Toxic Effects Of Isocarbophos On The Reproductive Function, Pathology Of Male Rats And The Growth Of Offspring

Isocarbophos is a new type of efficient organic phosphorus pesticides. Toxicity studies of isocarbophos at home and abroad are only a small number of acute poisoning, delayed neuropathy and toxic effects of biofilm research reports [1,2] and its impact on male reproductive function is reported rarely. In this study, male rats were fed with isocarbophos. The reproductive function and pathology of male rats, the growth and development of offspring were observed in order to provide a scientific basis to further understand the toxicity of isocarbophos. In addition, this experiment also observed pathology of hypothalamus-pituitary-gonadal axis on male rat, in order to explore new ideas of the possible mechanisms that isocarbophos affect male reproductive function.A total of 120 rats (female: 80, male:40) was randomly divided into four groups: control group(0 mg/kg), low-dose group(0.3 mg/kg), media-dose group(3 mg/kg), high-dose group(6 mg/kg). Rats were exposed to isocarbophos by food mixed with dissolved isocarbophos. After 8-week treatment, male and female rats were mated in rate of 2∶1. Sperm was determined by the method of sperm smear in everyday morning. The day that sperm was found was recorded as the 0 day of pregnancy. The pregnant rat was fed in single cage. The weight, length, tail length and chest circumference of offspring were measured at 0, 4, 7, 14, and 21 days. After mated, male rats were killed. The hypothalamus, pituitary, testis, epididymis, prostate and seminal vesicle were removed, weighed and calculated the organ coefficient; HE staining and electron microscopy were used to observed pathological changes; the content of calcium, magnesium, copper, zinc in testicular tissue were determined by the method of atomic absorption spectrometry; sperm in tail of epididymis were collected and counted; the activity rate and the abnormal rate of sperm were calculated. The experiment discussed effects of isocarbophos on structure and function of reproduction system from a number of aspects.The results showed that: 1 The body weight and organ coefficient of male rats were not affected by iscarbophos significantly (P>0.05). 2 HE staining (1) Hypothalamic neurons edema can be observed in high dose group. (2)Eosinophil in adenohypophysis increased with the dose increasing. (3) In the groups treated by isocarbophos, the counts and layers of spermatogenic cells obviously decreased with the dose increasing. The pathological changes of epididymis, prostate and seminal vesicle were not observed. 3 Electron microscopy (1) Swelling of mitochondria in hypothalamic neurons increased with the dose increasing, edema of neuron can be observed in high-dose group; glial cells had no obvious structural changes. (2) nuclear-week gap wide, the expansion of the endoplasmic reticulum and mitochondrial swelling in a dose-dependent increase in growth hormone cells; with increasing dose, mitochondrial swelling in gonadotropin cells gradually increased; adrenocorticotropic hormone cells, thyroid-stimulating hormone cells and prolactin cells had no obvious structural changes. (3) Edema of Sertoli cells were observed in middle and high group; edema of spermatogonia aggravated with the dose increaseing, spermatogonium necrosis and destruction of membrane structure can be observed in high-dose-group; loss of dense fiber can be observed in middle-and high-dose group; spermatocytes and sperm cells had no significant structural changes in each dose group. 4 The contents of calcium and copper increased with the dose increasing. The content of copper obviously increased in the middle-and high-dose group, contrast with the control group (P<0.05). On the contrary, the contents of magnesium and zinc decreased with the dose increasing. The contents of magnesium and zinc in high dose group were lower than that in the control group (P<0.05). 5 Sperm count and the rate of sperm activity in treated groups were decreased obviously, contrast with the control group (P<0.01 and P<0.05). The rate of sperm deformity was higher than the control group, the difference was significant statistically (P<0.01 and P<0.05). 6 The rate of success mating and birth rate in high-dose group were lower than the control group (P<0.05). 7 The weight, length, tail length, chest circumference of offspring decreased in treated groups, contrast with the control group (P<0.05, P<0.01 or P<0.001).The above results clearly indicated that isocarbophos can directly lead to the harm of testicular tissue, decreasion of the counts and layers of spermatoogenic cells, pathological changs of spermatogonia, Sertoli cells and sperm. The damage of testicular tissue resulted in sperm count and the rate of sperm activity decreasing, the rate of sperm abnormality increaseing, thus isocarbophos affected the quality of sperm. Isocarbophos can interfere with sperm production, development and maturity through affecting the contents of calcium, magnesium, copper and zinc in testicular tissue, ultimately affect the breeding capacity of rats and the quality of offspring. In addition, isocarbophos can lead to pathological structural changes of hypothalamus-pituitary-testicular axis, indicated one possible mechanism of isocarbophos affecting reproductive function is that abnormal hormone secretion.