Wallace Jacqueline M, Matsuzaki Masatoshi, Milne John, Aitken Raymond
Rowett Research Institute, Bucksburn, Aberdeen AB21 9SB, United Kingdom.
Biol Reprod. 2006 Aug;75(2):231-9. doi: 10.1095/biolreprod.106.052605. Epub 2006 May 10.
In the overnourished adolescent sheep, maternal tissue synthesis is promoted at the expense of placental growth and leads to a major decrease in lamb birth weight at term. Maternal growth hormone (GH) concentrations are attenuated in these pregnancies, and it was recently demonstrated that exogenous GH administration throughout the period of placental proliferation stimulates uteroplacental and fetal development by Day 81 of gestation. The present study aimed to determine whether these effects persist to term and to establish whether GH affects fetal growth and body composition by increasing placental size or by altering maternal metabolism. Adolescent recipient ewes were implanted with singleton embryos on Day 4 postestrus. Three groups of ewes offered a high dietary intake were injected twice daily with recombinant bovine GH from Days 35 to 65 of gestation (high intake plus early GH) or from Days 95 to 125 of gestation (high intake plus late GH) or remained untreated (high intake only). A fourth moderate-intake group acted as optimally nourished controls. Pregnancies were terminated at Day 130 of gestation (6 per group) or were allowed to progress to term (8-10 per group). GH administration elevated maternal plasma concentrations of GH, insulin, glucose, and nonesterified fatty acids during the defined treatment windows, while urea concentrations were decreased. At Day 130, GH treatment had reduced the maternal adiposity score, percentage of fat in the carcass, and internal fat depots and leptin concentrations, predominantly in the high-intake plus late GH group. Placental weight was lower in high-intake vs. control dams but independent of GH treatment. In contrast, fetal weight was elevated by late GH treatment, and these fetuses had higher relative carcass fat content, perirenal fat mass, and liver glycogen concentrations than all other groups. Expression of leptin mRNA in fetal perirenal fat and fetal plasma leptin concentrations were not significantly altered by maternal nutritional intake or GH. In pregnancies proceeding to term, the duration of gestation, fetal placental mass, and lamb birth weight were reduced in high-intake compared with control dams but were not significantly affected by GH treatment. In conclusion, exogenous GH has profound effects on maternal endocrinology, metabolism, and body composition when administered during early and late pregnancy. Treatment during late pregnancy has a modest effect on fetal growth independent of placental size and a profound effect on fetal adiposity, which may have implications beyond the fetal period.
在营养过剩的青春期绵羊中，母体组织合成增加是以胎盘生长为代价的，这会导致足月时羔羊出生体重显著下降。在这些妊娠中，母体生长激素（GH）浓度会降低，最近有研究表明，在胎盘增殖期全程给予外源性GH可在妊娠第81天时刺激子宫胎盘和胎儿发育。本研究旨在确定这些影响是否持续至足月，并确定GH是通过增加胎盘大小还是改变母体代谢来影响胎儿生长和身体组成。青春期受体母羊在发情后第4天植入单胎胚胎。三组给予高膳食摄入量的母羊在妊娠第35至65天（高摄入量加早期GH）或第95至125天（高摄入量加晚期GH）每天注射两次重组牛GH，或不进行治疗（仅高摄入量）。第四组中等摄入量组作为营养最佳的对照组。妊娠在妊娠第130天终止（每组6只），或让其足月分娩（每组8 - 10只）。在规定的治疗窗口期内，给予GH会提高母体血浆中GH、胰岛素、葡萄糖和非酯化脂肪酸的浓度，而尿素浓度降低。在第130天，GH治疗降低了母体肥胖评分、胴体脂肪百分比、内脏脂肪储存和瘦素浓度，主要是在高摄入量加晚期GH组。高摄入量组母羊的胎盘重量低于对照组，但与GH治疗无关。相比之下，晚期GH治疗可提高胎儿体重，并且这些胎儿的相对胴体脂肪含量、肾周脂肪量和肝糖原浓度高于所有其他组。母体营养摄入或GH对胎儿肾周脂肪中瘦素mRNA表达和胎儿血浆瘦素浓度没有显著影响。在足月分娩的妊娠中，与对照母羊相比，高摄入量组的妊娠期、胎儿胎盘质量和羔羊出生体重降低，但不受GH治疗的显著影响。总之，在妊娠早期和晚期给予外源性GH对母体内分泌、代谢和身体组成有深远影响。妊娠晚期治疗对胎儿生长有适度影响，与胎盘大小无关，对胎儿肥胖有深远影响，这可能对胎儿期以外的情况有影响。
