Preimplantation exposure to high insulin-like growth factor I concentrations results in increased resorption rates in vivo

BACKGROUND: Women with polycystic ovarian syndrome suffer increased rates of miscarriage. Elevated insulin and insulin-like growth factor I (IGF-I) concentrations have been implicated. Here, we hypothesize that the high concentrations of IGF-I result in miscarriage, represented by decreased normal p...

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Bibliographic Details
Published in:	Human reproduction (Oxford) Vol. 17; no. 2; pp. 457 - 462
Main Authors:	Pinto, A.B., Schlein, A.L., Moley, K.H.
Format:	Journal Article
Language:	English
Published:	Oxford Oxford University Press 01-02-2002
Subjects:	Animals apoptosis Biological and medical sciences Blastocyst - drug effects Blood - metabolism Culture Techniques Dose-Response Relationship, Drug Down-Regulation Fallopian Tubes - metabolism Female Female genital diseases Fetal Resorption - chemically induced Fetal Resorption - epidemiology Gynecology. Andrology. Obstetrics IGF-I IGF-IR Incidence Insulin-Like Growth Factor I - administration & dosage Insulin-Like Growth Factor I - metabolism Insulin-Like Growth Factor I - pharmacology Medical sciences Mice Mice, Inbred ICR mouse model Oligonucleotide Probes - pharmacology Oligonucleotides, Antisense - pharmacology Osmolar Concentration polycystic ovarian syndrome Pregnancy Pregnancy Outcome Receptor, IGF Type 1 - genetics Tumors apoptosis IGF-I IGF-IR mouse model polycystic ovarian syndrome Rodentia Resorption Female sterility Polycystic ovary Insulin like growth factor 1 In vitro Female genital diseases Pregnancy Embryo transfer In vivo Ovarian diseases Vertebrata Mammalia Ovum implantation Mouse Embryo culture Cyst Female Benign neoplasm Apoptosis Biological receptor
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Summary:	BACKGROUND: Women with polycystic ovarian syndrome suffer increased rates of miscarriage. Elevated insulin and insulin-like growth factor I (IGF-I) concentrations have been implicated. Here, we hypothesize that the high concentrations of IGF-I result in miscarriage, represented by decreased normal pregnancy rates and increased resorption rates in a mouse model. METHODS: In-vitro studies: 2-cell embryos were cultured in either 1.3 or 130 nmol/l IGF-I; or 500 nmol/l IGF-I receptor (IGF-IR) sense and antisense oligoprobes for 72 h. Embryos were then transferred into pseudo-pregnant ICR females. In-vivo studies: IGF-I-containing slow-release pellets or mock pellets were implanted within the uterine horn in ICR female mice. For both studies, the recipient females were killed on day 14.5 and the numbers of normal implantation sites versus resorption sites were recorded. RESULTS: In-vitro studies: blastocysts cultured in low IGF-I exhibited significantly higher normal implantation rates than blastocysts cultured in high IGF-I concentrations (P < 0.01). Blastocysts cultured in IGF-IR sense oligoprobes exhibited a significantly higher normal implantation rate than blastocysts cultured in antisense oligoprobes. In-vivo studies: mice implanted with IGF-I-containing pellets exhibited significantly lower normal implantation rates as compared with mock-pellet controls (P < 0.01). CONCLUSIONS: High preimplantation IGF-I concentrations in vitro or in vivo lead to increased resorption rates in the mouse.
Bibliography:	istex:ACFD34A4E81C421C4D3CF5593993A8D9C5A0B622 ark:/67375/HXZ-SKCT33KT-F local:0170457 PII:1460-2350
ISSN:	0268-1161 1460-2350 1460-2350
DOI:	10.1093/humrep/17.2.457