The zinc contraceptive effect: targets, timing, and quantitative thresholds.

There is a critical need for novel non-hormonal contraceptives. Zinc-based intrauterine devices (IUDs) demonstrate 100% efficacy in rats, yet the mechanism remains unclear. We investigated whether zinc targets sperm, embryos, or the endometrium. Rats with zinc, copper, or nylon IUDs were mated. All retrieved embryos were fertilised, indicating no primary spermicidal effect. However, embryos from rats with a zinc IUD failed to reach the blastocyst stage, unlike those from rats with a copper IUD. In vitro embryo culture confirmed that zinc significantly inhibited mouse embryo development in a dose-dependent manner, with 5 μg/ml zinc causing a 97% decrease in blastocyst formation, whilst copper caused a 61% decrease. Surviving zinc-treated embryos also had significantly reduced attachment to human endometrial cells, unlike copper-treated embryos. There was also no reduced attachment of untreated mouse embryos to zinc- and copper-treated endometrial cells. These findings suggest that zinc's primary contraceptive mechanism is the potent inhibition of pre-implantation embryo development.