ABSTRAcT. The odor preference of female mice for male odor is reported to have cyclical variations in relation to the estrus cycle. Females prefer the odor of genetically dissimilar males to that of genetically similar ones, but the causal relation between this preference and the estrus cycle has scarcely been investigated. The Y-maze test demonstrated that BALB/c females stayed for a longer duration near the urine of c57BL/6 males than that of BALB/c males when they were in metestrus, diestrus and proestrus, but not in estrus. The prolonged stay disappeared after ovariectomy, and administration of estradiol-17β restored the tendency. The present results suggest that the odor preference of BALB/c females for c57BL/6 over BALB/c males temporally changes according to the estrus cycle and that estrogen can be one of endogenous factors regulating this phenomenon.

Inbreeding avoidance is essential to providing offspring with genetic diversity. Females' mate choice is more crucial than males' for successful reproduction because of the high cost of producing gametes and limited chances to mate. However, the mechanism of female inbreeding avoidance is still unclear. To elucidate the mechanism underlying inbreeding avoidance by females, we conducted Y-maze behavioral assays using BALB/c and C57BL/6 female mice. In both strains, the avoidance of male urine from the same strain was lower in the low estrogen phase than in the high estrogen phase. The estrous cycle-dependent avoidance was completely prevented by vomeronasal organ (VNO) removal. To assess the regulation of the vomeronasal system by estrogen, the neural excitability was evaluated by immunohistochemistry of the immediate early gene products. Although estrogen did not affect neural excitability in the VNO, estrogen enhanced the neural excitability of the mitral cell layer in the AOB induced by urine from the cognate males. These results suggest that female mice avoid odor from genetically similar males in an estrogen-dependent manner via the vomeronasal system and the excitability of the mitral cells in the AOB is presumed to be regulated by estrogen.

Objective:We aimed to investigate the changes in blood glucose levels, body weight, and metabolic and circulatory parameters during daily administration of the sodium-glucose cotransporter 2 inhibitor, dapagliflozin, as well as to examine its safety and the factors that predict its effects on blood glucose and body weight in a retrospective, multicenter study conducted at 6 medical institutions in the Chikushi region of Kyushu, Japan.Methods: A total of 112 people with type 2 diabetes treated with dapagliflozin participated in the study. Data from blood tests, physical measurements, and other parameters obtained during outpatient visits at the start and after 12 months were retrospectively analyzed to evaluate the efficacy and safety. Results:The mean age of patients was 56.7 ± 9.9 years (mean ± standard deviation). The glycated hemoglobin (HbA1c) and body mass index (BMI) at baseline were 8.1 ± 1.2% and 29.2 ± 4.6 kg/m 2 , respectively. Significant reduction was observed in HbA1c (0.66%) and body weight (2.9 kg) (p<0.01) with dapagliflozin administration. After 12 months, blood pressure, liver function parameters (aspartate aminotransferase [AST], alanine aminotransferase [ALT], γ-glutamyl transpeptidase [γ-GTP]), uric acid, lipid profile (p<0.05) were significantly improved. Multiple regression analyses showed that high baseline HbA1c affected the improvement of HbA1c. Additionally, female sex and long disease duration affected BMI improvement. Regarding the safety, none of the 112 subjects exhibited severe adverse effects related to dapagliflozin, and no clinically meaningful changes were observed in the data from blood tests and physical measurements obtained during outpatient visits. Conclusion:This multicenter study conducted at medical institutions in the Chikushi region of Kyushu confirmed the efficacy and safety of dapagliflozin in clinical practice. We identified baseline HbA1c level as a factor that affected the change in HbA1c, and sex and disease duration as factors affecting the change in BMI.Body weight significantly decreased from 77.3 ± 12.8 kg at the start of dapagliflozin administration to 76.0 ± 12.7, 75.0 ± 12.7, 74.6 ± 12.9,