Background It is believed that estrogen plays pivotal roles in the regulation of follicle/oocyte maturation and oocyte fertilizability. It is also involved in the functional preparation of the fallopian tubes for sub...Background It is believed that estrogen plays pivotal roles in the regulation of follicle/oocyte maturation and oocyte fertilizability. It is also involved in the functional preparation of the fallopian tubes for subsequent gamete interaction, in early embryonic development occurring in the tubal microenvironment, and in the preparation of the uterus for implantation. This study was designed to determine whether estrogen is required for follicular and embryonic development. Methods The biosynthesis of estrogen was blocked by a daily injection of the aromatase inhibitor, Arimidex, at a dose of 100 μg/d, using 3-4 week old C57B6 F1 female mice. Injections were continued for 3 days in experiment 1 (n=10) and for 5 days in experiment 2 (n=23). Mice in the control group (n=27) were given the same amount of saline. Exogenous gonadotrophin [7.5 IU pregnant mare serum gonadotrophin (PMSG)] was administered to induce follicular growth and development on the second day. In experiment 1, we tested estrogen and progesterone levels and examined ovary morphology two days later. In experiment 2, 47 hours after PMSG injection, 5 IU human chorionic gonadotropin (hCG) was given and two female mice were then caged with a male mouse overnight. Two days later, we measured estrogen and progesterone levels. We then removed the embryos, cultured them, and examined embryonic development every 24 hours for 3 days. Results Before hCG injection, estrogen levels in mice from the Arimidex group were suppressed by 94%, and progesterone levels were suppressed by 75%. There was no difference between the two groups in mean number of total follicles found per animal (30.4 follicles/animal in the control group and 27 follicles/animal in the Arimidex group). Two days after hCG injection, estrogen levels in the Arimidex group were significantly lower than that in the control group (P<0.01), while progesterone levels were not significantly lower (P>0.05). The rate of development of embryos, morulae, blastocysts, and hatching blastocysts was not significantly different between the two groups (P=0.20, 0.10, 0.44, and 0.38, respectively).Conclusions In the present study, by depriving mice of normal estrogen support, we have been able to rule out the absolute need for rising levels of estrogen for the completion of the follicular maturation process and the development of embryos in vitro.展开更多
目的评价新橙皮苷对大鼠胚胎-胎仔发育的毒性。方法妊娠大鼠根据妊娠第0天(gestation day 0,GD0)和体质量采用分层随机法分成5组:对照(0.5%羧甲基纤维素钠)组,环磷酰胺(12 mg·kg^(-1))组,新橙皮苷低、中、高(0.45,0.9,1.8g·kg...目的评价新橙皮苷对大鼠胚胎-胎仔发育的毒性。方法妊娠大鼠根据妊娠第0天(gestation day 0,GD0)和体质量采用分层随机法分成5组:对照(0.5%羧甲基纤维素钠)组,环磷酰胺(12 mg·kg^(-1))组,新橙皮苷低、中、高(0.45,0.9,1.8g·kg^(-1))3个剂量组。妊娠鼠于GD6开始给药至GD15。实验期间,每周至少测定2次体质量和1次摄食量。GD20处死妊娠鼠,对黄体、着床腺、胎仔、胎盘等情况进行检查。结果试验期间,各组动物临床症状观察均未见明显异常。与对照组相比,新橙皮苷各剂量组动物体质量未见明显改变,环磷酰胺组动物增重减缓;新橙皮苷各剂量组黄体、着床、活胎、吸收胎、死胎计数均未见明显改变,环磷酰胺组子宫重量下降;新橙皮苷高剂量组胎仔身长降低,环磷酰胺组身长、尾长、重量及胎盘重均降低;新橙皮苷各剂量组胎仔外观检查未见给药相关改变,环磷酰胺组主要可见全身浮肿、头、耳、面、肢、指趾等改变。胎仔内脏检查中,新橙皮苷各剂量组分别可见1例脑室改变,中、高剂量组分别可见2例和1例食管扩张;环磷酰胺组可见腭、脑室、食管、睾丸附睾等改变。骨骼检查中,新橙皮苷可延缓顶骨、胸骨的骨化,可能影响下颌骨、颈椎、腰椎、耻骨、枕骨和肋骨的骨化。环磷酰胺12mg·kg^(-1)对颅骨、脊椎骨、肋骨、胸骨、掌骨等的骨化均有所影响。结论新橙皮苷给药后,对母体未产生明显毒性反应,未观察到临床不良反应的剂量水平(NOAEL)为1.8 g·kg^(-1);对胚胎-胎仔的发育毒性主要表现为延缓骨骼如顶骨、胸骨等的骨化外,还可能影响脑部和食管的发育,NOAEL<0.45 g·kg^(-1)。展开更多
文摘Background It is believed that estrogen plays pivotal roles in the regulation of follicle/oocyte maturation and oocyte fertilizability. It is also involved in the functional preparation of the fallopian tubes for subsequent gamete interaction, in early embryonic development occurring in the tubal microenvironment, and in the preparation of the uterus for implantation. This study was designed to determine whether estrogen is required for follicular and embryonic development. Methods The biosynthesis of estrogen was blocked by a daily injection of the aromatase inhibitor, Arimidex, at a dose of 100 μg/d, using 3-4 week old C57B6 F1 female mice. Injections were continued for 3 days in experiment 1 (n=10) and for 5 days in experiment 2 (n=23). Mice in the control group (n=27) were given the same amount of saline. Exogenous gonadotrophin [7.5 IU pregnant mare serum gonadotrophin (PMSG)] was administered to induce follicular growth and development on the second day. In experiment 1, we tested estrogen and progesterone levels and examined ovary morphology two days later. In experiment 2, 47 hours after PMSG injection, 5 IU human chorionic gonadotropin (hCG) was given and two female mice were then caged with a male mouse overnight. Two days later, we measured estrogen and progesterone levels. We then removed the embryos, cultured them, and examined embryonic development every 24 hours for 3 days. Results Before hCG injection, estrogen levels in mice from the Arimidex group were suppressed by 94%, and progesterone levels were suppressed by 75%. There was no difference between the two groups in mean number of total follicles found per animal (30.4 follicles/animal in the control group and 27 follicles/animal in the Arimidex group). Two days after hCG injection, estrogen levels in the Arimidex group were significantly lower than that in the control group (P<0.01), while progesterone levels were not significantly lower (P>0.05). The rate of development of embryos, morulae, blastocysts, and hatching blastocysts was not significantly different between the two groups (P=0.20, 0.10, 0.44, and 0.38, respectively).Conclusions In the present study, by depriving mice of normal estrogen support, we have been able to rule out the absolute need for rising levels of estrogen for the completion of the follicular maturation process and the development of embryos in vitro.
