Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: A hypoxia-induced Rab pathway regulates embryo implantation by controlled trafficking of secretory granules.

Authors: Bhurke, Arpita; Kannan, Athilakshmi; Neff, Alison; Ma, Qiuyan; Laws, Mary J; Taylor, Robert N; Bagchi, Milan K; Bagchi, Indrani C

Published In Proc Natl Acad Sci U S A, (2020 06 23)

Abstract: Implantation is initiated when an embryo attaches to the uterine luminal epithelium and subsequently penetrates into the underlying stroma to firmly embed in the endometrium. These events are followed by the formation of an extensive vascular network in the stroma that supports embryonic growth and ensures successful implantation. Interestingly, in many mammalian species, these processes of early pregnancy occur in a hypoxic environment. However, the mechanisms underlying maternal adaptation to hypoxia during early pregnancy remain unclear. In this study, using a knockout mouse model, we show that the transcription factor hypoxia-inducible factor 2 alpha (Hif2α), which is induced in subluminal stromal cells at the time of implantation, plays a crucial role during early pregnancy. Indeed, when preimplantation endometrial stromal cells are exposed to hypoxic conditions in vitro, we observed a striking enhancement in HIF2α expression. Further studies revealed that HIF2α regulates the expression of several metabolic and protein trafficking factors, including RAB27B, at the onset of implantation. RAB27B is a member of the Rab family of GTPases that allows controlled release of secretory granules. These granules are involved in trafficking MMP-9 from the stroma to the epithelium to promote luminal epithelial remodeling during embryo invasion. As pregnancy progresses, the HIF2α-RAB27B pathway additionally mediates crosstalk between stromal and endothelial cells via VEGF granules, developing the vascular network critical for establishing pregnancy. Collectively, our study provides insights into the intercellular communication mechanisms that operate during adaptation to hypoxia, which is essential for embryo implantation and establishment of pregnancy.

PubMed ID: 32513733 Exiting the NIEHS site

MeSH Terms: Animals; Basic Helix-Loop-Helix Transcription Factors/genetics; Basic Helix-Loop-Helix Transcription Factors/metabolism*; Cell Communication/physiology; Cell Hypoxia/physiology*; Cell Line; Embryo Implantation/physiology*; Embryo, Mammalian; Endometrium/cytology; Endometrium/metabolism; Female; Gene Knock-In Techniques; Humans; Male; Mice; Mice, Knockout; Pregnancy; RNA Interference; RNA, Small Interfering/metabolism; Secretory Vesicles/metabolism*; Signal Transduction/physiology; Stromal Cells; rab GTP-Binding Proteins/genetics; rab GTP-Binding Proteins/metabolism*

Back
to Top