Association between uterine toxicity induced by chlorpyrifos and downregulation of heparin-binding epidermal growth factor and L-selectin genes.

Various factors are effective in reducing the fertility rate. This experiment aimed to investigate chlorpyrifos (CPF), an organophosphate, that could alter the structure of the uterus and the molecules involved in parental and fetal. CPF was injected intraperitoneally in thirty mice for five days in a week (six weeks). The animals were euthanized on the 5th day of gestation, then their blood and uterus were collected for biochemical and histopathological assays. Exposure to CPF resulted in a significant reduction in maternal weight gain and the number of litters. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were significantly increased in blood serum of the CPF group compared with the control. The number of uterus glands, endometrium thickness, and the uterine cavity were changed following CPF injection. Additional investigation indicated that the expressions of L-selectin, L-selectin ligand, and heparin-binding epidermal growth factor (HB-EGF) as initial adhesion of mice blastocysts and maternal endometrium biomarkers were downregulated in the CPF group. Nevertheless, any mortality and abnormal clinical symptoms were not observed in the treated mice. This study revealed a potential molecular mechanism of continuous CPF-induced toxicity in fetal-maternal attachment without clinical symptoms.

Chlorpyrifos effects on integrin alpha v and beta 3 in implantation window phase.

Chlorpyrifos (CPF), as a worldwide pesticide, can effect on the integrins αv and ß3 which play a main role in the implantation window. Therefore, the aim of this study was to consider CPF effects on integrin alpha v and beta 3 in implantation window phase. Thirty female NMRI mice were separated into groups of CPF, sham, and control. After 6 weeks, each group was mated, and on the 5th day of gestation, all mice were euthanized. Estradiol and progesterone levels were detected by the enzyme-linked immunosorbent assay (ELISA) test; two subunits of integrins (αv and ß3) genes and proteins of endometrium were analyzed by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry method, respectively. Fibrosis of the liver which evaluated by Masson's trichrome stain was increased in the CPF group compared with the others. But estradiol and progesterone levels were significantly decreased in CPF groups. Based on the findings, the proportion of genes' expressions of integrin subunits declined by the effect of CPF, while there was not any notable consequence on mice in the sham group. Alpha v and beta 3 integrin proteins expressed in all groups, but the concentration of these proteins in CPF groups was lower than in other groups. This study has shown that the decline of estradiol and progesterone downregulates the expression of αv and ß3 integrins which were influenced by CPF exposure. Changing these patterns of proteins could have numerous influences on unsuccessful implantation. Therefore, this experimental study recommends that inclusive consideration of the effects of insecticides may be crucial to women's unrecognized cause of infertility.