The link between placental insufficiency, fetal growth restriction and adulthood overweight was revealed

Lead researcher

Professor, Guiying, Nie

Main finding

High temperature requirement factor A3 (HtrA3) is an enzyme that is highly produced in the developing placenta both in mice and women. It was originally discovered by Prof Nie’s team in 2003.

In the current study, the team deleted HtrA3 in mice and investigated placental development and function. It was discovered that the maternal rather than fetal HtrA3 is critically important for optimal placental development – deletion of HtrA3 in the mother resulted in placental insufficiency and intra-uterine growth restriction (IUGR).

The IUGR caused by maternal HtrA3 deletion, albeit being mild, significantly altered offspring growth trajectory long after birth. By 8 months of age, mice born to HtrA3-deficient mothers, independent of their own genotype, were significantly heavier and contained a larger mass of white fat.

The study also also demonstrated an association between lower HtrA3 and placental insufficiency in the human.


Centre for Reproductive Health

Research group

Implantation and Placental Development


Ms, Ying, Li
Prof, Lois, Salamonsen,
Prof, Jonathan, Hyett
A/Prof, Fabricio da Silver, Costa
Prof, Guiying, Nie

Journal and article title

Most surprising

The impact of placental insufficiency during pregnancy is long-lasting – it not only affects fetal growth in utero but also adversely influences the offspring growth and heath long after birth.

Future implications

This study presents a scenario where adulthood overweight arises from subtle growth restriction in utero rather than an individual’s genetic composition, environmental insults or food access. It strongly supports the emerging theory of the in utero origins of obesity, and has important implications in the understanding of the current obesity epidemic.

Disease/health impact

Overweight and obesity