Development of pre-implantation mouse embryos under the influence of pineal indoles

The developmental toxicity of pineal hormones on mouse embryos was examined both in vitro and in vivo. Pregnant ICR mice were divided into groups which received at 1.5 days post-coitum (p.c.) and again at 2.5 days p.c. a subcutaneous injection of one of the following pineal indoles: hydroxyindoleacetic acid (HIAA), melatonin (MEL), methoxytryptophol (MTP) or methoxytryptamine (MTA). Mice treated with the injection vehicle served as the control. The animals were sacrificed at 17.5 days p.c. The pineal indole treatment did not cause changes in the gravid uterine weight, numbers of implants, early resorption, late resorption, dead fetuses and live fetuses, fetal weight or fetal crown-rump length, and did not produce embryos with external or visceral defects. However, some mice treated with MTP or MTA produced litters in which all embryos underwent resorption. Cultured embryos at the 4-cell stage were treated with the aforementioned pineal indoles and examined after 24, 48, 72 and 96 hours. It was found that MTA retarded embryonic development at all time points studied. HIAA also produced a slight inhibitory effect on embryonic development. Some embryos underwent degeneration in response to the MTA and HIAA treatments. However, MEL- and MTP-treated embryos were in general developmentally similar to control embryos. When cultured embryos were treated at the 8-cell to compacting stage, it was found that MTA exerted only a slight retarding effect on embryonic development, while other indoles were devoid of any conspicuous effects.