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

doi:10.3969/j.issn.2095-4344.2014.34.019

Abstract

Abstract:

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 well as record the quality of uterus and fetal rats, corpus luteum, implantation numbers, the number of stillbirths, then number of live births and the number of fetal absorption. The fetal rats were determined in the following 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 stillbirths, 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.

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

全文链接：

Key words: intrauterine devices, copper, preconception injuries, rats

CLC Number:

R318

Zhang Dan-dan, Wang Yi, Wang Chun-ren, Wang Zhao-xu. The reproductive toxicity of rat models implanted with copper-bearing intrauterine device at teratogenic sensitive period by continuous extraction method[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(34): 5520-5524.

Figures/Tables 1

2.1 实验动物数量分析 60只孕鼠均进入结果分析。 2.2 孕鼠检查孕鼠尾静脉注射铜宫内节育器浸提液，连续给药20次未见动物异常反应。大鼠孕期无阴道流血、流产等异常现象。与对照组比较，各受试组动物在孕期D0、D3、D6、D9、D12、D15、D18、D20体质量与对照组比较差异无显著性意义。计算孕鼠体质量净增长结果显示各实验组与对照组比较差异无显著性意义。妊娠20 d处死孕鼠解剖检查，未见各组孕鼠有特征性内脏畸形和异常。铜宫内节育器对孕鼠生殖功能的影响：由表1可见，宫腔形宫内节育器浸提液受试组与对照组比较，未见其对大鼠生殖功能有明显影响。3个受试组孕鼠的平均着床数、窝平均活胎数、平均黄体数、活胎率、死胎率及子宫连胎质量与对照组比较差异均无显著性意义(P > 0.05)。各受试组吸收胎率与对照组比较未见显著升高。铜宫内节育器浸提液各受试组平均胎盘质量与对照组比较未见明显降低。 2.3 胎鼠检查宫腔形宫内节育器对胚胎生长发育的影响：由表2可见，铜宫内节育器浸提液各组胎鼠身长、尾长与对照组比较未见显著性差异，铜宫内节育器浸提液各组胎鼠平均体质量与对照组比较差异无显著性意义(P > 0.05)。对胎鼠外观、骨骼及内脏进行检查，共443只。对照组和各受试组未见皮下出血和其他外观畸形。对224只胎鼠进行骨骼检查，结果见表3。上枕骨检查结果显示，各受试组与对照组骨化率比较差异无显著性意义，实验结果表明宫腔形宫内节育器对胎鼠骨骼骨化无不良影响。各组胎鼠外观、骨骼、内脏检查情况：对照组、低剂量组、中剂量组、高剂量组检测窝数分别为10，9，9，8，胎鼠数分别为121，107，116，99只，异常数与异常率均为0(外观异常主要表现为皮下出血)；骨骼检查的胎鼠数分别为61，56，57，50只，异常数与异常率均为0(骨骼异常主要表现为第五胸骨缺失)；内脏检查的胎鼠数分别为60，51，59，49只，异常数与内脏畸形率均为0。内脏检查胎鼠共219只，各组内脏未发现畸形。显著性检验各给药组外观、骨骼异常率、内脏畸形率与对照组差异无显著性意义(P > 0.05)。"

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