Placental autophagy in maternal obesity and gestational diabetes mellitus

Obesity is exponentially increasing worldwide, especially in women of reproductive age. Maternal obesity (MO)
during pregnancy represents a significant risk for both the mother and the fetus, with short and long-term health
consequences. The most prevalent maternal complication is Gestational Diabetes Mellitus (GDM), affecting almost
50% of obese pregnant women. Offspring of obese and/or GDM mothers is at higher risk to develop metabolic and
cardiovascular diseases during infancy and also later in adulthood. The placenta plays a key role during pregnancy,
ensuring appropriate maternal-fetal crosstalk and exchange of nutrients, gases, hormones and waste products. MO
and GDM, which are characterized by systemic low-grade inflammation, hyperglycemia and lipotoxicity, are known to
impact the intrauterine environment and the placenta, possibly leading to placental dysfunction. Indeed, alterations of
placental structure, nutrient transport, mitochondrial features and other placental functions have been reported in MO
and GDM. Autophagy is a lysosome-dependent mechanism consisting in the degradation of superfluous or damaged
cellular components, including macromolecules (e.g. proteins, lipids) and organelles (e.g. mitochondria, ribosomes)
to maintain cell homeostasis. Currently, the importance of autophagy is emerging in mammalian pregnancy, also in
the context of MO and GDM. Increasing evidences from murine models showed that autophagy appears to sustain
the gestation in many phases, such as zygote formation, blastocyst implantation and placentation. Few studies have
reported preliminary data focusing on autophagy in human placentas, highlighting that placental autophagy needs to
be a finely regulated process in order to ensure the balanced homeostasis of this unique organ.