Prenatal exposure to high galactose adversely affects initial gonadal pool of germ cells in rats

Prenatal exposure to high galactose adversely affects initial gonadal pool of germ cells in rats
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DOI:
10.1093/humrep/deg058
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发表时间:
2003-02-01
期刊:
影响因子:
6.1
通讯作者:
Kabir, SN
Kabir, SN
中科院分区:
医学1区
文献类型:
--
作者:
Bandyopadhyay, S;Chakrabarti, J;Kabir, SN

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背景:在大鼠中,产前暴露于高浓度半乳糖可能导致一种相当于人类半乳糖血症的卵巢早衰(POF)成分的疾病。我们研究了实验性半乳糖样贫血条件下POF的发展是否归因于生殖细胞迁移受损。方法:从怀孕第3天开始,给怀孕大鼠喂食添加或不添加35%半乳糖的微丸,一直持续到分娩。在12-15天之间,从一个子宫角中取出胚胎。原始生殖细胞(PGC)的组织化学定位和计数是基于Dolichos biflorus凝集素(一种末端n -乙酰半乳糖胺(GaINAc)特异性凝集素)与生殖细胞表面糖缀合物的结合。从另一个子宫角取出的胚胎一直保存到分娩。在1-2日龄雌性幼犬的肝脏中,检测了参与GaINAc合成过程多个步骤的尿苷二磷酸半乳糖4- epimase的肝脏活性。结果:半乳糖暴露组各检测日特异性部位PGC数量显著降低(P <或等于0.0003),肝脏epimase活性显著降低(P = 0.000001)。结论:生殖细胞迁移障碍导致性腺发育缺乏初始生殖细胞池可能是半乳糖血症与POF之间的因果关系。
BACKGROUND: In rats, prenatal exposure to high concentrations of galactose may contribute to a condition that is equivalent to the premature ovarian failure (POF) component of human galactosaemia. We investigated if development of POF under experimental galactosaemia-like conditions was attributed to impaired germ cell migration. METHODS: Pregnant rats were fed pellets supplemented with, or without, 35% galactose from day 3 of conception continuing through parturition. Between days 12-15, embryos from one uterine horn were dissected out. Primordial germ cells (PGC) were histochemically localized and counted on the basis of binding of Dolichos biflorus agglutinin, a lectin specific for terminal N-acetylgalactosamine (GaINAc), to the surface glycoconjugate of the germ cells. The embryos from the other uterine horn were maintained until parturition. Liver activity of uridine diphosphate galactose 4-epimerase, the enzyme involved at multiple steps in the process of synthesis of GaINAc, was assayed in 1-2 day old female pups. RESULTS: The numbers of PGC at the day-specific sites on all days of examination were significantly lower (P less than or equal to 0.0003), and liver epimerase activity was significantly (P = 0.000001) reduced in the galactose-exposed group. CONCLUSION: Impaired germ cell migration leading to the development of gonads with deficient initial pools of germ cells may form the causal link between galactosaemia and POF.