Effects Of Maternal Cypermethrin Exposure During Lactation On Reproductive Development In Male Offspring

Pesticide is an important environmental chemical pollutant, and easy residues in food. Cypermethrin [(R,S)-α-cyano-3-phenoxybenzyl (1R,S)-cis,trans-3-(2,2- dichlorovinyl) -2,2-dimethyl-cyclopropane], a synthetic pyrethroid insecticide, has been used worldwide to control noxious insects in agriculture, forestry, households, horticulture and the public health. With the expanding use of cypermethrin, its toxicity in mammals is also increasingly concerned. The Reproductive Toxicity of cypermethrin on adult mice have been reported,However, Relatively few studies have investigated potentially adverse effects of maternal cypermethrin exposure during lactation on male reproduction and endocrine disruption. Studies have shown that maternal exposure to environmental pollutants during pregnancy and early postnatal can harm the reproductive development of male offspring. The present study aimed to investigate the effects and mechanisms of maternal cypermethrin exposure during lactation on steroidogenesis and spermatogenesis in male offspring.To investigate the effects and mechanisms of maternal cypermethrin exposure during lactation on reproductive development in male offspring, Twenty-one healthy pregnant mice were randomly divided into three groups. Maternal mice were orally administered with different doses of cypermethrin (0, 6.25 and 25 mg/kg/d, 10 ml/kg) dissolved in corn oil daily from postnatal day 1 (PND1) to PND21. Fifteen male pups were randomly selected from each group and killed at PND21 after exposure. Testes were weighed and testicular organ coefficients were calculated. Histopathological changes in testicular tissues were observed by HE stain. Serum testosterone (T) and estrogen (E2),testicular T were measured by radioimmunoassay (RIA). The mRNA level of StAR and T synthetic enzymes in testes were determined by RT-PCR. The expression of testicular StAR and T biosynthetic enzymes was determined by western blot. Leydig cells in testes were identified by immunohistochemistry. Testicular apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL). The remaining male pups were weaned at PND 21, and fed a normal diet to adulthood (PND 70). Sperm quality and fertility were evaluated in adult male offspring at PND70. Testes were weighed, histopathological changes in testicular tissues were observed by HE stain. Serum testosterone (T) and estrogen (E2),testicular T were measured by RIA. The mRNA level of StAR and T synthetic enzymes in testes were determined by RT-PCR. The expression of testicular StAR and T biosynthetic enzymes was determined by western blot. Leydig cells in testes were identified by immunohistochemistry. Testicular apoptosis was detected by TUNEL. Results showed testicular weight and organ coefficients at PND21 were significantly decreased in pups in cypermethrin-treated mice in a dose-dependent manner (P<0.05 or P<0.01). In addition, maternal cypermethrin exposure markedly decreased the layers of spermatogenic cells, increased the inside diameter of seminiferous tubules, and disturbed the array of spermatogenic cells in testes of pups at PND21. The expression of testicular P450scc at PND21 was downregulated in pups of 25mg/kg group as compared with controls. Correspondingly, Serum T was significantly decreased in pups of 25mg/kg group as compared with controls and 6.25mg/kg group (P<0.01 or P<0.05). Testicular T was significantly decreased in pups of 25mg/kg group as compared with controls (P<0.05). Interestingly, although the expression of testicular P450scc and level of serum and testicular T at adulthood had restored to control level, the histological changes were irreversible. Importantly, the number of epididymal spermatozoa in male offspring of 25mg/kg group was decreased as compared with controls (P<0.05).In summary, maternal cypermethrin exposure during lactation induces a lasting damage on testicular development and spermatogenesis, whereas cypermethrin-induced damage on steroidogenesis is reversible.