Mechanism Of Leptin On Impaired Ovarian Reserve Function After Cold Exposure In Female Rats

Previous studies have shown that cold exposure can cause disturbance of estrus cycle in female rats. However, whether cold exposure can cause organic pathological damage to the reproductive system of female rats was undefined. Meanwhile there are few reports on the mechanism of decompensation in rat reproductive function after cold exposure. This study aims to further discuss how cold exposure impact female ovarian reserve function in rats. Female rats were randomly divided into control group and cold exposure group. Ovarian reserve function, differential genes in hypothalamus reproductive regulation center or peripheral were evaluated. After cold exposure, ovarian reserve function was impaired, follicle development was abnormal, the number of mature follicles decreased significantly, the key hypothalamic reproductive regulation molecule GnRH decreased significantly, the response of its regulatory receptor NPY-5R was down-regulated, and the peripheral hormone serum leptin, which is closely related to it, decreased significantly. Our results indicate that cold exposure can lead to impaired ovarian function in female rats, resulting from decrease in serum leptin cause by WAT leptin depletion, which can release the inhibitory of NPY in the hypothalamus, and further lead to the down-regulation of GnRH expression, resulting in the whole HPO axis.

Sex differences in metabolic pathways are regulated by Pfkfb3 and Pdk4 expression in rodent muscle

Skeletal muscles display sexually dimorphic features. Biochemically, glycolysis and fatty acid β-oxidation occur preferentially in the muscles of males and females, respectively. However, the mechanisms of the selective utilization of these fuels remains elusive. Here, we obtain transcriptomes from quadriceps type IIB fibers of untreated, gonadectomized, and sex steroid-treated mice of both sexes. Analyses of the transcriptomes unveil two genes, Pfkfb3 (phosphofructokinase-2) and Pdk4 (pyruvate dehydrogenase kinase 4), that may function as switches between the two sexually dimorphic metabolic pathways. Interestingly, Pfkfb3 and Pdk4 show male-enriched and estradiol-enhanced expression, respectively. Moreover, the contribution of these genes to sexually dimorphic metabolism is demonstrated by knockdown studies with cultured type IIB muscle fibers. Considering that skeletal muscles as a whole are the largest energy-consuming organs, our results provide insights into energy metabolism in the two sexes, during the estrus cycle in women, and under pathological conditions involving skeletal muscles.

Alveolar progenitor differentiation and lactation depends on paracrine inhibition of notch via ROBO1/CTNNB1/JAG1

ABSTRACT In the mammary gland, how alveolar progenitor cells are recruited to fuel tissue growth with each estrus cycle and pregnancy remains poorly understood. Here, we identify a regulatory pathway that controls alveolar progenitor differentiation and lactation by governing Notch activation in mouse. Loss of Robo1 in the mammary gland epithelium activates Notch signaling, which expands the alveolar progenitor cell population at the expense of alveolar differentiation, resulting in compromised lactation. ROBO1 is expressed in both luminal and basal cells, but loss of Robo1 in basal cells results in the luminal differentiation defect. In the basal compartment, ROBO1 inhibits the expression of Notch ligand Jag1 by regulating β-catenin (CTNNB1), which binds the Jag1 promoter. Together, our studies reveal how ROBO1/CTTNB1/JAG1 signaling in the basal compartment exerts paracrine control of Notch signaling in the luminal compartment to regulate alveolar differentiation during pregnancy.

Activated Human Umbilical Cord Blood Platelet-Rich Plasma Enhances the Beneficial Effects of Human Umbilical Cord Mesenchymal Stem Cells in Chemotherapy-Induced POF Rats

Saving the ovarian function of premature ovarian failure (POF) patients undergoing chemotherapy is an important problem in the field of reproductive medicine. At present, human umbilical cord mesenchymal stem cells (HucMSCs) have been used in the treatment of POF, but the effect is still not optimal. The purpose of this study was to determine whether human umbilical cord blood platelet-rich plasma (ucPRP) enhances the beneficial effects of HucMSCs in the treatment of POF. First, we observed the effects of changes in the biological activity of ucPRP on HucMSCs in vitro. Subsequently, we tracked the distribution and function of the HucMSCs in POF rats, and the rats’ estrus cycle and serum sex hormones, follicular development, ovarian angiogenesis, ovarian granulosa cell proliferation, and apoptosis were assessed. The results of the study showed that the addition of ucPRP in vitro accelerates proliferation and reduces apoptosis of the HucMSCs while upregulating the stemness gene of the HucMSCs. The combined transplantation of HucMSCs and ucPRP resulted in more stem cells being retained in the ovaries of POF rats, the estrus cycle of the POF rats being restored, the levels of serum E2, AMH, and FSH improving, and damaged follicles beginning to grow. Finally, we confirmed that the potential mechanism of the combination of HucMSCs and ucPRP to rescue the ovarian function of POF rats is to promote ovarian angiogenesis and to promote the proliferation and reduce the apoptosis of ovarian granulosa cells. The upregulation of AMH and FHSR expression and the downregulation of caspase-3 expression in granulosa cells are potential mechanisms for the recovery of ovarian function. Our research results suggest that the combined application of HucMSCs and ucPRP is a safe and efficient transplantation program for the treatment of POF, thus providing a reliable experimental basis for the clinical application of stem cell therapy in POF.

Does the rate of orthodontic tooth movement change during the estrus cycle? A systematic review based on animal studies

Background As the fluctuation of sex hormone levels in menstruating women results in periodical effects in bone metabolism, understanding the implications for tooth movement could be of benefit to the orthodontist. This type of research presents practical and ethical problems in humans, but animal models could provide useful information. Our objective was to systematically investigate the available evidence on the question whether the rate of orthodontic tooth movement varies between the different stages of the estrus cycle in animals. Methods Unrestricted searches in 7 databases and manual searching of the reference lists in relevant studies were performed up to February 2021 (Medline [PubMed], CENTRAL [Cochrane Library; includes records from Embase, CINAHL, ClinicalTrials.gov, WHO's ICTRP, KoreaMed, Cochrane Review Groups’ Specialized Registers, and records identified by handsearching], Cochrane Database of Systematic Reviews [Cochrane Library], Scopus, Web of Knowledge [including Web of Science Core Collection, KCI Korean Journal Database, Russian Science Citation Index, SciELO Citation Index and Zoological Record], Arab World Research Source [EBSCO] and ProQuest Dissertation and Theses [ProQuest]). Our search focused on prospective controlled animal studies, whose samples included female subjects of any species that were quantitatively comparing the amount of tooth movement in the different stages of the estrus cycle. Following study retrieval and selection, relevant data was extracted, and the risk of bias was assessed using the SYRCLE’s Risk of Bias Tool. Results From the finally assessed records, 3 studies met the inclusion criteria. Two of the studies experimented on Wistar rats, whereas the other on cats. Tooth movement was induced by expansion or coil springs. The rate of orthodontic tooth movement was increased during the stages of the estrus cycle when oestrogen and/or progesterone levels were lower. The risk of bias in the retrieved studies was assessed to be unclear. Conclusion Hormonal changes during the estrus cycle may affect the rate of orthodontic tooth movement. Although these animal experiment results should be approached cautiously regarding their translational potential, it could be useful to consider the possible impact of these physiological changes in the clinical setting until more information becomes available. Registration: PROSPERO (CRD42021158069).

Proteomic determinants of uterine receptivity for pregnancy in early and mid-postpartum dairy cows†

Dairy cow subfertility is a worldwide issue arising from multiple factors. It manifests in >30% early pregnancy losses in seasonal pasture-grazed herds, especially when cows are inseminated in the early post-partum period. Most losses occur before implantation, when embryo growth depends on factors present in maternal tract fluids. Here we examined the proteomic composition of early and mid-postpartum uterine luminal fluid in crossbred lactating dairy cows to identify molecular determinants of fertility. We also explored changes in uterine luminal fluid from first to third estrus cycles postpartum in individual cows, linking those changes with divergent embryo development. For this, we flushed uteri of 87 cows at day 7 of pregnancy at first and third estrus postpartum, recovering and grading their embryos. Out of 1563 proteins detected, 472 had not been previously reported in this fluid, and 408 were predicted to be actively secreted by bioinformatic analysis. The abundance of 18 proteins with roles in immune regulation and metabolic function (e.g. cystatin B, pyruvate kinase M2) was associated with contrasting embryo quality. Matched-paired pathway analysis indicated that, from first to third estrus postpartum, upregulation of metabolic (e.g. creatine and carbohydrate) and immune (e.g. complement regulation, antiviral defense) processes were related to poorer quality embryos in the third estrus cycle postpartum. Conversely, upregulated signal transduction and protein trafficking appeared related to improved embryo quality in third estrus. These results advance the characterization of the molecular environment of bovine uterine luminal fluid and may aid understanding fertility issues in other mammals, including humans.

Time Mating Guinea Pigs by Monitoring Changes to the Vaginal Membrane throughout the Estrus Cycle and with Ultrasound Confirmation

One of the greatest challenges to the development and implementation of pregnancy therapeutics is the ability to rigorously test treatments in clinically relevant animal models. Guinea pigs offer a unique advantage in studying the placenta, fetal development, and reproductive health as they have similar developmental milestones to humans, both throughout gestation and following birth. Tracking the guinea pig estrus cycle is imperative to ensuring appropriately timed mating and can be performed by monitoring the guinea pig vaginal membrane. Here, we describe a methodology to efficiently and accurately time mate guinea pigs, and provide a picture representation of changes to the guinea pig vaginal membrane throughout the estrus cycle. Utilization of this monitoring enabled a 100% pregnancy success rate on the first mating attempt in a cohort of five guinea pigs. This approach, along with early pregnancy ultrasounds as a secondary method to confirm pregnancy, offers a reliable approach to timed mating in the guinea pig.