Evaluation of vascular endothelial growth factor A and leukemia inhibitory factor expressions at the time of implantation in diabetic rats following treatment with Metformin and Pioglitazone

Abstract

Background: Implantation requires intimate crosstalk between the embryo and uterus for a successful establishment of pregnancy. Type 2 diabetes mellitus may lead to implantation failure. The effect of diabetes and its therapeutic drugs on implantation is still largely unclear.
 Objective: To assess the endometrial expression changes of vascular endothelial growth factor A (VEGFA) and leukemia inhibitory factor (LIF), at the time of implantation in diabetic rats following treatment with Metformin and Pioglitazone.
 Materials and Methods: Twenty-eight 6-8-wk-old Wistar female rats weighing 200- 250 gr were divided into four groups (n = 7/each). Type 2 diabetes was induced and Metformin and Pioglitazone were applied for 4 wk. The expression of VEGFA and LIF was measured by real-time reverse transcription-polymerase chain reaction and Western blot.
 Results: The relative expression of VEGFA transcript was higher in the diabetic (p = 0.02) and Metformin-treated (p = 0.04) rats compared to the control group. Furthermore, the VEGFA transcript level significantly reduced in Pioglitazone-treated diabetic rats (p = 0.03). LIF expression was elevated in the Metformin- and the Pioglitazone-treated rats and reduced in the diabetic group in comparison with the control group. Compared to the diabetic rats, the expression of LIF was significantly elevated in the Metformin- (p = 0.01) and Pioglitazone-treated (p = 0.03) groups.
 Conclusion: The expressions of LIF and VEGFA were altered in diabetic rats during implantation which may be associated with diabetic-related infertility. Pioglitazone is able to restore the VEGFA and LIF expressions to their baseline levels more efficiently than Metformin.
 Key words: Embryo implantation, Leukemia inhibitory factor, Vascular endothelial growth factor A, Metformin, Pioglitazone, Rats.

The Role of Pioglitazone Against Ehrlich Solid Carcinoma Mice Model Through Antiproliferative and Antiangiogenic Pathways

“…Also, Zarei et al showed a reduced expression of VEGF in mice treated with pioglitazone. Consequently, the present results revealed a better antiproliferative effect when Pio is added to the standard chemotherapeutic treatment (Zarei et al, 2020).…”

“…These results were in the same line with Ni and collegues, who showed the interplay between troglitazone and chemotherapeutic drugs Cis or paclitaxel' in xenotransplantation models indicating the chemotherapeutic drugs induction of PPAR-γ (Ni et al, 2017), in addition to the reported sequence-specific synergy between PPAR-γ ligands and chemotherapeutic agents in the treatment of cancer. Recent evidence shows that PPAR-agonists could serve as master modulators in the battle against cancer therapy's classic challenges, such as resistance to treatment and tumor genetic heterogeneity (Heudobler et al, 2018, Yousefnia et al, 2018, Zarei et al, 2020. Furthermore, p-AMPK/ ERK ½ signaling pathways were inhibited by reduced p-AMPK, ERK1, and ERK2 in mice treated with the Cis+(Pio HD) group.…”

Secretomes from Conventional Insemination and Intra-Cytoplasmic Sperm Injection Derived Embryos Differentially Modulate Endometrial Cells In Vitro

“…MUC-1, also receptivity marker, regulates implantation by inhibiting cell-to-cell adhesion. Local reduction of MUC-1 expression at attachment sites allows the blastocyst to implant and, MUC-1 expression is reported to be critical for the selection of high-quality embryos [ 43 ]. It was envisaged a comparison of the ability of secreted factors from CI- and ICSI- derived embryos to modify the endometrial epithelial cells will indirectly establish whether the molecular profiles of that CI- and ICSI- derived embryos are similar or dissimilar.…”