Implantation and Placental Development

Implantation and Placental Development Research Group

Research Group Head

pipette1The uterus must remodel substantially to provide “fertile soil” for the embryo to implant and grow. We investigate the mechanisms that enable the uterus to prepare for embryo implantation. Normal placental development is vital to support the embryo and regulate maternal systems during pregnancy. We are working to understand how a healthy placenta is developed and the role of abnormal placentation in the development of pregnancy disorders.

Our group is studying the molecular mechanisms governing the fundamental cell biology during uterine remodelling for embryo implantation. This work has direct translational relevance, particularly for patients with uterine infertility and implantation failure in IVF treatment. Conversely, preventing uterine preparation for implantation is an attractive strategy for non-hormonal contraception. Furthermore, many uterine remodelling aspects of implantation are shared in cancer progression.

We aim to improve maternal and fetal health outcomes through improved understanding and management of placental development and pregnancy diseases such as pre-eclampsia, intrauterine growth, and miscarriage. We are particularly interested in a group of serine proteases, the HtrA protease family, in placental development and pregnancy diseases. One of our major goals is to develop strategies for early detection and treatment of pre-eclampsia, a life-threatening disorder of human pregnancy. In addition, we are interested in the long-term health consequences of placental insufficiency and pregnancy diseases.

We utilise a number of strategies including molecular biology, biochemistry, cell culture, gene knockdown cell and knockout mouse models, and proteomics. We collaborate closely with specialist clinicians, and a particular emphasis of our research is to translate our basic research discoveries into clinically useful practices.

Research Projects

Research Group

Selected publications

  • Chen Q, Wang Y, Zhao M, Hyett J, Costa FS, Nie G (2016) Serum levels of GDF15 are reduced in preeclampsia and the reduction is more profound in late-onset than early-onset cases. Cytokine 83:226-230.

  • Heng S, Vollenhoven B, Rombauts LJ, Nie G (2015) A High-Throughput Assay for the Detection of α-Dystroglycan N-Terminus in Human Uterine Fluid to Determine Uterine Receptivity. J Biomol Screen 21(4):408-13.

  • Heng S, Paule SG, Li Y, Rombauts LJ, Vollenhoven B, Salamonsen LA, Nie G (2015) Post-translational removal of alpha-dystroglycan N-terminus by PC5/6 cleavage is important for uterine preparation for embryo implantation in women. FASEB 29:4011-4022.

  • Teoh SS, Zhao M, Wang Y, Chen Q, Nie G (2015) Serum HtrA1 is differentially regulated between early-onset and late-onset preeclampsia. Placenta 36:990-995.

  • Singh H, Zhao M, Chen Qi, Wang Y, Li Y, Kaitu’u-Lino TJ, Tong S, Nie G (2015) Human HtrA4 expression is restricted to the placenta, is significantly up-regulated in early-onset preeclampsia, and high levels of HtrA4 cause endothelial dysfunction. JCEM 100:E936-E945.

  • Paule S, Nebl T, Webb AL, Vollenhoven B, Rombauts LJF, Nie G (2015) Proprotein convertase 5/6 cleaves platelet derived growth factor A in the human endometrium in preparation for embryo implantation. Mol Hum Reprod 21:262-270.

  • Heng S, DynonK,Li Y, Edgell T, Rombauts LJ; Vollenhoven B, Nie G (2015) Development of a high throughput assay for human proprotein convertase 5/6 for detecting uterine receptivity. Anal Biochem 475:14-21.

  • Singh H, Nero TL, Wang Y, Parker MW, Nie G (2014) Activity-modulating monoclonal antibodies to the human serine protease HtrA3 provide novel insights into regulating HtrA proteolytic activities. PLoS ONE 7(9):e45956.

  • Ho H, Li Y, Nie G (2014) Inhibition of embryo implantation in mice through vaginal administration of a proprotein convertase 6 inhibitor. Reproductive Biology 14:155-159.

  • Singh H, Li Y, Fuller PJ, Harrison C, Rao J, Stephens AN, Nie G (2013) HtrA3 is downregulated in cancer cell lines and significantly reduced in primary serous and granulosa cell ovarian tumors. J Cancer 4:152-164.