Department of Obstetrics and Gynecology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima 770-8503, Japan.
J Physiol. 2010 Mar 1;588(Pt 5):821-9. doi: 10.1113/jphysiol.2009.183558. Epub 2010 Jan 18.
Recent studies have suggested that intrauterine undernutrition is closely associated with the pathogenesis of diseases after birth. Perinatal undernutrition is known to disturb the development of reproductive function and delay the onset of puberty in some species. Using a rat model, we determined the effects of prenatal undernutrition on the development of the hypothalamic kisspeptin system and evaluated whether the alteration of the kisspeptin system contributes to the delayed onset of puberty induced by prenatal undernutrition. We also evaluated the effects of prenatal undernutrition on the developmental changes in serum leptin levels because leptin was a putative positive regulator of the hypothalamic kisspeptin system. We compared the timing of vaginal opening (VO) and the developmental changes in body weight, hypothalamic Kiss1 mRNA levels, and serum leptin concentrations between offspring with prenatal undernutrition (UN offspring) and normal nutrition (NN offspring). After birth, the UN offspring showed rapid growth and had caught up to body weight of the NN offspring by postnatal day 12. After postnatal day 16, the UN offspring showed significantly lower Kiss1 mRNA levels than the NN offspring, despite their significantly higher serum leptin levels (at days 20 and 28). The timing of VO in the UN offspring was delayed compared with that in the NN offspring, and chronic central injection of kisspeptin normalized the timing of VO in the UN offspring. These results suggest that decreased hypothalamic kisspeptin action contributes to the delayed onset of puberty in prenatally undernourished female rats. Increased leptin resistance in the kisspeptin system might be involved in these alterations.
最近的研究表明，宫内营养不良与出生后疾病的发病机制密切相关。围产期营养不良已知会干扰某些物种生殖功能的发育，并延迟青春期的开始。使用大鼠模型，我们确定了产前营养不良对下丘脑 kisspeptin 系统发育的影响，并评估了 kisspeptin 系统的改变是否导致产前营养不良引起的青春期延迟。我们还评估了产前营养不良对血清瘦素水平发育变化的影响，因为瘦素是下丘脑 kisspeptin 系统的一个假定正调节剂。我们比较了有产前营养不良（UN 后代）和正常营养（NN 后代）的后代的阴道开口（VO）时间和体重、下丘脑 Kiss1 mRNA 水平和血清瘦素浓度的发育变化。出生后，UN 后代生长迅速，到出生后第 12 天体重赶上 NN 后代。出生后第 16 天，尽管 UN 后代的血清瘦素水平显著升高（第 20 天和第 28 天），但其 Kiss1 mRNA 水平明显低于 NN 后代。UN 后代的 VO 时间延迟，而慢性中枢注射 kisspeptin 使 UN 后代的 VO 时间正常化。这些结果表明，下丘脑 kisspeptin 作用的降低导致了产前营养不良雌性大鼠青春期的延迟。kisspeptin 系统中瘦素抵抗的增加可能涉及这些改变。
