Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-04848-8
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Funding
- Eunice Kennedy Shriver National Institute of Child Health and Development [R21 HD076347, R01 HD096266]
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [R21HD076347, R01HD096266] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK096266] Funding Source: NIH RePORTER
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Uterine glands are essential for pregnancy establishment. By employing forkhead box A2 (FOXA2)-deficient mouse models coupled with leukemia inhibitory factor (LIF) repletion, we reveal definitive roles of uterine glands in embryo implantation and stromal cell decidualization. Here we report that LIF from the uterine glands initiates embryo-uterine communication, leading to embryo attachment and stromal cell decidualization. Detailed histological and molecular analyses discovered that implantation crypt formation does not involve uterine glands, but removal of the luminal epithelium is delayed and subsequent decidualization fails in LIF-replaced glandless but not gland-containing FOXA2-deficient mice. Adverse ripple effects of those dysregulated events in the glandless uterus result in embryo resorption and pregnancy failure. These studies provide evidence that uterine glands synchronize embryo-endometrial interactions, coordinate on-time embryo implantation, and impact stromal cell decidualization, thereby ensuring embryo viability, placental growth, and pregnancy success.
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