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Abstract

Superovulation causes detrimental effects, including embryonic loss and implantation failure. This study determined potential roles for insulin-like growth factor (IGF-I) in uterine environment regulation and preimplantation development, in conjunction with the detrimental effects of superovulation in the rat. IGF-I may be beneficial to preimplantation embryonic development. IGF-I stimulated embryonic development and metabolism in vitro and increased the rate of implantation and fetal development when the blastocysts were transferred into a receptive uterus. However, IGF-I may be involved in embryonic loss following superovulation, by perturbing the uterine environment. Superovulation enhanced uterine IGF-I action from day 1 to 3 of pregnancy and reduced its action on days 5 and 6. Uterine luminal fluid from the uterus exposed to increased IGF-I action from day 1 to 3 was detrimental to embryonic development. This uterine luminal fluid had altered electrolyte composition that is similar to that observed following superovulation. Anti-IGF-I antibody restored superovulationinduced alterations in cations, suggesting that IGF-I may partially mediate this effect of superovulation. Superovulation-induced alterations in IGF-I action may adversely affect decidualization, a critical step in implantation. High IGF-I levels from day 1 to 3 and low levels from day 3 to 5, inhibited deciduoma formation. Alterations in IGF-I action after day 5 had no effect, suggesting a role for IGF-I in uterine sensitization. The role of IGF-I in decidualization may be complex. IGF-I cannot be substituted for growth hormone (GH) and thyroxine (T4) during decidualization, but altered deciduoma formation and alkaline phosphatase (ALP) activity in the GH and T4-dependent manner. IGF-I either stimulated or inhibited deciduoma formation and ALP activity, depending upon concentration and treatment period. IGF-I stimulated basal ALP activity but inhibited prostaglandin E2-stimulated ALP activity in the endometrial stroma cells. In conclusion, IGF-I may play an important role in the maintenance of a receptive uterine environment for embryonic development and the regulation of decidualization. Embryonic loss and failure of implantation following superovulation may be partially attributed to disturbances in uterine IGF-I action as observed in this study.