The effect of intrauterine copper and other metals on implantation in rats and hamsters.
About: This article is published in Fertility and Sterility.The article was published on 1970-03-01. It has received 86 citations till now. The article focuses on the topics: Copper.
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TL;DR: By means of neutron activation analysis, the concentrations of copper, zinc, manganese, sodium and potassium were estimated in the endometrium and cervical mucus in sixteen women using the Cu-T device and the daily release of copper from the device is almost constant during one year.
140 citations
TL;DR: The burst release of lethal concentration of Cu ions from TCu380A, especially at the implant site, is a cause of concern, and it is advisable to use TCuIUD designs that release Cu ions within cytotoxic limits yet therapeutic, similar to TCu220C.
Abstract: Sustained release of copper (Cu) ions from Cu-containing intrauterine devices (CuIUD) is quite efficient for contraception. However, the tissue surrounding the CuIUD is exposed to toxic Cu ion levels. The objective for this study was to quantify the concentration dependent cytotoxic effects of Cu ions and correlate the toxicity due to Cu ion burst release for two popular T-shaped IUDs - TCu380A and TCu220C on L929 mouse fibroblasts. Fibroblasts were cultured in 98 well tissue culture plates and 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphehyltetrazolium bromide (MTT) assay was used to determine their viability and proliferation as a function of time. For cell seeding numbers ranging from 10,000 to 100,000, a maximum culture time of 48 h was identified for fibroblasts without significant reduction in cell proliferation due to contact inhibition. Thus, for Cu cytotoxicity assays, a cell seeding density of 50,000 and a maximum culture time of 48 h in 96 well plates were used. 24 h after cell seeding, culture media were replaced with Cu ion containing media solutions of different concentrations, including 24 and 72 h extracts from TCuIUDs and incubated for a further 24 h. Cell viability decreased with increasing Cu ion concentration, with 30 % and 100 % reduction for 40 μg/ml and 100 μg/ml respectively at 24 h. The cytotoxic effects were further evaluated using light microscopy, apoptosis and cell cycle analysis assays. Fibroblasts became rounded and eventually detached from TCP surface due to Cu ion toxicity. A linear increase in apoptotic cell population with increasing Cu ion concentration was observed in the tested range of 0 to 50 μg/ml. Cell cycle analysis indicated the arrest of cell division for the tested 25 to 50 μg/ml Cu ion treatments. Among the TCuIUDs, TCu220C having 265 mm2 Cu surface area released 9.08 ± 0.16 and 26.02 ± 0.25 μg/ml, while TCu380A having 400 mm2 released 96.7 ± 0.11 and 159.3 ± 0.15 μg/ml respectively following 24 and 72 h extractions. The effects of TCuIUD extracts on viability, morphology, apoptosis and cell cycle assay on L929 mouse fibroblasts cells, were appropriate for their respective Cu ion concentrations. Thus, a concentration of about 46 μg/ml (~29 μM) was identified as the LD50 dose for L929 mouse fibroblasts when exposed for 24 h based on our MTT cell viability assay. The burst release of lethal concentration of Cu ions from TCu380A, especially at the implant site, is a cause of concern, and it is advisable to use TCuIUD designs that release Cu ions within cytotoxic limits yet therapeutic, similar to TCu220C.
101 citations
87 citations
TL;DR: In this article, the effect of copper ion (Cu2+) in preventing pregnancy was evaluated in the presence of 10 ng, 1 microgram, 10 microgram or 100 micrograms of Cu2+ in BWW culture medium, and the motility, viability, acrosome reaction (AR) and the capacity to penetrate zona-free hamster eggs were assessed at 5 h of incubation.
Abstract: The objective of this study is to provide additional information on the effect of copper ion (Cu2+) in preventing pregnancy. Human spermatozoa, selected by the swim-up method, were incubated for 0, 5 or 24 h in the presence of 10 ng, 1 microgram, 10 micrograms or 100 micrograms of Cu2+ mL-1 in BWW culture medium, and then evaluated in terms of their motility, viability, acrosome reaction (AR) and the capacity to penetrate zona-free hamster eggs. AR and penetration in zona-free hamster eggs were assessed at 5 h of incubation. Motility, viability and AR in sperm incubated for 5 h were significantly affected by Cu2+ at a concentration of 100 micrograms mL-1, but not at the lower concentrations. Incubation for 24 h did not affect motility and viability of sperm incubated in the presence of concentrations of Cu2+ ranging from 10 ng mL-1 to 10 micrograms mL-1, but a concentration of 100 micrograms mL-1 caused a significant decrease in both parameters. In contrast, the penetration rate of zona-free hamster oocytes significantly decreased compared with that of controls, when only sperm were incubated in the presence of concentrations of Cu2+ ranging from 10 ng mL-1 to 10 micrograms mL-1, and no penetration was observed in the presence of 100 micrograms mL-1 of Cu2+ . When only oocytes were exposed to Cu2+, the penetration rate dropped to 50% of that of the controls. Finally, when both gametes were exposed to Cu2+ before co-incubation, the penetration rate fell to zero for every concentration tested. Results showed that copper, at concentrations similar to those released from intrauterine devices (IUD), affects the fertilizing capacity of human gametes in vitro and interferes with the sperm-oocyte interaction leading to fertilization. These effects suggest that the principle action of Cu2+ released from Cu-IUD is to act as a preconception contraceptive agent when delivered in endometrial and oviducal fluids.
83 citations
TL;DR: The antifertility effect of intrauterine copper in the rat seems to be due to a local change in the intrauterne environment such that the blastocyst does not implant.
82 citations
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TL;DR: Reductions in both expulsion and removal rates of TCu because of medical reasons constituted the principal factors accounting for the continuation rate of 77.6 as compared with 65.6 for loop D at the end of 2 years of use.
217 citations
23 citations
TL;DR: An intrauterine device in one rat uterine horn causes an increased incidence of embryonic death in the contralateral horn.
Abstract: SummaryAn intrauterine device in one rat uterine horn causes an increased incidence of embryonic death in the contralateral horn.
5 citations