2005-2006 and 2009-2010.
RESULTS - In our sample (n = 456), the median (interquartile range) AFC and FSH level were 5 (2-9) and 7.8 (5.6-11.0) mIU/mL, respectively, at a mean (range) age of 42 (34-49) years in 2002-2003. One hundred one women reported natural menopause by 2009-2010. In Cox models, current smoking, stable menses, FSH level higher than 13 mIU/mL, and AFC of 4 or less were independently associated with incident natural menopause. Compared with AFC higher than 4, those with an AFC of 4 or less were nearly twice as likely to have undergone menopause during 7 years of follow-up (hazard ratio, 1.89; 95% CI, 1.19-3.02) after adjustment for covariates.
CONCLUSIONS - AFC has been found to be independently associated with natural menopause during 7 years of follow-up after controlling for other markers of ovarian aging.
Preconception counseling provides an opportunity for health care providers to promote maternal and neonatal health, and to make recommendations regarding the optimization of natural fertility. While educating patients on the negative impact of maternal obesity on fertility and maternal and neonatal health; many health care providers recommend weight loss to reduce these negative outcomes. The recommendations start with lifestyle modifications, including diet and exercise. This article focuses on the available evidence regarding lifestyle modifications and fertility, and on the type of lifestyle modifications that health care providers should recommend to patients seeking to optimize their natural fertility.
Copyright © 2012. Published by Elsevier Inc.
Involvement of the ovary and/or fallopian tube by an endometrial cancer is uncommon but clinically significant because this is one of the indications for adjuvant chemotherapy. The authors evaluated whether the routine microscopic evaluation of the adnexal organs in this setting should be of the entire specimen or of representative sections. Slides and reports were reviewed for 105 consecutive patients who underwent a staging salpingo-oophorectomy (205 ovaries, 210 tubes) for endometrial carcinoma/carcinosarcoma. The study period encompassed the periods before and after an institutional policy change from discretionary (predominantly representative) adnexal sampling to obligatory total processing. Ninety-four and 111 ovaries (and 92 and 118 tubes) were entirely and representatively processed, respectively. Even when using the most expansive definition of ovarian gross abnormality (definition with the highest sensitivity and lowest specificity for microscopically confirmed cancer), we still identified 4 (of 148; 2.7%) grossly normal ovaries and 3 (of 187; 1.6%) grossly normal tubes that were found to harbor microscopic cancers. There was no significant increase in the number of grossly occult cancers detected after the policy change, and 5 (71%) of the 7 grossly occult cancers were in the representatively sampled group. Approximately 3.76 more blocks per patient were required for total overrepresentative processing, and the total cost of these additional sections was estimated to be $25.57 per patient. In conclusion, the 1.6% to 2.7% of grossly normal adnexa that proved to be cancerous represents, at least theoretically, the risk for misdiagnosis and understaging that is associated with representative sampling, at relatively modest savings. However, the findings in this study do not provide direct evidentiary support for routine complete processing.
Copyright © 2013 Elsevier Inc. All rights reserved.
PURPOSE - We aimed to assess the late effects of ovarian salvage or oophorectomy on gonadal function and fertility as measured by menstrual regularity.
METHODS - We performed a 10-year retrospective review of females aged 20 years or younger who required surgery to treat an ovarian disorder. A mail survey was distributed to these patients to evaluate the effects of ovarian surgery on menarche, menstrual regularity, and pregnancy.
RESULTS - A total of 180 females had surgery to treat an ovarian disorder. Eighty-six of these underwent unilateral oophorectomy (48%), whereas 94 (52%) had an ovary sparing procedure. Eighty-one patients (45%) returned completed surveys. Of the respondents, 44 had oophorectomy, and 37 had ovarian salvage. Ages of menarche were similar between surgical groups. Symptoms of menstrual irregularity differed most significantly according to painful menses (oophorectomy, 27.3%; salvage, 59.5%; P < .04). Interestingly, continuation of regular menses after surgery was higher in the oophorectomy group (oophorectomy, 70%; salvage, 15%; P = .013).
CONCLUSIONS - Unilateral oophorectomy does not appear to impair late gonadal function when compared with ovarian salvage. Surprisingly, oophorectomy appears to maintain more normal ovarian activity as estimated by menstrual regularity. Oophorectomy may be performed without apparent adverse effect on gonadal activity.
Copyright © 2012 Elsevier Inc. All rights reserved.