Toxicity mechanism of peri-implantation pesticide beta-cypermethrin exposure on endometrial remodeling in early pregnant mice.

Beta-cypermethrin (ß-CYP) is a universally used pyrethroid pesticide with adverse effects on human health. ß-CYP may impair endometrial remodeling in mice; however, the mechanism remains largely unknown. Endometrial remodeling plays a vital role in embryonic development and the maintenance of pregnancy. Therefore, we explored the mechanism by which peri-implantation ß-CYP administration reduces uterine remodeling in pregnant mice. The C57BL/6 J pregnant mice were administered a dose of 20 mg/kg.bw. d ß-CYP via oral gavage once daily from day 1 of gestation (GD1) to GD7. Molecular markers of endometrial remodeling, stromal cell proliferation, cell cycle regulation, and the PI3K/Akt/mTOR signaling pathway were evaluated in the decidual tissue of the uterus on GD7. An in vivo pseudopregnancy mouse model, a pregnant mouse model treated with an mTOR activator and an mTOR inhibitor and an in vitro decidualization model of mouse endometrial stromal cells were used to confirm ß-CYP-induced defective endometrial remodeling and the key molecules expression of PI3K/Akt/mTOR signaling pathway. The results showed that ß-CYP decreased the expression of the endometrial remodeling markers MMP9 and LIF in the uterine decidua. Peri-implantation ß-CYP treatment markedly downregulated the expression of endometrial proliferation markers PCNA and Ki67 and decreased decidua thickness. Correspondingly, peri-implantation ß-CYP exposure upregulated the expression of FOXO1, P57 and p-4E-BP1 in the decidua. Further experiments showed ß-CYP significantly inhibited key molecules in the PI3K/Akt/mTOR pathway: PI3K, p-Akt/Akt, p-mTOR, and p-P70S6K in the uterine decidua. Additional experiments showed that aberrant endometrial remodeling induced by ß-CYP was aggravated by rapamycin (an mTOR inhibitor) and partially reversed by MHY1485 (an mTOR agonist). In summary, our results indicated that a reduction in the PI3K/Akt/mTOR pathway may enhance defective endometrial remodeling by downregulating the proliferation and differentiation of endometrial stromal cells in early pregnant mice exposed to ß-CYP. Our study elucidates the mechanism of defective endometrial remodeling induced by peri-implantation ß-CYP exposure.

Early pregnancy exposure to beta-cypermethrin compromises endometrial decidualisation in mice via downregulation of cyclin D3, CDK4/6, and p21.

Beta-cypermethrin (ß-CYP) is a highly effective broad-spectrum insecticide that can potentially affect female reproduction. However, little is known about the effect of ß-CYP on uterine decidualisation, which is a vital process by which the uterus provides a suitable microenvironment for pregnancy maintenance. Therefore, we focused on the effect and mechanism of ß-CYP on endometrial decidualisation during early pregnancy in mice. The results indicated that the expression levels of HOXA10, BMP2, and IGFBP1 was significantly downregulated in the decidual tissue and primary endometrial stromal cells of pregnant and pseudopregnant mice following ß-CYP treatment. Serum E2 concentration was significantly increased, whereas P4 concentration and oestrogen receptor (ERα) and progesterone receptor (PRA) expression were significantly downregulated following ß-CYP exposure. The number of polyploid decidual cells was lower in the ß-CYP-treated group. Furthermore, ß-CYP significantly downregulated the protein expression levels of CDK4 and CDK6, and the mRNA expression levels of cyclin D3 and p21. The number of foetuses per female in the first litter was markedly reduced following exposure to ß-CYP. In summary, early pregnancy exposure to ß-CYP may result in defective endometrial decidualisation via compromised proliferation of uterine stromal cells and reduced expressions of cyclin D3, CDK4/6, and p21 in mice.

Exposure to beta-cypermethrin impairs the reproductive function of female mice.

This study aimed to investigate the effects of beta-cypermethrin (ß-CYP) on female reproductive function and examine the morphology of the uterine endometrium and follicular development. The results found that the rate of successful pregnancy in the ß-CYP-treated groups significantly decreased. The levels of serum E2 and FSH were significantly increased in the ß-CYP-treated groups. The concentrations of serum P and LH were significantly decreased in the ß-CYP-treated groups. The uterine endometrium was damaged and the endometrial pinopode was markedly inhibited. In addition, the total number of follicles of all types was significantly lower in the medium- and high-dose ß-CYP-treated groups. These results suggest that ß-CYP significantly affected the reproductive function of female mice. ß-CYP may have significantly decreased the fertility of female mice by disturbing the reproductive hormone concentrations and inhibiting the development of the endometrium and the endometrial pinopode.

Effect of beta-cypermethrin exposure on embryo implantation in mice.

The aim of this study was to investigate the effect of ß-CP on embryo implantation in mice. Forty female mice were randomly assigned to four groups of 10 mice each: one control group and three ß-CP treated groups. The control group was administered corn oil only, while the three ß-CP-treated groups were given corn oil containing 5, 10, and 20 mg/kg bw d ß-CP for 3 months through intragastric administration. The results indicated that the administration of ß-CP decreased the rate of embryo implantation (all p < 0.05), E2 level in the serum, and the expression of Homeobox A10 (HoxA10) protein. In addition, ß-CP significantly increased ERa and PRA protein expression levels. These results suggest that ß-CP can disrupt the balance of E2 and P, influence ERa and PRA expression and their downstream-related molecule Hoxa10, and decrease embryo implantation.