Sex and Circadian Timing Modulate Oxaliplatin Hematological and Hematopoietic Toxicities.

Oxaliplatin was nearly twice as hematotoxic, with optimal circadian timing differing by 6 h, in women as compared to men with colorectal cancers. Hence, we investigated sex- and timing-related determinants of oxaliplatin hematopoietic toxicities in mice. Body-weight loss (BWL), blood cell counts, bone marrow cellularity (BMC) and seven flow-cytometry-monitored hematopoietic progenitor populations were evaluated 72 h after oxaliplatin chronotherapy administration (5 mg/kg). In control animals, circadian rhythms of circulating white blood cells showed a peak at ZT5 in both sexes, whereas BMC was maximum at ZT20 in males and ZT13h40 in females. All BM progenitor counts presented robust rhythms with phases around ZT3h30 in females, whereas only three of them rhythmically cycled in males with a ≈ -6 h phase shift. In treated females, chronotoxicity rhythms occurred in BWL, WBC, BMC and all BM progenitors with the best timing at ZT15, ZT21, ZT15h15 and ZT14h45, respectively. In males, almost no endpoints showed circadian rhythms, BWL and WBC toxicity being minimal, albeit with a substantial drop in BM progenitors. Increasing dose (10 mg/kg) in males induced circadian rhythms in BWL and WBC but not in BM endpoints. Our results suggest complex and sex-specific clock-controlled regulation of the hematopoietic system and its response to oxaliplatin.

Improving maternal welfare during gestation has positive outcomes on neonatal survival and modulates offspring immune response in pigs.

Improving the housing of pregnant sows by giving them more space and access to deep straw had positive effects on their welfare, influenced their maternal behavior and improved the survival of their offspring. The present study aimed at determining whether these effects were actually due to environmental enrichment and whether the provision of straw pellets and wood can partly mimic the effects of straw bedding during gestation. Three graded levels of enrichment were used, that were, collective conventional pens on slatted floor (C, n = 26), the same pens with manipulable wood materials and distribution of straw pellets after the meals (CE, n = 30), and larger pens on deep straw litter (E, n = 27). Sows were then housed in identical farrowing crates from 105 days of gestation until weaning. Decreased stereotypies, blood neutrophils, and salivary cortisol, and increased behavioral investigation indicated that health and welfare of sows during gestation were improved in the E environment compared with the C environment. The CE sows responded as C or E sows depending on the trait. Piglet mortality rate in the first 12 h after birth was lower in E and CE litters than in C litters, but enrichment level during gestation had only small effects on lactating sow behavior and milk composition postpartum. On days 2 and 3 of lactation, E sows interrupted less often their nursing sequences than C and CE sows. On day 2, milk from both E and CE sows contained more minerals than that from C sows. In one-day-old piglets, the expression levels of genes encoding toll-like receptors (TLR2, TLR4) and cytokines (interleukin-1, -6 and -10) in whole blood after 20-h culture, were greater in E piglets than in CE or C piglets. In conclusion, housing sows in an enriched environment during gestation improved early neonatal survival, probably via moderate and cumulative positive effects on sow behavior, milk composition, and offspring innate immune response. The gradation in the effects observed in C, CE and E housing environment reinforced the hypothesis of a causal relationship between maternal environmental enrichment, sow welfare and postnatal piglet traits.

Relationship between ranging behavior and spatial memory of free-range chickens.

Different personalities may lead to different ways of processing environmental information; however, the relationship between personality and cognition is not fully understood as studies on diverse species present contrasting results. As there is great within-flock variability of outdoor ranging behavior in free-range broiler chickens, we tested whether and how ranging behavior impacts on individual spatial memory abilities. The experiment was conducted on one flock (n = 200) reared in the same conditions throughout the study, to simulate on-farm situations. As the ranging behavior was stable over time, we compared two distinct groups of male chickens: one that visited the range more (High rangers) and one that was more prone to staying in the poultry house (Low rangers). To test the spatial memory, individuals (n = 30) went through two main phases in an arena with 8 cups. For the familiarization phase, individuals were submitted to one trial per day, for seven days, to a situation where all eight cups were baited with mealworms. Animals had to reach a criterion of 5 cups visited out of 8 to advance to the next phase. For the spatial test, only four cups were baited and systematically placed at the same location. This last phase comprised two trials per individual per day, for nine days. During these two phases, latency to visit cups and the number of visits and revisits of all cups were recorded. Low ranger chickens took less time to attain the pre-established threshold of visiting 5 cups out of 8, over the familiarization phase. During the spatial test, the latency to visit four cups decreased between the within-day trials for low ranger chickens and increased for high ranger chickens. Moreover, in the within-day trial analysis, low ranger chickens exhibited an improvement on spatial memory and better spatial memory compared to high ranger chickens. Different speed-accuracy trade-offs may explain these differences between low and high ranger chickens and the way individuals interact and solve the task. Our study strengthens the scientific evidence relating consistent individual differences in behavior, with the ranging behavior of free-range chickens, and cognitive performance during a spatial memory task.