Estrus

Although both males and females become addicted to cocaine, females transition to addiction faster and experience greater difficulties remaining abstinent. We demonstrate an oestrous cycle-dependent mechanism controlling increased cocaine reward in females. During oestrus, ventral tegmental area (VTA) dopamine neuron activity is enhanced and drives post translational modifications at the dopamine transporter (DAT) to increase the ability of cocaine to inhibit its function, an effect mediated by estradiol. Female mice conditioned to associate cocaine with contextual cues during oestrus have enhanced mesolimbic responses to these cues in the absence of drug. Using chemogenetic approaches, we increase VTA activity to mechanistically link oestrous cycle-dependent enhancement of VTA firing to enhanced cocaine affinity at DAT and subsequent reward processing. These data have implications for sexual dimorphism in addiction vulnerability and define a mechanism by which cellular activity results in protein alterations that contribute to dysfunctional learning and reward processing.

Puberty is a key developmental event whose primary regulatory mechanisms remain poorly understood. Precise dating of puberty is crucial for experimental (preclinical) studies on its complex neuroendocrine controlling networks. In female laboratory rodents, external signs of puberty, such as vaginal opening (VO) and epithelial cell cornification (i.e., first vaginal estrus, FE), are indirectly related to the maturational state of the ovary and first ovulation, which is the unequivocal marker of puberty. Whereas in rats, VO and FE are almost simultaneous with the first ovulation, these events are not so closely associated in mice. Moreover, external signs of puberty can be uncoupled with first ovulation in both species under certain experimental conditions. We propose herein the Pubertal Ovarian Maturation Score (Pub-score), as novel, reliable method to assess peripubertal ovarian maturation in rats and mice. This method is founded on histological evaluation of pre-pubertal ovarian maturation, based on antral follicle development, and the precise timing of first ovulation, by retrospective dating of maturational and regressive changes in corpora lutea. This approach allows exact timing of puberty within a time-window of at least two weeks after VO in both species, thus facilitating the identification and precise dating of advanced or delayed puberty under various experimental conditions.

In women, endometrial breakdown, which is experienced as menstruation, is characterised by high concentrations of inflammatory mediators and immune cells which account for ~40% of the stromal compartment during tissue shedding. These inflammatory cells are known to play a pivotal role in tissue breakdown but their contribution to the rapid scarless repair of endometrium remains poorly understood. In the current study we used a mouse model of menstruation to investigate dynamic changes in mononuclear phagocytes during endometrial repair and remodelling. Menstruation was simulated in MacGreen mice to allow visualisation of CSF1R+ mononuclear phagocytes. Immunohistochemistry revealed dynamic spatio-temporal changes in numbers and location of CSF1R-EGFP+ cells and Ly6G+ neutrophils. Flow cytometry confirmed a striking increase in numbers of GFP+ cells during repair (24 h): influxed cells were 66% F4/80+Gr-1+ and 30% F4/80-Gr-1+. Immunostaining identified distinct populations of putative 'classical' monocytes (GFP+F4/80-), monocyte-derived macrophages (GFP+F4/80+) and a stable population of putative tissue-resident macrophages (GFP-F4/80+) localised to areas of breakdown, repair and remodelling respectively. Collectively, these data provide the first compelling evidence to support a role for different populations of monocytes/macrophages in endometrial repair and provide the platform for future studies on the role of these cells in scarless healing.

This study aimed to evaluate the accuracy of the accelerometer-equipped collar RUMI to detect estrus in dairy cows, establish a recommendation for the optimal timing for artificial insemination (AI) when using this device, and characterize the blood flow of the dominant follicle (F) and the corpus luteum (CL) as ovulation approaches. Forty-seven cycling cows were monitored following synchronization with a modified G6G protocol, allowing for spontaneous ovulation. Ultrasound examinations were conducted every 12 h, starting 48 h after the second PGF2α dose, to monitor uterine and ovarian changes. Blood samples were also collected to determine serum progesterone (P4) levels. Each cow was fitted with a RUMI collar, which continuously monitored behavioral changes to identify the onset, offset, and peak of activity of estrus. One-way ANOVA assessed the relationship between physiological parameters and time before ovulation. Results showed that the RUMI collar demonstrated high specificity (100%), sensitivity (90.90%), and accuracy (93.62%) for estrus detection. The optimal AI window was identified as between 11.4 and 15.5 h after heat onset. Increased blood flow to the F and reduced luteal activity were observed in the 48 h prior to ovulation. Further research is needed to assess the influence of this AI window on conception rates, and if it should be modified considering external factors.