Leukemia inhibitory factor ligand-receptor signaling is important for uterine receptivity and implantation in golden hamsters (Mesocricetus auratus).

Blastocyst implantation occurs in the progesterone-primed uterus of hamsters, but not in mice where the progesterone-primed uterus requires estrogen influence. Leukemia inhibitory factor (Lif), an estrogen-regulated gene in mice, is an absolutely needed cytokine for uterine receptivity and implantation in this species. This study aimed to evaluate the importance of Lif ligand-receptor signaling during uterine receptivity and implantation in hamsters. We investigated whether or not the uterine expression patterns of Lif and its receptors, Lif-r and gp130, during the periimplantation period of pregnancy and its hormonal regulation in the ovariectomized hamster correlate with some of the vital phases of uterine changes during early pregnancy. Uterine Lif, Lif-r, and gp130 mRNA expressions were examined by Northern and in situ hybridization. During the uterine preparatory phase for implantation, Lif, Lif-r, and gp130 were expressed either in the gland, luminal epithelium or both. As the implantation process began, Lif expression was minimal, but Lif-r and gp130 extended to the decidual areas. This decidual expression of Lif-r and gp130 was not dependent on the presence of the embryo since these genes were expressed in the suture-induced deciduomata. We also observed that, while the uterine Lif was induced by estrogen, Lif-r and gp130 were induced by progesterone in ovariectomized hamsters. Additionally, we show that a Lif antibody when instilled intraluminally on day 3 of pregnancy reduced the number of implantation sites. Taken together, these data suggest that Lif signaling is important for uterine receptivity and implantation in hamsters.

[1]  B. Paria,et al.  Importance of uterine cell death, renewal, and their hormonal regulation in hamsters that show progesterone-dependent implantation. , 2006, Endocrinology.

[2]  H. Lim,et al.  Evidence for heterodimeric association of leukemia inhibitory factor (LIF) receptor and gp130 in the mouse uterus for LIF signaling during blastocyst implantation. , 2006, Reproduction.

[3]  F. Zegers-Hochschild,et al.  Luteal estrogen is not required for the establishment of pregnancy in the human , 1995, Journal of Assisted Reproduction and Genetics.

[4]  J. Morrow,et al.  Prostaglandin E2 Is a Product of Induced Prostaglandin-endoperoxide Synthase 2 and Microsomal-type Prostaglandin E Synthase at the Implantation Site of the Hamster* , 2004, Journal of Biological Chemistry.

[5]  H. M. Beier,et al.  The cytokine receptor gp130 and its soluble form are under hormonal control in human endometrium and decidua. , 2004, Molecular human reproduction.

[6]  Y. Hsieh,et al.  Leukemia Inhibitory Factor Expression in Different Endometrial Locations Between Fertile and Infertile Women Throughout Different Menstrual Phases , 2000, Journal of Assisted Reproduction and Genetics.

[7]  C. Stewart,et al.  Control of Uterine Receptivity and Embryo Implantation by Steroid Hormone Regulation of LIF Production and LIF Receptor Activity: Towards a Molecular Understanding of “The Window of Implantation” , 2004, Reviews in Endocrine and Metabolic Disorders.

[8]  K. Dahlman-Wright,et al.  Identification of Estrogen‐Regulated Genes of Potential Importance for the Regulation of Trabecular Bone Mineral Density , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[9]  Zeng-Ming Yang,et al.  Expression of leukemia inhibitory factor receptor and gp130 in mouse uterus during early pregnancy , 2002, Molecular reproduction and development.

[10]  Haibin Wang,et al.  Dual source and target of heparin-binding EGF-like growth factor during the onset of implantation in the hamster. , 2002, Development.

[11]  Jeff Reese,et al.  Deciphering the Cross-Talk of Implantation: Advances and Challenges , 2002, Science.

[12]  L. Robb,et al.  Cloning of rat interleukin 11 and interleukin 11 receptor alpha chain and analysis of their expression in rat uterus in the peri-implantation period. , 2001, Reproduction.

[13]  W. Alvord,et al.  Dual control of LIF expression and LIF receptor function regulate Stat3 activation at the onset of uterine receptivity and embryo implantation , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[14]  L. Robb,et al.  Expression of interleukin-11 during the human menstrual cycle: coincidence with stromal cell decidualization and relationship to leukaemia inhibitory factor and prolactin. , 2000, Molecular human reproduction.

[15]  S. Dey,et al.  Dysregulation of EGF family of growth factors and COX-2 in the uterus during the preattachment and attachment reactions of the blastocyst with the luminal epithelium correlates with implantation failure in LIF-deficient mice. , 2000, Molecular endocrinology.

[16]  T. Modric,et al.  Pregnancy-dependent expression of leukaemia inhibitory factor (LIF), LIF receptor-beta and interleukin-6 (IL-6) messenger ribonucleic acids in the porcine female reproductive tract. , 2000, Placenta.

[17]  Y. S. Yang,et al.  Expression of leukemia inhibitory factor and its receptor in preimplantation embryos. , 1999, Fertility and sterility.

[18]  S. Dey,et al.  Embryo Implantation , 1999, Proceedings in the Serono Symposia USA Series.

[19]  D. Roopenian,et al.  Maternal IL-11Ralpha function is required for normal decidua and fetoplacental development in mice. , 1998, Genes & development.

[20]  C. Begley,et al.  Infertility in female mice lacking the receptor for interleukin 11 is due to a defective uterine response to implantation , 1998, Nature Medicine.

[21]  M. Koyama,et al.  Human decidual cell biosynthesis of leukemia inhibitory factor: regulation by decidual cytokines and steroid hormones. , 1997, Biology of reproduction.

[22]  J. Nichols,et al.  Complementary tissue-specific expression of LIF and LIF-receptor mRNAs in early mouse embryogenesis , 1996, Mechanisms of Development.

[23]  J. Pollard,et al.  Leukemia inhibitory factor (LIF) and LIF receptor expression in human endometrium suggests a potential autocrine/paracrine function in regulating embryo implantation. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[24]  H. Kliman,et al.  The effect of leukemia inhibitory factor (LIF) on trophoblast differentiation: a potential role in human implantation. , 1996, The Journal of clinical endocrinology and metabolism.

[25]  K. Shiota,et al.  Targeted disruption of gp130, a common signal transducer for the interleukin 6 family of cytokines, leads to myocardial and hematological disorders. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[26]  I. Sargent,et al.  Leukaemia inhibitory factor significantly enhances the blastocyst formation rates of human embryos cultured in serum-free medium. , 1996, Human reproduction.

[27]  R. Casper,et al.  Recombinant human leukemia inhibitory factor does not enhance in vitro human blastocyst formation. , 1995, Fertility and sterility.

[28]  Stephen K. Smith,et al.  Stage-specific expression of cytokine and receptor messenger ribonucleic acids in human preimplantation embryos. , 1995, Biology of reproduction.

[29]  C. Ware,et al.  Targeted disruption of the low-affinity leukemia inhibitory factor receptor gene causes placental, skeletal, neural and metabolic defects and results in perinatal death. , 1995, Development.

[30]  T. Kameda,et al.  Leukemia inhibitory factor produced at the fetomaternal interface stimulates chorionic gonadotropin production: its possible implication during pregnancy, including implantation period. , 1995, The Journal of clinical endocrinology and metabolism.

[31]  C. Begley,et al.  Cloning of a murine IL‐11 receptor alpha‐chain; requirement for gp130 for high affinity binding and signal transduction. , 1994, The EMBO journal.

[32]  D. Ghosh,et al.  Luteal phase ovarian oestrogen is not essential for implantation and maintenance of pregnancy from surrogate embryo transfer in the rhesus monkey. , 1994, Human reproduction.

[33]  T. Inoue,et al.  Expression of leukemia inhibitory factor in human endometrium and placenta. , 1994, Biology of reproduction.

[34]  S. Dey,et al.  Blastocyst's state of activity determines the "window" of implantation in the receptive mouse uterus. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[35]  D. Gearing The leukemia inhibitory factor and its receptor. , 1993, Advances in immunology.

[36]  C. Stewart,et al.  Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor , 1992, Nature.

[37]  Comeau,et al.  The IL-6 signal transducer, gp130: an oncostatin M receptor and affinity converter for the LIF receptor. , 1992, Science.

[38]  D. Hilton LIF: lots of interesting functions. , 1992, Trends in biochemical sciences.

[39]  C. Stewart,et al.  Uterine expression of leukemia inhibitory factor coincides with the onset of blastocyst implantation. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[40]  Austin G Smith,et al.  Differentiation inhibiting activity is produced in matrix-associated and diffusible forms that are generated by alternate promoter usage , 1990, Cell.

[41]  F. Lee,et al.  The genes for leukemia inhibitory factor and interleukin-6 are expressed in mouse blastocysts prior to the onset of hemopoiesis , 1990, Molecular and cellular biology.

[42]  F. Conquet,et al.  Developmental expression of myeloid leukemia inhibitory factor gene in preimplantation blastocysts and in extraembryonic tissue of mouse embryos , 1990, Molecular and cellular biology.

[43]  S. Sholl,et al.  Estrogen synthesis and metabolism in the hamster blastocyst, uterus and liver near the time of implantation. , 1983, Journal of steroid biochemistry.

[44]  S. Dey,et al.  Aromatase activity in the rabbit blastocyst. , 1982, Journal of reproduction and fertility.

[45]  R. Heap,et al.  Embryonic Signals and Maternal Recognition , 1981 .

[46]  J. D. Wilson,et al.  Estrogen formation in the early rabbit embryo. , 1978, Science.

[47]  S. Dey,et al.  A new concept: control of early pregnancy by steroid hormones originating in the preimplantation embryo. , 1976, Vitamins and hormones.

[48]  G. S. Greenwald,et al.  Plasma levels of oestrogen and progesterone in pregnant and lactating hamsters. , 1974, The Journal of endocrinology.

[49]  J. S. Perry,et al.  Steroid Hormone Production by Pig Blastocysts , 1973, Nature.

[50]  G. S. Greenwald,et al.  Peripheral levels of estrogen in the cyclic hamster. , 1973, Endocrinology.

[51]  W. W. Leavitt,et al.  Circulating progesterone levels in the golden hamster during the estrous cycle, pregnancy, and lactation. , 1970, Biology of reproduction.

[52]  M. Harper,et al.  Implantation and embryonic development in the ovariectomized-adrenalectomized hamster. , 1969, Biology of reproduction.

[53]  C. E. Adams,et al.  Delayed implantation in the spayed, progesterone treated adult mouse. , 1966, Journal of reproduction and fertility.

[54]  R. K. Meyer,et al.  Effect of Varying Doses of Progesterone on Implantation in the Ovariectomized Hamster.∗ , 1962 .

[55]  R. K. Meyer,et al.  Nidation in Progesterone-Treated, Estrogen-Deficient Hamsters, Mesocricetus auratus (Waterhouse).∗ , 1960, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[56]  R. Deanesly Normal Implantation in Ovariectomized Guinea Pigs , 1960, Nature.