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
| العنوان: | 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 |
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| المؤلفون: | Hyunjung Jade Lim, Sanjoy K. Das, Haengseok Song, Bibhash C. Paria, Sudhansu K. Dey |
| المصدر: | Molecular Endocrinology. 14:1147-1161 |
| بيانات النشر: | The Endocrine Society, 2000. |
| سنة النشر: | 2000 |
| مصطلحات موضوعية: | Vascular Endothelial Growth Factor A, Receptor, ErbB-4, Receptor, ErbB-2, medicine.medical_treatment, Endothelial Growth Factors, Leukemia Inhibitory Factor, Epithelium, Mice, Endocrinology, Pregnancy, reproductive and urinary physiology, Extracellular Matrix Proteins, Lymphokines, Nonmuscle Myosin Type IIB, Vascular Endothelial Growth Factors, General Medicine, Juxtacrine signalling, Growth Inhibitors, Cell biology, DNA-Binding Proteins, ErbB Receptors, Isoenzymes, medicine.anatomical_structure, Cytokine, Receptors, Estrogen, embryonic structures, Female, Steroids, Receptors, Progesterone, Cell Division, hormones, hormone substitutes, and hormone antagonists, endocrine system, medicine.medical_specialty, Stromal cell, Ovariectomy, Down-Regulation, Embryonic Development, Biology, Paracrine signalling, Internal medicine, medicine, Animals, Receptors, Growth Factor, Embryo Implantation, Blastocyst, Autocrine signalling, Molecular Biology, Homeodomain Proteins, Epidermal Growth Factor, Myosin Heavy Chains, Interleukin-6, urogenital system, Growth factor, Ovary, Uterus, Estrogen Receptor alpha, Membrane Proteins, Receptor Protein-Tyrosine Kinases, Mice, Mutant Strains, Homeobox A10 Proteins, Receptors, Vascular Endothelial Growth Factor, Gene Expression Regulation, Cyclooxygenase 2, Prostaglandin-Endoperoxide Synthases, Cyclooxygenase 1, Leukemia inhibitory factor |
| الوصف: | Various mediators, including cytokines, growth factors, homeotic gene products, and prostaglandins (PGs), participate in the implantation process in an autocrine, paracrine, or juxtacrine manner. However, interactions among these factors that result in successful implantation are not clearly understood. Leukemia inhibitory factor (LIF), a pleiotropic cytokine, was shown to be expressed in uterine glands on day 4 morning before implantation and is critical to this process in mice. However, the mechanism by which LIF executes its effects in implantation remains unknown. Moreover, interactions of LIF with other implantation-specific molecules have not yet been defined. Using normal and delayed implantation models, we herein show that LIF is not only expressed in progesterone (P4)-primed uterine glands before implantation in response to nidatory estrogen, it is also induced in stromal cells surrounding the active blastocyst at the time of the attachment reaction. This suggests that LIF has biphasic effects: first in the preparation of the receptive uterus and subsequently in the attachment reaction. The mechanism by which LIF participates in these events was addressed using LIF-deficient mice. We observed that while uterine cell-specific proliferation, steroid hormone responsiveness, and expression patterns of several genes are normal, specific members of the EGF family of growth factors, such as amphiregulin (Ar), heparin-binding EGF-like growth factor (HB-EGF), and epiregulin, are not expressed in LIF(−/−) uteri before and during the anticipated time of implantation, although EGF receptor family members (erbBs) are expressed correctly. Furthermore, cyclooxygenase-2 (COX-2), an inducible rate-limiting enzyme for PG synthesis and essential for implantation, is aberrantly expressed in the uterus surrounding the blastocyst in LIF(−/−) mice. These results suggest that dysregulation of specific EGF-like growth factors and COX-2 in the uterus contributes, at least partially, to implantation failure in LIF(−/−) mice. Since estrogen is essential for uterine receptivity, LIF induction, and blastocyst activation, it is possible that the nidatory estrogen effects in the P4-primed uterus for implantation are mediated via LIF signaling. However, we observed that LIF can only partially resume implantation in P4-primed, delayed implanting mice in the absence of estrogen, suggesting LIF induction is one of many functions that are executed by estrogen for implantation. |
| تدمد: | 1944-9917 0888-8809 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::31f655e795ef3e6e94e4587e2d38524fTest https://doi.org/10.1210/mend.14.8.0498Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....31f655e795ef3e6e94e4587e2d38524f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19449917 08888809 |
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