Research for the perinatal adaptation of fetus and newborn ; relation to apoptosis and growth factor

胎儿和新生儿表现出许多生理和代谢变化，以适应分娩周围剧烈的环境变化。我们研究了与这些变化相关的激素、生长因子和物质。EGF通过控制氨基酸在胎盘中的转运而增加胎儿体重。视黄醇、胰岛素和胰岛素样生长因子也增加了氨基酸运输。EGF促进新生大鼠肠道功能和形态发育，这种变化被不可逆的鸟氨酸脱羧酶（ODC）抑制剂DL-α-二氟甲基鸟氨酸（DFMO）抑制。DFMO对多胺合成的抑制也会导致宫内生长受限。胎盘中ODC活性的降低是DEMO诱导IUGR的主要因素，多嘌呤在妊娠中起重要作用。我们研究了胎盘中的血红素代谢。妊娠末期胎盘中非特异性δ-氨基乙酰酸合成酶和血红素加氧酶-1的转录水平显著升高，且这些酶仅在滋养细胞中表达。这两种酶均受胎儿急性缺氧的影响，提示胎盘血红素代谢受氧供应的影响。我们建立了sireptozocin （STZ）治疗的糖尿病妊娠大鼠模型，并模拟子痫前期的体征和症状。该模型对妊娠合并糖尿病的病理生理基础研究具有重要意义。这些数据表明，许多与细胞生长有关的激素、生长因子和物质，如EGF、多胺、胰岛素、类维生素a等，在围产期起着重要作用。

Fetus and newborn show the many physiological and metabolic changes to adapt the dramatic environmental changes around the delivery. We investigated the hormones, growth factors and substances related to these changes.EGF increased fetal weight by controlling the amino acid transport in placenta. Retinol, insulin and insulin like growth factor also increased amino acid transport. EGF promoted the functional and morphological development of neonatal rat intestine and this change was inhibited by DL-α-difluoromethyl ornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC).Inhibition of polyamine synthesis by DFMO also induced intrauterine growth restriction. The depression of ODC activity in the placenta is the major factor of IUGR induced by DEMO administration, and polyatnines play important roles to carry pregnancy.We investigated heme metabolism in placenta. Transcription levels of the non-specific δ-aminolevulinate synthase and heme oxygenase-1 in placenta at the terminal stage of pregnancy were increased markedly and these enzymes were exclusively expressed in the trophoblast. Both enzymes were influenced by acute fetal hypoxia and suggest that placental heme metabolism is influenced by the oxygen supply.We established a sireptozotocin (STZ)-treated pregnant rat model with diabetes and signs and symptoms mimicking preeclampsia. This model closely is useful for basic study of the pathophysiology of pregnancy with diabetes.These data suggest that many hormones, growth factors and substances such as EGF, polyamine, insulin, retinoids which related to cell growth play some important roll during the perinatal period.