Mechanisms underlying fetal intrauterine growth restriction and placental injury induced by preconception co-exposure to β-cypermethrin and emamectin benzoate in rats
- VernacularTitle:孕前高效氯氰菊酯与甲维盐联合暴露致大鼠胎仔宫内生长受限及胎盘损伤机制
- Author:
Wenxin BAI
1
;
Xianzhi HE
2
;
Yuqing QIU
1
;
Yuxin LI
3
;
Bin SUN
4
;
Yuanyuan LI
5
;
Qingfeng ZHAI
1
Author Information
- Publication Type:Selectedarticle
- Keywords: beta-cypermethrin; emamectin benzoate; fetal intrauterine growth restriction; placenta; mitophagy
- From: Journal of Environmental and Occupational Medicine 2026;43(9):1086-1095
- CountryChina
- Language:Chinese
- Abstract: Background Intrauterine growth restriction (IUGR) is closely associated with placental dysfunction. However, the effects of preconception co-exposure to β-cypermethrin (β-CYP) and emamectin benzoate (EMB) on fetal growth and placental function remain unclear. Objective To investigate the effects of prenatal exposure to β-CYP and EMB on embryonic development in female rats and to elucidate the mechanisms by which these substances cause IUGR from the perspectives of placental structure, progesterone synthesis, and mitochondrial autophagy. Methods Forty-eight specific pathogen-free (SPF) adult female Sprague-Dawley (SD) rats were randomly assigned to a control group, a β-CYP group, an EMB group, and a co-exposure group (n=12 per group). A whole-body dynamic inhalation exposure system was used to simulate greenhouse exposure. Rats in the control group were exposed to clean air, whereas those in the exposure groups were exposed to β-CYP (55 mg·m−3), EMB (7.8 mg·m−3), or their combination for 2 h per day for 90 consecutive days. After exposure, ovarian and serum estradiol (E2) levels were determined in six rats from each group, while the remaining six rats were mated. Of the mated rats, three per group were sacrificed on gestational day 18, and the other remaining three were allowed to deliver naturally. Pregnancy outcomes and fetal development were evaluated. Placental morphology, progesterone (Prog) levels, progesterone synthesis-related factors, oxidative stress, mitochondrial function, and mitophagy-related indicators were subsequently assessed. Results Compared with the control group, fetal body weight on gestational day 18 and neonatal body weight were significantly decreased, whereas the incidence of IUGR was significantly increased in the β-CYP, EMB, and co-exposure groups (P<0.05). The EMB and co-exposure groups exhibited an increased proportion of the placental junctional zone thickness to total placental thickness and a reduced proportion of the labyrinth zone (P<0.05). Ovarian E2 and placental Prog levels were decreased in all three exposure groups. In addition, the placental expression of cytochrome P450 family 11 subfamily A member1(CYP11A1)、3β-hydroxysteroid dehydrogenase type 1(HSD3B1)、progesterone receptor(PgR) was downregulated, catalase (CAT) activity and adenosine triphosphate (ATP) content were reduced, and lactate dehydrogenase (LDH) activity was increased in all exposure groups (P < 0.05). Furthermore, the expression of translocase of outer mitochondrial membrane 2 was decreased, whereas the expression levels of microtubule-associated protein 1 light chain 3 (LC3), PTEN-induced kinase 1 (PINK1), parkin RBR E3 ubiquitin-protein ligase (Parkin), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) were increased in all exposure groups (P<0.05). Conclusion Prenatal exposure to β-CYP and EMB can cause structural damage to the rat placenta, affect the expression of markers related to progesterone synthesis, and is accompanied by oxidative stress, mitochondrial dysfunction, and alterations in PINK1/Parkin-mediated mitochondrial autophagy, ultimately affecting the intrauterine growth and development of the fetus.
