Miscarriage, also termed spontaneous abortion, is one of the most frequent complications during gestation, and approximately 80% of all miscarriages occur in the first trimester. Miscarriage affects 10%–15% of pregnant women [1]. The etiology of miscarriage is extraordinarily intricate, and chromosomal abnormalities in the fetus are the major causative factor [2], accounting for nearly 50%–60% of all early miscarriages [3]. Other causative factors, such as endocrine disorders, congenital abnormal uterine anatomy, immune system disease, thrombophilia, and infections also induce miscarriage [[4], [5], [6], [7]]. For the past few years, increasing studies have reported that some metabolic processes, such as glucose and lipid metabolism, play an important role in the occurrence and development of miscarriage [8,9].

Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) is a nuclear receptor-assisted activator [10], that works together with the nuclear receptor PPAR-γ to enhance cell oxidative phosphorylation (OXPHOS) and mitochondrial biogenesis [11]. PGC-1α is mainly found in the mitochondria and has high energy requirements related to the functioning of several tissues, including the heart [12], skeletal muscle [13] and placenta [14]. Our previous study found that OXPHOS was significantly enhanced in trophoblast cells of miscarriage owing to disturbed cell metabolic reprogramming [9]. Moreover, the cell cycle genes were decreased in the miscarriage placenta. However, the exact causes underlying the mechanisms of unexplained miscarriage remain unknown.

In the present study, we found that PGC-1α expression was dramatically increased in miscarriage chorionic villous tissue. Given that PGC-1α plays a significant role in metabolic regulation, it was hypothesized that PGC-1α upregulation affected trophoblast metabolism and may be associated with the occurrence and progression of miscarriage. Our biological experiments demonstrated that PGC-1α dysregulation induced metabolic disorders, which presented as increased reactive oxygen species (ROS) level, reduced mitochondrial membrane potential, and reduced NADPH synthesis. These disorders blocked cell proliferation and elevated cell apoptosis. Thus, these results provided a new insight into the mechanism of early miscarriage.