Concurrent administration of diethylhexyl phthalate reduces the threshold dose at which bisphenol A disrupts blastocyst implantation and cadherins in mice

•We examined individual and combined administration of DEHP and BPA.•Both can impede implantation in fertilized females, but dose-response curves differ.•DEHP or BPA doses that are insufficient on their own have an effect in combination.•Uterine e-cadherin is disrupted in conjunction with implantation failure.•Cadherin-11 was disrupted in females that received BPA.

Many people are repeatedly exposed to both bisphenol A (BPA) and diethylhexyl phthalate (DEHP), but there has been little research concerning their effects in combination. Both can disrupt blastocyst implantation in inseminated females, albeit at high doses. We exposed mice on gestation days (GD) 1-4 to combinations of BPA and DEHP in doses below the threshold necessary to disrupt implantation on their own. On GD 6, there were fewer normally-developed implantation sites and more underdeveloped implantation sites in females given the combined subthreshold doses. Uterine epithelial cadherin (e-cadherin), a protein that assists in blastocyst adhesion to the uterine epithelium, was significantly reduced by these combined doses, but not by the individual doses. A similar trend was seen in integrin αvβ3, another uterine adhesion molecule. Cadherin-11 was disrupted by BPA but not DEHP. These data are consistent with competition of BPA and DEHP for conjugating enzymes.