Thomas A D, Murray J D, Famula T R, Oberbauer A M
Department of Animal Science, University of California, Davis, CA 95616-8521, USA.
Reproduction. 2001 Oct;122(4):537-44. doi: 10.1530/rep.0.1220537.
Female mice carrying a regulatable growth hormone transgene (oMt1a-oGH) are subfertile when the transgene is actively expressed. This study was designed to characterize subfertility caused by increased concentrations of growth hormone. In particular, this study aimed to: (i) determine the effects of transgene activation and inactivation on mating, conception, maintenance of pregnancy, ovulation rate, litter characteristics and embryonic survival at day 17 of pregnancy, (ii) characterize oestrous cyclicity in transgenic versus wild-type female mice, and (iii) correlate corticosterone concentrations with transgene expression and reproductive performance. Transgenic and wild-type female mice were allocated randomly to one of four treatment groups at weaning: (i) transgenic female mice that always express the transgene, (ii) transgenic female mice that never express the transgene, (iii) transgenic female mice that express the transgene for up to 8 weeks of age and (iv) non-transgenic wild-type female mice receiving the transgene stimulus until 8 weeks of age. Activation followed by inactivation of the transgene resulted in an increased incidence of remating, resulting in an extended interval to establish pregnancy in comparison with all other treatment groups. Transgenic mice that always expressed the transgene and those that expressed the transgene for up to 8 weeks of age had lower pregnancy rates and higher ovulation rates compared with mice from other treatment groups. Both embryonic survival and the duration of the oestrous cycle did not differ among treatment groups. Active expression of the transgene resulted in an increase in the plasma concentration of corticosterone, which was associated with reduced fertility. These data indicate that the presence of a high growth hormone concentration impedes the establishment and maintenance of pregnancy. Increased plasma corticosterone concentrations may interfere with implantation as well as potentiate leptin resistance, which has been reported previously in studies with these mice.
携带可调控生长激素转基因（oMt1a - oGH）的雌性小鼠在转基因活跃表达时生育力低下。本研究旨在表征由生长激素浓度升高导致的生育力低下。具体而言，本研究旨在：（i）确定转基因激活和失活对交配、受孕、维持妊娠、排卵率、窝仔特征以及妊娠第17天胚胎存活率的影响，（ii）表征转基因与野生型雌性小鼠的发情周期，以及（iii）将皮质酮浓度与转基因表达和生殖性能相关联。转基因和野生型雌性小鼠在断奶时被随机分配到四个处理组之一：（i）始终表达转基因的转基因雌性小鼠，（ii）从不表达转基因的转基因雌性小鼠，（iii）在8周龄前表达转基因的转基因雌性小鼠，以及（iv）接受转基因刺激直至8周龄的非转基因野生型雌性小鼠。转基因激活后再失活导致再次交配的发生率增加，与所有其他处理组相比，建立妊娠的间隔时间延长。与其他处理组的小鼠相比，始终表达转基因的转基因小鼠以及在8周龄前表达转基因的小鼠妊娠率较低，排卵率较高。各处理组之间胚胎存活率和发情周期持续时间均无差异。转基因的活跃表达导致皮质酮血浆浓度升高，这与生育力降低有关。这些数据表明，高生长激素浓度的存在会阻碍妊娠的建立和维持。血浆皮质酮浓度升高可能会干扰着床，并增强瘦素抵抗，这在先前对这些小鼠的研究中已有报道。
