Altered ureteric branching morphogenesis and nephron endowment in offspring of diabetic and insulin-treated pregnancy.
Altered ureteric branching morphogenesis and nephron endowment in offspring of diabetic and insulin-treated pregnancy.
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DOI：
10.1371/journal.pone.0058243
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Cullen-McEwen LA
中科院分区：
文献类型：
--
作者：
Hokke SN;Armitage JA;Puelles VG;Short KM;Jones L;Smyth IM;Bertram JF;Cullen-McEwen LA
来自人类和动物模型的强有力证据表明，在子宫内发育期间暴露于母体高血糖症会对胎儿肾脏发育产生不良影响。尽管有这些知识，但由于缺乏研究和以前使用的方法的局限性，糖尿病妊娠对肾脏发育关键过程的确切影响尚不清楚。本研究的目的是利用无偏技术阐明高血糖对输尿管分支形态发生和肾发生的影响。在胚胎日（E）6.5-8.5使用多剂量的链脲佐菌素（STZ）在妊娠C57 B1/6 J小鼠中诱导糖尿病。使用光学投影断层扫描法离体定量分支形态发生，并使用无偏体视学对肾单位进行计数。从E12.5开始识别母体高血糖症。在E14.5时，糖尿病小鼠的后代表现出胎儿生长受限，并且与对照相比，输尿管尖端数量（对照283.7±23.3 vs. STZ 153.2±24.6，平均值±SEM，p<0.01）和输尿管树长度（对照33.1±2.6 mm vs. STZ 17.6±2.7 mm，p = 0.001）明显不足。 在E18.5时，STZ母鼠的后代中仍然存在胎儿生长受限，并且观察到肾单位禀赋缺陷（对照组1246.2±64.9 vs. STZ 822.4±74.0，p<0.001）。与对照组（0%）相比，糖尿病妊娠胚胎中常见双输尿管和输尿管积水形式的肾脏畸形（26%）。从E13.5开始的母体胰岛素治疗使母体贫血正常化，但不能使胎儿体重正常化，也不能防止肾单位缺陷。高血糖对输尿管分支形态发生的不利影响，进而对生长受限胎儿的肾单位禀赋的不利影响，突出了妊娠早期和肾脏发育初始阶段血糖控制的重要性。
There is strong evidence from human and animal models that exposure to maternal hyperglycemia during in utero development can detrimentally affect fetal kidney development. Notwithstanding this knowledge, the precise effects of diabetic pregnancy on the key processes of kidney development are unclear due to a paucity of studies and limitations in previously used methodologies. The purpose of the present study was to elucidate the effects of hyperglycemia on ureteric branching morphogenesis and nephrogenesis using unbiased techniques. Diabetes was induced in pregnant C57Bl/6J mice using multiple doses of streptozotocin (STZ) on embryonic days (E) 6.5-8.5. Branching morphogenesis was quantified ex vivo using Optical Projection Tomography, and nephrons were counted using unbiased stereology. Maternal hyperglycemia was recognised from E12.5. At E14.5, offspring of diabetic mice demonstrated fetal growth restriction and a marked deficit in ureteric tip number (control 283.7±23.3 vs. STZ 153.2±24.6, mean±SEM, p<0.01) and ureteric tree length (control 33.1±2.6 mm vs. STZ 17.6±2.7 mm, p = 0.001) vs. controls. At E18.5, fetal growth restriction was still present in offspring of STZ dams and a deficit in nephron endowment was observed (control 1246.2±64.9 vs. STZ 822.4±74.0, p<0.001). Kidney malformations in the form of duplex ureter and hydroureter were a common observation (26%) in embryos of diabetic pregnancy compared with controls (0%). Maternal insulin treatment from E13.5 normalised maternal glycaemia but did not normalise fetal weight nor prevent the nephron deficit. The detrimental effect of hyperglycemia on ureteric branching morphogenesis and, in turn, nephron endowment in the growth-restricted fetus highlights the importance of glycemic control in early gestation and during the initial stages of renal development.
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影响因子：
2.5
作者：
Festing, MFW
通讯作者：
Festing, MFW
影响因子：
1.3
作者：
Ferenc Banhidy;Acs, Nandor;Czeizel, Andrew E.
通讯作者：
Czeizel, Andrew E.
影响因子：
4.2
作者：
Ballas, Jerasimos;Moore, Thomas R.;Ramos, Gladys A.
通讯作者：
Ramos, Gladys A.
DOI：
10.1111/j.1365-2613.2008.00593.x
发表时间：
2008-08-01
影响因子：
3
作者：
Cunha, Ana Rosa;Aguila, Marcia Barbosa;Mandarim-de-Lacerda, Carlos Alberto
通讯作者：
Mandarim-de-Lacerda, Carlos Alberto
DOI：
10.1002/dmr.5610060303
发表时间：
1990-12-01
期刊：
DIABETES-METABOLISM REVIEWS
影响因子：
--
作者：
AERTS, L;HOLEMANS, K;VANASSCHE, FA
通讯作者：
VANASSCHE, FA