Effect of circadian system disruption on the concentration and daily oscillations of cortisol, progesterone, melatonin, serotonin, growth hormone, and core body temperature in periparturient dairy cattle.

Metabolic, circadian, sleep, and reproductive systems are integrated and reciprocally regulated, but the understanding of the mechanism is limited. To study this integrated regulation, the circadian timing system was disrupted by exposing late pregnant nonlactating (dry) cows to chronic shifts in the light-dark phase, and rhythms of body temperature and circulating cortisol (CORT), progesterone (P4), serotonin (5HT), melatonin (MEL), and growth hormone (GH) concentrations were measured. Specifically, across 2 identical studies (1 and 2), at 35 d before expected calving (BEC) multiparous cows were assigned to control (CON; n = 24) and exposed to 16 h light and 8 h dark or phase shift (PS; n = 24) treatments and exposed to 6-h light-dark phase shifts every 3 d until parturition. All cows were exposed to control lighting after calving. Blood samples were collected in the first study at 0600 h on d 35 BEC, d 21 BEC, and 2 d before calving, and d 0, 2, 9, 15, and 22 postpartum (PP). A subset of cows (n = 6/group) in study 1 was blood sampled every 4 h over 48 h beginning on d 23 BEC, 9 BEC, and 5 PP. Body temperature was measured every 30 min (n = 8-16/treatment) for 48 h at 23 BEC and 9 BEC in both studies; and at 14 PP and 60 PP only in study 2. Treatment did not affect levels of CORT, GH, or P4 at 0600 h, but overall level of 5HT was lower and MEL higher in PS cows across days sampled. A 2-component versus single-component cosinor model better described [>coefficient of determination (R2);

ARRDC5 expression is conserved in mammalian testes and required for normal sperm morphogenesis.

In sexual reproduction, sperm contribute half the genomic material required for creation of offspring yet core molecular mechanisms essential for their formation are undefined. Here, the α-arrestin molecule arrestin-domain containing 5 (ARRDC5) is identified as an essential regulator of mammalian spermatogenesis. Multispecies testicular tissue transcriptome profiling indicates that expression of Arrdc5 is testis enriched, if not specific, in mice, pigs, cattle, and humans. Knockout of Arrdc5 in mice leads to male specific sterility due to production of low numbers of sperm that are immotile and malformed. Spermiogenesis, the final phase of spermatogenesis when round spermatids transform to spermatozoa, is defective in testes of Arrdc5 deficient mice. Also, epididymal sperm in Arrdc5 knockouts are unable to capacitate and fertilize oocytes. These findings establish ARRDC5 as an essential regulator of mammalian spermatogenesis. Considering the role of arrestin molecules as modulators of cellular signaling and ubiquitination, ARRDC5 is a potential male contraceptive target.