The vesicular monoamine transporter 2 (VMAT2) is localized primarily within the CNS and is responsible for transporting monoamines from the cytoplasm into secretory vesicles. Because reserpine (a VMAT inhibitor) can precipitate depressive-like symptoms in humans, we investigated whether Vmat2 heterozygous (HET) mice present with depressive-like behaviors. The mutants showed locomotor and rearing retardation in the open field and appeared anhedonic to 1 and 1.5% sucrose solutions. Immobility times for Vmat2 heterozygotes were prolonged in forced swim and imipramine normalized this behavior. HET animals also showed enhanced immobility in tail suspension and this response was alleviated by fluoxetine, reboxetine, and bupropion. Stimulated GTP␥S binding indicated that ␣ 2 -adrenergic receptors in HET hippocampus were more sensitive to UK 14,304 (5-bromo-N-(4,5-dihydro-1-H-imidazol-2-yl)-6-quinoxalinamine) stimulation than in wild type (WT) mice. In learned helplessness, mice were exposed to a shuttle box for 4 d or were given inescapable foot-shocks for the same time period. On day 5, all animals were tested in shock escape. Failure rates and the latency to escape were similar for WT and HET mice that were only pre-exposed to the test apparatus. In foot-shock groups, learned helplessness was more robust in heterozygotes than in WT controls. Basal secretion of serum corticosterone was not distinguished by genotype; however, corticosterone levels in mutants were more responsive to stress. Anxiety-like responses of WT and HET animals in the open field, light-dark exploration, zero maze, and novelty-suppressed feeding tests were indistinguishable. Collectively, these findings suggest that Vmat2 heterozygotes display a depressive-like phenotype that is devoid of anxiety-like behavior.

A carboxypeptidase E (CPE) knockout (KO) mouse was generated by deletion of exons 4 and 5 from the CPE gene, and its phenotype was characterized. KO mice became obese by 10-12 wk of age and reached 60-80 g by 40 wk. At this age, body fat content was more than double that in the wild-type (WT) controls. The null animals consumed more food overall, were less physically active during the light phase of the light-dark cycle, and burned fewer calories as fat than WT littermates. Fasting levels of glucose and insulin-like immunoreactivity in plasma were elevated in both male and female KO mice at approximately 20 wk; males recovered fully and females partially from this state by 32 wk. At this time, insulin-like immunoreactivity in the plasma, identified as proinsulin, was 50-100 times higher than that of the WT animals. The KO mice showed impaired glucose clearance and were insulin resistant. High levels of leptin and no circulating fully processed cocaine- and amphetamine-related transcript, a peptide that is responsive to leptin-induced feedback inhibition of feeding, were found in serum. The KO mice were subfertile and showed deficits in GnRH processing in the hypothalamus. Behavioral analyses revealed that KO animals showed diminished reactivity to stimuli and had reduced muscle strength and coordination, as well as visual placing and toe-pinch reflexes. These data demonstrate that CPE KO mice display a wide range of neural and endocrine abnormalities and suggest that CPE may have additional physiological roles beyond those ascribed to peptide processing and sorting of prohormones in cells.

Background The number of oocytes retrieved does not always coincide with the number of follicles aspirated in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment. Patients with high expectation of retrieval sometimes obtain few oocytes, which may be induced by improper operation or therapeutic factors. The purpose of this study was to evaluate the distribution data of oocyte retrieval rate (ORR) and to explore the risk factors for low ORR in patients with polycystic ovary syndrome (PCOS) undergoing IVF/ICSI. Methods A total of 2478 patients with PCOS undergoing IVF/ICSI were involved in this retrospective case-control study from March 2016 to October 2021. The oocyte retrieval rate was calculated as the ratio of the number of obtained oocytes to the number of follicles (≥ 12 mm) on the trigger day. Patients were divided into a low ORR and a normal ORR group with the boundary of one standard deviation from the mean value of ORR. The patient characteristics, treatment protocols, serum hormone levels, and embryonic and pregnancy outcomes were analyzed. Results The ORR exhibited a non-normal distribution, with a median of 0.818. The incidence of complete empty follicle syndrome was 0.12% (3/2478). The proportion of patients in the low ORR group who received the progestin-primed protocol was significantly higher than that in the normal ORR group (30.30% vs. 17.69%). A logistic regression analysis showed that the serum estradiol level/follicle (≥ 12 mm) ratio (OR: 0.600 (0.545–0.661)) and progesterone level (OR: 0.783 (0.720–0.853)) on the trigger day were significant factors in the development of a low ORR, with optimal cutoff values of 172.85 pg/ml and 0.83 ng/ml, respectively, as determined by receiver operating curve. Fewer high-quality embryos (2 vs. 5) and more cycles with no available embryos (5.42% vs. 0.43%) were found in the low ORR group. Conclusions For patients with PCOS, low estradiol levels/follicles (≥ 12 mm) and progesterone levels on the trigger day and the use of the progestin-primed protocol could be risk factors for low ORR, which leads to a limited number of embryos and more cycle cancellations.