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的变化，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通过控制胎盘中氨基酸的运输来增加胎儿体重。视黄醇、胰岛素和胰岛素样生长因子也增加了氨基酸的转运。表皮生长因子可促进新生大鼠肠道功能和形态的发育，这种作用可被鸟氨酸脱羧酶的不可逆抑制剂DL-α-二氟甲基鸟氨酸抑制，抑制多胺的合成也可引起宫内生长受限。胎盘组织中ODC活性的抑制是DEMO致IUGR的主要因素，多形核激素在妊娠过程中起着重要作用。妊娠晚期胎盘中非特异性δ-氨基酮戊酸合成酶和血红素加氧酶-1的转录水平显著升高，且这些酶仅在滋养层细胞中表达。这两种酶都受到急性胎儿缺氧的影响，提示胎盘的血红素代谢受到氧气供应的影响。我们建立了西瑞普佐菌素(STZ)治疗的妊娠大鼠糖尿病和类似先兆子痫的体征和症状的模型。该模型可用于糖尿病妊娠病理生理学的基础研究。这些数据表明，许多激素、生长因子和与细胞生长有关的物质如EGF、多胺、胰岛素、维甲酸在围产期起着重要的作用。

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.