المؤلفون: Danica Ryan, Victor G. Puelles, Alison L. Kent, John F. Bertram, Melissa H. Little, Lynette Moore, Andrew P. McMahon, Megan R. Sutherland, Jane E. Dahlstrom, Mary Jane Black, Tracey J. Flores

المصدر: EBioMedicine, Vol 27, Iss C, Pp 275-283 (2018)
EBioMedicine
EBioMedicine 27, 275-283 (2018). doi:10.1016/j.ebiom.2017.12.016

مصطلحات موضوعية: 0301 basic medicine, Male, Time Factors, Kidney development, Organogenesis, Kidney Glomerulus, 030232 urology & nephrology, Physiology, Podocyte, lcsh:Medicine, Nephrogenesis, Biology, Kidney, Weight Gain, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Fetus, Pregnancy, medicine, Humans, lcsh:R5-920, urogenital system, lcsh:R, Gestational age, Infant, General Medicine, Organ Size, Renal corpuscle, 030104 developmental biology, medicine.anatomical_structure, In utero, Glomerulus, Term Birth, Gestation, Female, lcsh:Medicine (General), Research Paper

الوصف: Background During normal human kidney development, nephrogenesis (the formation of nephrons) is complete by term birth, with the majority of nephrons formed late in gestation. The aim of this study was to morphologically examine nephrogenesis in fetal human kidneys from 20 to 41 weeks of gestation. Methods Kidney samples were obtained at autopsy from 71 infants that died acutely in utero or within 24 h after birth. Using image analysis, nephrogenic zone width, the number of glomerular generations, renal corpuscle cross-sectional area and the cellular composition of glomeruli were examined. Kidneys from female and male infants were analysed separately. Findings The number of glomerular generations formed within the fetal kidneys was directly proportional to gestational age, body weight and kidney weight, with variability between individuals in the ultimate number of generations (8 to 12) and in the timing of the cessation of nephrogenesis (still ongoing at 37 weeks gestation in one infant). There was a slight but significant (r2 = 0.30, P = 0.001) increase in renal corpuscle cross-sectional area from mid gestation to term in females, but this was not evident in males. The proportions of podocytes, endothelial and non-epithelial cells within mature glomeruli were stable throughout gestation. Interpretation These findings highlight spatial and temporal variability in nephrogenesis in the developing human kidney, whereas the relative cellular composition of glomeruli does not appear to be influenced by gestational age.
Highlights • There is spatial and temporal variability in nephrogenesis in the developing human kidney. • The relative cellular composition of mature glomeruli does not appear to be influenced by gestational age. • There is apparent sexual dimorphism in the growth of glomeruli during late gestation. The number of glomeruli (filtering units of the kidneys) you are born with directly influences your life-long kidney health, therefore it is important to understand how they are formed. Between mid-pregnancy and term, there was variability between individuals in relation to the number of layers of glomeruli formed in the developing kidney, and variation in the timing of when they stopped being formed. In fully-formed glomeruli, the proportion of the different cell types in glomeruli remained constant within the developing kidneys throughout pregnancy. Female infants, but not males, exhibited an increase in the size of glomeruli from mid-pregnancy to term.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::825dc573140439872266f35cc581a07dTest
http://www.sciencedirect.com/science/article/pii/S2352396417304954Test

المؤلفون: Megan R. Sutherland, Mary Jane Black, Danica Vojisavljevic

المصدر: Anatomical record (Hoboken, N.J. : 2007)REFERENCES. 303(10)

مصطلحات موضوعية: 0301 basic medicine, Developmental stage, Histology, Cellular composition, urogenital system, Kidney Glomerulus, Stereology, Nephrons, Biology, urologic and male genital diseases, Kidney, Glomerular capillary, Podocyte, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, medicine, Animals, Humans, Anatomy, 030217 neurology & neurosurgery, Ecology, Evolution, Behavior and Systematics, Biotechnology, Biomedical engineering

الوصف: The evaluation of a range of measures in the kidneys, such as developmental stage, rate and success, injury, and disease processes, relies on obtaining information on the three-dimensional structure of the renal corpuscles, and in particular the glomerular capillary tufts. To do this in the most accurate, comprehensive, and unbiased manner depends on a knowledge of stereological methods. In this article, we provide a practical guide for researchers on how to quantitate a number of structures in the kidneys, including the estimation of total glomerular number, glomerular capillary length and filtration surface area, and the cellular composition of individual glomeruli. Guidance is also provided on how to apply these methods to kidneys at different sizes and levels of maturity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eaaa9c571614d4e34b4b66a8907505dcTest
https://pubmed.ncbi.nlm.nih.gov/31960613Test

المؤلفون: Lina Gubhaju, John F. Bertram, M. Jane Black, Lynette Moore, Wendy E. Hoy, Alison L. Kent, Rosemary S.C. Horne, Megan R. Sutherland, Jane E. Dahlstrom

المصدر: Journal of the American Society of Nephrology. 22:1365-1374

مصطلحات موضوعية: Male, Nephrology, medicine.medical_specialty, Urinary system, Kidney Glomerulus, Physiology, Gestational Age, Nephron, urologic and male genital diseases, Clinical Research, Cause of Death, Internal medicine, medicine, Humans, Pregnancy, Kidney, urogenital system, business.industry, Infant, Newborn, Gestational age, General Medicine, medicine.disease, Renal corpuscle, Low birth weight, Endocrinology, medicine.anatomical_structure, Premature Birth, medicine.symptom, business, Infant, Premature

الوصف: Nephrogenesis is ongoing at the time of birth for the majority of preterm infants, but whether postnatal renal development follows a similar trajectory to normal in utero growth is unknown. Here, we examined tissue collected at autopsy from 28 kidneys from preterm neonates, whose postnatal survival ranged from 2 to 68 days, including 6 that had restricted intrauterine growth. In addition, we examined kidneys from 32 still-born gestational controls. We assessed the width of the nephrogenic zone, number of glomerular generations, cross-sectional area of the renal corpuscle, and glomerular maturity and morphology. Renal maturation accelerated after preterm birth, with an increased number of glomerular generations and a decreased width of the nephrogenic zone in the kidneys of preterm neonates. Of particular concern, compared with gestational controls, preterm kidneys had a greater percentage of morphologically abnormal glomeruli and a significantly larger cross-sectional area of the renal corpuscle, suggestive of renal hyperfiltration. These observations suggest that the preterm kidney may have fewer functional nephrons, thereby increasing vulnerability to impaired renal function in both the early postnatal period and later in life.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6e67ea8ececadc47a586f3991720dc27Test
https://doi.org/10.1681/asn.2010121266Test

المؤلفون: M. Jane Black, Bradley A. Yoder, Megan R. Sutherland, Lina Gubhaju, Mildred T. Stahlman

المصدر: Pediatric Research. 65:397-402

مصطلحات موضوعية: Vascular Endothelial Growth Factor A, medicine.medical_specialty, Organogenesis, Urinary system, Kidney Glomerulus, Retinoic acid, Kidney development, Gestational Age, Tretinoin, Kidney Volume, Nephron, Kidney, urologic and male genital diseases, Article, chemistry.chemical_compound, Pregnancy, biology.animal, Internal medicine, medicine, Animals, Birth Weight, WT1 Proteins, In Situ Hybridization, biology, Podocytes, urogenital system, Nephrons, Organ Size, Vitamins, Immunohistochemistry, Renal corpuscle, Platelet Endothelial Cell Adhesion Molecule-1, medicine.anatomical_structure, Endocrinology, Animals, Newborn, chemistry, Pediatrics, Perinatology and Child Health, Premature Birth, Female, Papio, Baboon

الوصف: Administration of retinoic acid, the active metabolite of vitamin A, is linked to the stimulation of nephrogenesis. The aim of this study was to determine whether early postnatal administration of retinoic acid (RA) could enhance ongoing nephrogenesis in a baboon model of premature birth. Unbiased stereological methods were employed to estimate kidney volume, renal corpuscle volume and nephron number. The percentage of abnormal glomeruli and the number of glomerular generations were also determined in the kidneys of preterm control (n=6) and preterm +RA (n=6) animals that received 500 μg/kg/day of all-trans retinoic acid following premature delivery. There was no significant difference between the preterm control and the preterm +RA groups in kidney size, nephron number (preterm control: 329,924 ± 41,752; preterm +RA: 354,041 ± 52,095; p = 0.59), renal corpuscle volume, number of glomerular generations, or the percentage of abnormal glomeruli. The proportion of abnormal glomeruli did not appear to be linked to any elements of postnatal care examined. The results of this study indicate that early postnatal administration of retinoic acid is unable to stimulate nephrogenesis in the kidney of the preterm baboon. Encouragingly, it does not appear to have any adverse effects on kidney development.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::751568213207cee3136f8b46850ca1afTest
https://doi.org/10.1203/pdr.0b013e3181975f52Test

المؤلفون: Lynette Moore, Megan R. Sutherland, Jane E. Dahlstrom, Lina Gubhaju, Mary Jane Black, Alison L. Kent

المصدر: Nephrology. 18:180-182

مصطلحات موضوعية: medicine.medical_specialty, Kidney, Renal circulation, urogenital system, business.industry, Renal cortex, Kidney development, General Medicine, Nephron, urologic and male genital diseases, medicine.anatomical_structure, Endocrinology, Blood pressure, Nephrology, Internal medicine, Renal blood flow, medicine, Gestation, business

الوصف: Preterm birth (birth prior to 37 completed weeks of gestation) may occur at a time when the infant kidney is very immature and nephrogenesis is often ongoing. In autopsied preterm human kidneys and in a baboon model of preterm birth it has been shown that nephrogenesis continues after preterm birth, with a significant increase in the number of glomerular generations and number of nephrons formed within the kidney after birth. Of concern, however, morphologically abnormal glomeruli (with a cystic Bowman's space) are often observed; the abnormal glomeruli are only located in the outer renal cortex, suggesting that it is the recently formed glomeruli (perhaps those formed in the extra-uterine environment) that are affected. The proportion of abnormal glomeruli within the renal cortex differs between infants with some kidneys appearing normal whereas others are severely affected. This suggests that it may be haemodynamic factors and/or factors in the neonatal care of the infant that lead to the glomerular abnormalities. Indeed, the haemodynamic transition at birth where there is a marked increase in systemic blood pressure and renal blood flow are likely to lead to injury of glomerular capillaries, although further studies are required to elucidate this. In order to optimize renal health at the beginning of life in the preterm infant, it is imperative in future studies to gain an understanding of the causes of the glomerular abnormalities in the preterm neonate.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::8e5cf3829c97b517b4cd16b12ba32b50Test
https://doi.org/10.1111/nep.12028Test

المؤلفون: John F. Bertram, Bradley A. Yoder, Anthony Zulli, Megan R. Sutherland, M. Jane Black, Lina Gubhaju

المصدر: Monash University

مصطلحات موضوعية: Vascular Endothelial Growth Factor A, medicine.medical_specialty, Physiology, Urinary system, Kidney Glomerulus, Stereology, Biology, Kidney, urologic and male genital diseases, Pregnancy, Internal medicine, biology.animal, medicine, Animals, Tissue Distribution, RNA, Messenger, WT1 Proteins, Glucocorticoids, Podocytes, urogenital system, Body Weight, Kidney metabolism, Organ Size, Articles, medicine.disease, Immunohistochemistry, Platelet Endothelial Cell Adhesion Molecule-1, Endocrinology, medicine.anatomical_structure, Animals, Newborn, Premature birth, Prenatal Exposure Delayed Effects, Premature Birth, Gestation, Female, Biomarkers, Papio, Baboon

الوصف: Nephrogenesis occurs predominantly in late gestation at a time when preterm infants are already delivered. The aims of this study were to assess the effect of preterm birth and the effect of antenatal glucocorticoid treatment on nephrogenesis. Preterm baboons, which were delivered at 125 days gestation and ventilated for up to 21 days postnatally, were compared with gestational controls. A cohort of preterm baboons that had been exposed to antenatal glucocorticoids were compared with unexposed preterm baboons. The number of glomerular generations was estimated using a medullary ray glomerular-counting method, and glomerular number was estimated using unbiased stereology. CD31 and WT-1 localization was examined using immunohistochemistry and VEGF was localized using in situ hybridization. The number of glomerular generations was not affected by preterm birth, and total glomerular numbers were within the normal range. Kidneys were significantly enlarged in preterm baboons with a significant decrease in glomerular density (number of glomeruli per gram of kidney) in the preterm kidney compared with gestational controls. Neonates exposed to antenatal steroids had an increased kidney-to-body weight ratio and also more developed glomeruli compared with unexposed controls. Abnormal glomeruli, with a cystic Bowman's space and shrunken glomerular tuft, were often present in the superficial renal cortex of both the steroid-exposed and unexposed preterm kidneys; steroid exposure had no significant effect on the proportion of abnormal glomeruli. The proportion of abnormal glomeruli in the preterm kidneys ranged from 0.2 to 18%. In conclusion, although nephrogenesis is ongoing in the extrauterine environment, our findings demonstrate that preterm birth, independent of steroid exposure, is associated with a high proportion of abnormal glomeruli in some, but not all neonatal kidneys. Whether final nephron endowment is affected in those kidneys exhibiting a high proportion of abnormal glomeruli is yet to be confirmed.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9f3f1459f769873b9dcd1e45f466f22eTest
https://research.monash.edu/en/publications/3b9a299e-121f-4f5d-8adb-68e590171111Test