Adiponectin Reduces Embryonic Loss Rate and Ameliorates Trophoblast Apoptosis in Early Pregnancy of Mice with Polycystic Ovary Syndrome by Affecting the AMPK/PI3K/Akt/FoxO3a Signaling Pathway

Abstract

Reports in recent years have suggested that adiponectin (APN) improves insulin resistance and inhibits apoptosis by activating the AMP-activated protein kinase (AMPK) pathway and the PI3K/Akt signaling pathway after binding to its receptor. This study aims to explore the mechanism by which APN reduces embryo loss rate and trophoblast apoptosis in early pregnancy of mice with polycystic ovary syndrome (PCOS). PCOS mice were subcutaneously injected with APN (10 μg mg kg−1 day−1) on 11 consecutive days from the 3rd day of pregnancy onwards to observe the change of the embryo loss rate of PCOS mice induced by APN. Quantitative real-time PCR and Western blot were used to determine the relative expressions of mRNA and the proteins AMPK, PI3K, and Akt in mouse uterine tissue. At the same time, primary cultured mouse villous trophoblast cells were used to further explore the underlying mechanisms in vitro. APN significantly reduces the pregnancy loss rate of PCOS mice. At the same time, APN increases phosphorylation and mRNA expression levels of AMPK, PI3K, and Akt in PCOS mouse uterine tissue. In addition, trophoblast cells of model mice were treated with APN and inhibitors, and APN was found to reduce trophoblast cell apoptosis by affecting the phosphorylation levels of AMPK, PI3K, Akt, and FoxO3a proteins. APN reduces the embryo loss rate and ameliorates trophoblast apoptosis in PCOS mice by affecting the AMPK/PI3K/AKT/FoxO3a signaling pathway.

FPR2 serves a role in recurrent spontaneous abortion by regulating trophoblast function via the PI3K/AKT signaling pathway

“…The results of the present study demonstrated that FPR2 knockdown caused the phosphorylation of AKT and PI3K. AKT is the direct target protein of the PI3K signaling pathway and is associated with cell proliferation, differentiation, apoptosis and migration (44)(45)(46). Functional analyses in the present study revealed that FPR2 may be involved in the regulation of trophoblast function through the PI3K/AKT signaling pathway.…”

Energy sensors and reproductive hypothalamo-pituitary ovarian axis (HPO) in female mammals: Role of mTOR (mammalian target of rapamycin), AMPK (AMP-activated protein kinase) and SIRT1 (Sirtuin 1)

“…In KGN human granulosa cells, AMPK signaling pathways is activated in response to berberine that is known to improve insulin sensitivity and ovulation function in PCOS patients (Li, et al 2020). Recently, Zhang et al showed that AMPK pathway is involved in the reduction of the embryo loss rate in response to adiponectin treatment in PCOS mice (Zhang, et al 2020). In the well-established DHEA-induced PCOS mouse model, expression of SIRT1 and activation of AMPK are largely enhanced in ovary suggesting that SIRT1 through AMPK activation could modulate autophagy in PCOS ovaries (Di Emidio, et al 2020).…”

Therapeutic exploration of polyherbal formulation against letrozole induced PCOS rats: A mechanistic approach

“…The treatment of polyherbal syrup significantly improves the mRNA expression of AMPK and GLUT4 in the CHO cell line. The polyherbal syrup-activated AMPK expression in ovarian cells indicates that it can have the capacity to improve insulin resistance and regulate menstruation and promote ovulation by activating AMPK/PI3K/AKT/FoxO3 signaling pathway [ 51 , 52 ]. Also, the activation of AMPK down-regulates gluconeogenesis gene expression.…”