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Aberrant activation of LIF‐downstream signal caused decidualization failure in pseudopregnant mice
Author(s) -
Kimura T,
Nakamura H,
Koyama S,
Ogita K,
Tabata C,
Khan MH,
Tsutsui T,
Shimoya K,
Kaneda Y,
Murata Y
Publication year - 2006
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/j.1600-0897.2006.00383_5.x
Subject(s) - decidualization , decoy , uterus , andrology , endometrium , decidua , chemistry , knockout mouse , decidual cells , medicine , in vivo , endocrinology , placenta , biology , pregnancy , fetus , receptor , genetics , microbiology and biotechnology
As the leukemia inhibitory factor (LIF) knockout mice is infertile because of implantation failure, the downstream signals of LIF, such as STAT‐3, should play crucial roles for implantation. We have focused on the function of multifunctional transcription factors in endometrium during implantation window. We investigated here the effect of STAT‐3 decoy introduction into mouse uterus in vivo on pregnancy and decidualization. STAT‐3 decoy and scramble decoy were synthesized with phosphorotioate‐modification. On day 1.5 p.c., 80 μg decoy DNA+1000HAU HVJ‐E vector (GenomONE – Neo, Ishihara Sangyo, Osaka, Japan) suspension/horn was introduced into the uterine cavity. On day 5.0 p.c., implantation rate was determined by Evans blue injection. On day 3.5 p.c., 10 μL of sesame oil was injected single horn of pseudopregnant mice and fold‐increase of uterine wet weights was compared. Uterine morphology was examined by conventional Hematoxylin‐Eosin staining. Implantation rate was suppressed more than 70% in STAT‐3 decoy treated mice. In scramble decoy treated pseudopregnant mice, the uterine wet weight of infusion side was approximately 6.5‐fold of the control side. In STAT‐3 decoy infused mice, sesame oil induced ~2‐fold increase of the uterine wet weight. Histological examination indicated that decidualization of interstitial cells was apparently suppressed in the STAT‐3 decoy treated uterus, as compared with scramble decoy treated uteri. We revealed that in vivo transfection of STAT‐3 decoy into early pregnant mice uterus effectively inhibited implantation. The activation of STAT‐3 deeply concern with decidualization, which is one of very important steps to determine uterine receptivity.