Engelbregt Mia J T, van Weissenbruch Mirjam M, Lips Paul, van Lingen Arthur, Roos Jan C, Delemarre-van de Waal Henriette A
Department of Clinical Chemistry, The Research Institute for Endocrinology, Reproduction and Metabolism, VU University Medical Center, 1007 MB Amsterdam, The Netherlands.
Bone. 2004 Jan;34(1):180-6. doi: 10.1016/j.bone.2003.04.001.
Undernutrition in early life may permanently change body structure, physiology and metabolism and leads to chronic diseases in later life. To test whether malnutrition during different critical time periods around birth in the rat has long-lasting effects on body composition and skeletal growth, we examined body weight and body composition in pubertal rats and adult rats of 6 months after pre- and postnatal malnutrition. Prenatal malnutrition or intra-uterine growth retardation (IUGR) was induced by ligation of the uterine arteries on day 17 of gestation and postnatal food restriction (FR) by litter enlargement to 20 pups per mother from day 2 after birth until weaning (day 24). Pubertal markers were balanopreputial separation (BPS) in the male and vaginal opening (VO) in the female. IUGR as well as FR resulted in a persistent growth retardation. From birth in IUGR rats and from day 4 after birth in FR rats until 6 months of age body weight in male and female rats was significantly lower compared with controls (P < 0.01 and P < 0.05). Although total body bone mineral content (TBBMC) did not differ between male IUGR rats and controls at BPS, at the age of 6 months TBBMC was significantly lower (P < 0.01) compared with controls. At BPS as well as at 6 months of age, TBBMC was significantly lower in male FR rats compared with controls (P < 0.05 and P < 0.01). In the female IUGR rats TBBMC was significantly lower compared with controls at VO (P < 0.01) and 6 months (P < 0.05). TBBMC in the female FR rats was significantly lower at VO (P < 0.01), but did not differ from controls at the age of 6 months. For both IUGR and FR male and female rats these differences disappeared after adjusting for body weight. Body composition in terms of total fat mass, percentage fat and percentage lean did not differ from controls in male and female IUGR rats at 6 months and the same results were observed in the female FR rats. However, in the male FR rats, total fat mass and percentage fat were significantly lower compared with controls (P < 0.01 and P < 0.05), while the percentage lean mass was significantly higher (P < 0.05). We conclude that different critical time periods of malnutrition around birth have different effects later in life on growth, which do not disappear at least after 6 months of life. With respect to body composition, only in the FR male rats, differences are found in total fat mass and the balance of percentage fat mass and lean mass. At time of puberty and at the age of 6 months bone mass adjusted for body weight does not seem to be affected by perinatal undernutrition.
生命早期的营养不良可能会永久性地改变身体结构、生理机能和新陈代谢,并导致日后患上慢性疾病。为了测试大鼠出生前后不同关键时期的营养不良是否会对身体组成和骨骼生长产生长期影响,我们研究了产前和产后营养不良的青春期大鼠和6个月大成年大鼠的体重和身体组成。通过在妊娠第17天结扎子宫动脉诱导产前营养不良或宫内生长迟缓(IUGR),并通过从出生后第2天至断奶(第24天)将每只母鼠的窝仔数增加到20只来诱导产后食物限制(FR)。青春期指标在雄性为包皮分离(BPS),在雌性为阴道开口(VO)。IUGR以及FR均导致持续生长迟缓。从IUGR大鼠出生时起以及从FR大鼠出生后第4天起直至6个月龄,雄性和雌性大鼠的体重均显著低于对照组(P < 0.01和P < 0.05)。尽管雄性IUGR大鼠与对照组在BPS时的全身骨矿物质含量(TBBMC)没有差异,但在6个月龄时,TBBMC显著低于对照组(P < 0.01)。在BPS以及6个月龄时,雄性FR大鼠的TBBMC显著低于对照组(P < 0.05和P < 0.01)。在雌性IUGR大鼠中,VO时(P < 0.01)和6个月时(P < 0.05)的TBBMC显著低于对照组。雌性FR大鼠VO时的TBBMC显著降低(P < 0.