Arsenic-induced autophagic alterations and mitochondrial impairments in HPG-S axis of mature male mice offspring (F1-generation): A persistent toxicity study.

Arsenic (As) has been implicated in causing reproductive toxicity, but the precise cellular pathway through which the As toxicity in mature F1- male mice hypothalamic-pituitary- gonadal- sperm (HPG-S) axis is induced has not well been documented. Hence, parental mice were treated to As2O3 (0, 0.2, 2, and 20 ppm in deionized water) from five weeks before mating until weaning, and the male pups from weaning to maturity. Afterward, the markers of oxidative stress, mitochondrial impairment, and autophagy as fundamental mechanisms of cytotoxicity and organ injury were evaluated. Higher As2O3 doses (2 and 20 ppm) were a potent inducer of oxidative stress, mitochondrial dysfunction, and autophagy in HPG-S axis. Concomitant with a dose-dependent increase in the number of MDC-labeled autophagic vacuoles in the HPG axis, an adverse dose-dependent effect was observed on the mean body weight, litter size, organ coefficient, and spermatogenesis. Transmission electron microscopy also revealed more autophagosomes at high As2O3 dosage. Concomitant with a dose-dependent increment in gene expression of PI3K, Atg5, Atg12, as well as protein expression of Beclin1, LC3- I, II, P62 in HPG axis tissues and Atg12 in the pituitary; a dose-dependent decrease in mTOR gene expression was recorded in the HPG tissues of mature F1-males. These observations provide direct evidence that oxidative stress-induced mitochondrial impairments and autophagic cell death, through AMPK/TSC/mTOR and LC3 related pathways, are fundamental mechanisms for As2O3- induced toxicity on the reproductive system in mature male mice offspring.

Reproductive performance of Holstein dairy cows in Iran.

The objectives of the present study were to describe the current reproductive parameters of Holstein dairy cows in Iran and to determine factors which have a significant effect on reproductive performance with emphasis on high-producing dairy cows. Five large Holstein dairy herds from the major milk production areas of Iran were selected for this study. Reproduction data including parity of dam, calving date, days to first service, days open, number of services, dry period, and occurrence of diseases for cows that calved from 2004 to 2007 were collected from the herds' databases. To determine the effects of year and season of calving, disease status, level of milk production, and parity of dam on reproductive parameters, the proc-mixed procedure in SAS software was used. Overall, data about 8,204 lactation were collected for the study. Results showed that mean (+/-SD) days open, calving interval, and days to first service for study herds were 134 (+/-89), 403 (+/-86), and 67 (+/-38) days, respectively. Conception rates at the first service and the overall service-conception rate were 41.6% and 41%, respectively. The level of milk production and diseases had significant negative effects on days open and service per conception (P < 0.05); statistical analysis showed that for every 100-kg increase in milk yield, days open will increase by about 0.3 days. However, no significant effect of level of productivity was observed on days to first service. The results of this study indicate that high milk production is a risk factor for decreasing fertility in Iran, like many other parts of the world.