Endometrial-trophoblast interactions in the regulation of placental invasion into the uterus

Trophoblast organoids with EVT differentiation

Primary Supervisor: Irving Aye (ia319@medschl.cam.ac.uk)

Second Supervisor: Naomi McGovern (nm390@cam.ac.uk)

Host Department or Institute: Department of Obstetrics & Gynaecology

Project description

Impaired placental trophoblast invasion into the endometrium is the underlying cause of the major pregnancy complications preeclampsia and fetal growth restriction (FGR), yet the regulatory mechanisms remain poorly understood. The project aims to elucidate the molecular mechanisms underlying maternal–fetal interactions that regulate trophoblast invasion during early placentation.

This project utilizes 2D and 3D co-culture models of human trophoblasts and endometrial cells developed in the supervisors’ labs to characterize: (i) paracrine signaling mediated by secreted factors and (ii) cell surface ligand–receptor interactions, regulating trophoblast invasion into endometrial stromal cells. Candidate receptors and ligands on each cell type (i.e. trophoblasts or endometrial cells) will be targeted (e.g. knockdown or overexpressed) and their role in regulating trophoblast invasion functionally examined. We will prioritise secreted factors previously found to be implicated in preeclampsia and/or fetal growth restriction (Ref #1). Investigation of the direct interactions between cell surface receptors and ligands will be based on ligand-receptor pairs predicted from spatial transcriptomics analyses (Ref #2).

Leveraging on the expertise of both supervisors’ labs, the candidate will receive training in trophoblast and endometrial biology, advanced cell culture techniques and computational biology. Examples of research techniques include (but not limited to):

  • Gene targeting using lentiviral mediated shRNA knockdown and Crispr/Cas9 knockout and overexpression.
  • Primary cultures of human trophoblast stem cells and endometrial stromal cells in 2D or 3D as monocultures or co-cultures.
  • Wet lab-based approaches for bulk RNA-sequencing, single cell RNA-sequencing, ChIP-seq/Cut and Run.
  • Bioinformatics analyses of the above sequencing data.

Additional information about the supervisors’ labs can be found below.

Dr Irving Aye

Dr Naomi McGovern

Candidate background

  • Undergraduate degree in biology or related field.
  • Wet lab research experience (e.g. summer projects, undergraduate or masters project) is essential.
  • Dry lab (computational) experience is desirable.

References

  1. Miao R*, Gong SS*, Sovio U*, Aye ILMH*, Avellino G, Guettler J, Rogers SN, Cook E, Toribio A, Bergman L, Lager S, Wikström AK, IMPACT consortium, Kirk PDW, Charnock-Jones DS*, Smith GCS*. Isthmin-2 is a first trimester predictor of preeclampsia and fetal growth restriction. Nature Medicine 2026; DOI: 10.1038/s41591-026-04573-6
  2. Aruntyunyan A, Roberts K, Troule K,….Vento-Tormo. Spatial multiomics map of trophoblast development in early pregnancy. Nature 2023; DOI: 10.1038/s41586-023-05869-0
  3. Yoshida N, Appios A, Li Q, Hutton JP, Wood G, Potts M, Aleksandrowicz J, Barrozo ER, Dover F, Anderson H, Stephens K, Aye ILMH, Thomas JR, Schenk HCM, Bourke AM, Aiken CE, Moffett A, Sharkey A, Protasio AV, Aargard KM, Edgar JR, Chung BYW, McGovern N. Interactions between placental Hofbauer cells and L. monocytogenes changes throughout gestation. Science Immunology. 2025; 10(109)eadq3066, DOI: 10.1126/sciimmunol.adq3066
  4. Aye ILMH, Tong S, Charnock-Jones DS, Smith GCS. The human placenta and its role in reproductive outcomes revisited. Physiological Reviews. 2025; DOI: 10.1152/physrev.00039.2024

  5. Li Q, Sharkey A, Sheridan M, Magistrati E, Aruthyunyan A, Huhn O, Sancho-Serra C, Anderson H, McGovern N, Esposito L, Fernando R, Gardner L, Vento-Tormo R, Turco MY, Moffett A. Human uterine natural killer cells regulate differentiation of extravillous trophoblasts early in pregnancy. Cell Stem Cell. 2024; 31(2):181-195.e9; DOI: 10.1016/j.stem.2023.12.013