以连续浸提法研究铜宫内节育器的大鼠致畸敏感期生殖毒性

The reproductive toxicity of rat models implanted with copper-bearing intrauterine device at teratogenic sensitive period by continuous extraction method

背景:铜宫内节育器是目前中国常用的宫腔内植入避孕三类医疗器械,在长期植入后意外怀孕或停止使用后短期内怀孕的情况下,是否对胚胎或胎儿有影响尚无明确结论。目的:通过观察大鼠致畸敏感期尾静脉注射铜宫内节育器浸提液对孕鼠和胎鼠的影响,评价铜宫内节育器的安全性。方法:将60只雌性妊娠SD大鼠随机均分为对照组、高剂量组、中剂量组与低剂量组,高、中、低剂量组从妊娠的第1天开始分别尾静脉注射浸提比例为0.2,0.1,0.05 g/mL的铜宫内节育器浸提液,每日注射量是0.01 mL/g,对照组给予同体积的生理盐水,连续注射20 d。20 d后处死孕鼠,测量体质量,检查两侧子宫和内脏器官,分离胎鼠,记录子宫与胎鼠质量、黄体数、着床数、死胎、活胎和吸收胎等;记录胎鼠体质量、身长、尾长、枕骨骨化程度及外观、骨骼、内脏的异常情况。结果与结论:高、中、低剂量组的窝数、着床数、活胎数、黄体数、活胎率、死胎率、子宫连胎质量、吸收胎数与对照组比较差异无显著性意义(P>0.05),各组孕鼠内脏无畸形及异常。高、中、低剂量组胎鼠身长、尾长、体质量、上枕骨骨化率与对照组比较差异无显著性意义(P>0.05),胎鼠外观、骨骼、内脏无畸形及异常。表明在致畸敏感期大鼠静脉注射铜宫内节育器浸提液后,未见母体毒性、胚胎生长发育异常及胎鼠畸形及其他胚胎毒性。

BACKGROUND：At present, the copper-bearing intrauterine device, a kind of class III medical devices, is commonly used in China. However, there is no clear conclusion about whether it has impact on the embryo or fetus in some cases, such as unexpected pregnancy during long-term implantation and pregnancy in a short time after removing it. OBJECTIVE： To evaluate the safety of copper-bearing intrauterine device by observing the influence of copper-bearing intrauterine device extracts on pregnant rats and rat fetuses by tail vein injection in the sensitive period of teratogenesis. METHODS： A total of 60 fertilized rats were divided into control group, high dosage group, middle dosage group, and low dosage group. The copper-bearing intrauterine device extracts were prepared by the continuous extraction method. Different concentrations （0.2, 0.1, 0.05 g/mL） of copper-bearing intrauterine device extracts were injected by the tail vein at the 1st day of pregnancy in the latter three groups at a dosage of 0.01 mL/g per day. The control group was given the same amount of normal saline. The injection lasted for 20 days. Then, the pregnant rats were sacrificed to measure body mass, check both sides of the uterus and internal organs, isolate fetal rats, as wel as record the quality of uterus and fetal rats, corpus luteum, implantation numbers, the number of stilbirths, then number of live births and the number of fetal absorption. The fetal rats were determined in the folowing aspects： body mass, body height, tail length, the ossification degree and appearance of the occipital bone, bone and visceral anomalies. RESULTS AND CONCLUSION： The number of births, implantation numbers, the number of live births, the number of corpus luteum, the percentages of live births and stilbirths, the number of resorbed fetuses, and the weight of uterus and fetal rats in the control group showed no difference from those in the other three groups （P 〉 0.05）. No malformation in the internal organs occurred. Compared with the control group, the high, middle and low dosage groups showed no difference in the height, tail length, body mass, and ossification degree of the occipital bone of fetal rats （P 〉 0.05）. No malformation in the appearance, skeleton and internal organs occurred in the fetal rats. These findings indicate that there were no maternal toxicity, abnormal embryonic growth or rat fetus anomalies after injecting copper-bearing intrauterine device extracts into pregnant rats in sensitive period of teratogenesis.