Altered uterine leptin signalling in obese mothers: from impaired decidualisation to pregnancy complications.

IN BRIEF

Maternal obesity impairs uterine function, compromising embryo implantation and pregnancy establishment, posing also long-term risks to offspring health. We explore the contribution of impaired decidualisation to failed embryo implantation and placentation in obese mothers, highlighting the role of altered uterine leptin signalling in the dysregulation of extracellular matrix remodelling, vascularisation and cell proliferation and differentiation.

ABSTRACT

Obesity drastically affects maternal health and reproductive outcomes, being often associated with endocrine imbalance, compromised ovarian function and pregnancy complications. The plastic nature of pregnancy may render the developing foetus particularly vulnerable to oscillations in maternal metabolism, ultimately shaping the health trajectories of the offspring. Presently, we discuss the effect of maternal obesity on decidualisation, a critical step for embryo implantation and placental development. Decidualisation encompasses the differentiation of endometrial stromal cells into specialised decidua. Impaired decidualisation was linked to pregnancy complications, and recent studies suggest that maternal obesity has a detrimental effect on decidualisation. Leptin, an adipokine significantly increased in the circulation of obese women, is known to regulate endometrial function and decidualisation, modulating immune response, angiogenesis and cell proliferation. Furthermore, hyperleptinaemia in obese mothers was linked to altered leptin signalling in the uterus and compromised endometrial function. In this review, we explore the underlying molecular mechanisms linking altered uterine leptin signalling to impaired decidualisation and early pregnancy complications in obese mothers.