Iwasa Takeshi, Matsuzaki Toshiya, Murakami Masahiro, Kinouchi Riyo, Gereltsetseg Ganbat, Yamamoto Satoshi, Kuwahara Akira, Yasui Toshiyuki, Irahara Minoru
Department of Obstetrics and Gynecology, The University of Tokushima Graduate School, Institute of Health Biosciences, 3-18-15 Kuramoto-Cho, Tokushima 770-8503, Japan.
Int J Dev Neurosci. 2011 Apr;29(2):183-8. doi: 10.1016/j.ijdevneu.2010.11.001. Epub 2010 Nov 11.
Intrauterine growth retardation (IUGR) is an important risk factor for the pathogenesis of diseases after birth. Long-lasting alterations in the structure and function of tissues and the neuroendocrine system, which are known as 'programming effects', increase the risks of these diseases. To investigate the pathophysiology of programming effects, several kinds of IUGR rodent models have been used in experiments. Sexual maturation and the onset of puberty are delayed in these models. We have previously reported that decreased action of hypothalamic kisspeptin, which is a positive regulator of GnRH, contributes to the delayed onset of puberty in undernutrition-induced IUGR rats. The aim of this study was to evaluate whether the hypothalamic Kiss1-Kiss1r-GnRH system is also altered in dexamethasone-induced IUGR rats. Compared with offspring from an untreated mother (control), offspring from a dexamethasone administered mother (DEX) showed a significant reduction in body weight throughout the experimental period (from birth to the prepubertal period) and the delayed onset of puberty. There were no significant differences between the control and DEX groups with regard to their hypothalamic Kiss1, Kiss1r, GnRH, CRH, NPY and POMC mRNA levels during the experimental period or their serum LH, FSH, or leptin concentrations at postnatal day 28 or vaginal opening (VO). Compared with the control, DEX showed significantly lower ovarian weight at postnatal day 28, but not at VO. These results suggested that the delayed onset of puberty induced by maternal dexamethasone administration would occur independently of hypothalamic Kiss1-Kiss1r-GnRH system.
宫内生长受限（IUGR）是出生后疾病发病机制的一个重要风险因素。组织和神经内分泌系统结构与功能的长期改变，即所谓的“编程效应”，会增加这些疾病的风险。为了研究编程效应的病理生理学，实验中使用了几种IUGR啮齿动物模型。在这些模型中，性成熟和青春期的开始会延迟。我们之前报道过，下丘脑促性腺激素释放激素（GnRH）的正向调节因子 kisspeptin 的作用降低，导致营养不良诱导的 IUGR 大鼠青春期开始延迟。本研究的目的是评估下丘脑 Kiss1-Kiss1r-GnRH 系统在 dexamethasone 诱导的 IUGR 大鼠中是否也发生改变。与未处理母亲的后代（对照组）相比，dexamethasone 处理母亲的后代（DEX 组）在整个实验期（从出生到青春期前期）体重显著降低，青春期开始延迟。在实验期内，对照组和 DEX 组在下丘脑 Kiss1、Kiss1r、GnRH、促肾上腺皮质激素释放激素（CRH）、神经肽 Y（NPY）和阿黑皮素原（POMC）mRNA 水平方面，以及在出生后第 28 天或阴道开口（VO）时的血清促黄体生成素（LH）、促卵泡生成素（FSH）或瘦素浓度方面，均无显著差异。与对照组相比，DEX 组在出生后第 28 天卵巢重量显著降低，但在 VO 时无差异。这些结果表明，母体给予 dexamethasone 诱导的青春期开始延迟与下丘脑 Kiss1-Kiss1r-GnRH 系统无关。
