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The role for insulin-like growth factor-I in preimplantation embryonic development and decidualization following superovulation in the rat

University of British Columbia

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.

Thesis/Dissertation

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2009-02-19

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http://hdl.handle.net/2429/4814

Reproductive and Developmental Sciences

University of British Columbia

UBCV

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