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Animals : An Open Access Journal From... Mar 2024Progesterone-related diabetes mellitus (PRDM) in dogs is known for its particular potential for diabetes remission. This narrative review aims to provide relevant... (Review)
Review
Progesterone-related diabetes mellitus (PRDM) in dogs is known for its particular potential for diabetes remission. This narrative review aims to provide relevant detailed information on (1) the canine estrus cycle and its impact on canine diabetes mellitus (CDM) etiology and management, (2) the role of pyometra as a further cause of insulin resistance, and (3) useful individual therapeutic and preventive strategies. PRDM is recognized due to diestrus, exogenous progestogen exposure, pregnancy, and P4-production ovarian dysfunction. Pyometra represents additional inflammatory and septic negative influence on insulin sensitivity, and its diagnosis associated with CDM is therapeutically challenging. The estrus cycle's hormone fluctuations seem to modulate peripheric insulin sensibility by influencing insulin receptor (IR) affinity and its binding capacity, as well as modulating tyrosine kinase activity. Pyometra was shown to negatively influence IR compensatory mechanisms to insulin resistance causing glucose intolerance. Spaying and pregnancy termination may cause diabetes remission in PRDM cases in a median time of 10 days (1-51). Pharmacological annulment of progesterone effects may benefit patients unable to undergo surgery; however, remission chances are virtually null. The ALIVE (Agreeing Language in Veterinary Endocrinology) project proposed new criteria for CDM diagnoses and subclinical diabetes recognition. These new concepts may increase the frequency of a PRDM diagnosis and, even more, its relevance. Spaying represents a preventive measure against pyometra and PRDM that should be individually assessed in light of its recognized benefits and harms.
PubMed: 38539988
DOI: 10.3390/ani14060890 -
Pharmacology, Biochemistry, and Behavior Jun 2024Pituitary lactotrophs are under tonic dopaminergic inhibitory control and bromocriptine treatment blocks prolactin secretion.
BACKGROUND
Pituitary lactotrophs are under tonic dopaminergic inhibitory control and bromocriptine treatment blocks prolactin secretion.
METHODS
Sleep and local field potential were addressed for 72 h after bromocriptine treatments applied during the different stages of the estrus cycle and for 24 h in the early- and middle postpartum period characterized by spontaneously different dynamics of prolactin release in female rats.
RESULTS
Sleep changes showed strong dependency on the estrus cycle phase of the drug application. Strongest increase of wakefulness and reduction of slow wave sleep- and rapid eye movements sleep appeared during diestrus-proestrus and middle postpartum treatments. Stronger sleep-wake effects appeared in the dark phase in case of the estrus cycle treatments, but in the light phase in postpartum treatments. Slow wave sleep and REM sleep loss in case of estrus cycle treatments was not compensated at all and sleep loss seen in the first day post-injection was gained further later. In opposition, slow wave sleep loss in the light phase after bromocriptine injections showed compensation in the postpartum period treatments. Bromocriptine treatments resulted in a depression of local field potential delta power during slow wave sleep while an enhancement in beta and gamma power during wakefulness regardless of the treatment timing.
CONCLUSIONS
These results can be explained by the interplay of dopamine D2 receptor agonism, lack of prolactin release and the spontaneous homeostatic sleep drive being altered in the different stages of the estrus cycle and the postpartum period.
Topics: Animals; Bromocriptine; Female; Postpartum Period; Rats; Receptors, Dopamine D2; Dopamine Agonists; Estrous Cycle; Rats, Wistar; Sleep; Wakefulness; Prolactin
PubMed: 38537873
DOI: 10.1016/j.pbb.2024.173754 -
Biological Psychiatry Global Open... May 2024Cocaine-induced plasticity in the nucleus accumbens shell of males occurs primarily in dopamine D receptor-expressing medium spiny neurons (D1R-MSNs), with little if any...
BACKGROUND
Cocaine-induced plasticity in the nucleus accumbens shell of males occurs primarily in dopamine D receptor-expressing medium spiny neurons (D1R-MSNs), with little if any impact on dopamine D receptor-expressing medium spiny neurons (D2R-MSNs). In females, the effect of cocaine on accumbens shell D1R- and D2R-MSN neurophysiology has yet to be reported, nor have estrous cycle effects been accounted for.
METHODS
We used a 5-day locomotor sensitization paradigm followed by a 10- to 14-day drug-free abstinence period. We then obtained ex vivo whole-cell recordings from fluorescently labeled D1R-MSNs and D2R-MSNs in the nucleus accumbens shell of male and female mice during estrus and diestrus. We examined accumbens shell neuronal excitability as well as miniature excitatory postsynaptic currents (mEPSCs).
RESULTS
In females, we observed alterations in D1R-MSN excitability across the estrous cycle similar in magnitude to the effects of cocaine in males. Furthermore, cocaine shifted estrous cycle-dependent plasticity from intrinsic excitability changes in D1R-MSNs to D2R-MSNs. In males, cocaine treatment produced the anticipated drop in D1R-MSN excitability with no effect on D2R-MSN excitability. Cocaine increased mEPSC frequencies and amplitudes in D2R-MSNs from females in estrus and mEPSC amplitudes of D2R-MSNs from females in diestrus. In males, cocaine increased both D1R- and D2R-MSN mEPSC amplitudes with no effect on mEPSC frequencies.
CONCLUSIONS
Overall, while there are similar cocaine-induced disparities regarding the relative excitability of D1R-MSNs versus D2R-MSNs between the sexes, this is mediated through reduced D1R-MSN excitability in males, whereas it is due to heightened D2R-MSN excitability in females.
PubMed: 38533248
DOI: 10.1016/j.bpsgos.2024.100295 -
Journal of Ovarian Research Mar 2024It is well described that circulating progesterone (P4) plays a key role in several reproductive events such as oocyte maturation. However, during diestrus, when...
Corpus luteum presence in the bovine ovary increase intrafollicular progesterone concentration: consequences in follicular cells gene expression and follicular fluid small extracellular vesicles miRNA contents.
BACKGROUND
It is well described that circulating progesterone (P4) plays a key role in several reproductive events such as oocyte maturation. However, during diestrus, when circulating P4 is at the highest concentrations, little is known about its local impact on the follicular cells such as intrafollicular P4 concentration due to corpus luteum (CL) presence within the same ovary. Based on that, our hypothesis is that the CL presence in the ovary during diestrus alters intrafollicular P4 concentrations, oocyte competence acquisition, follicular cells gene expression, and small extracellular vesicles (sEVs) miRNAs contents.
RESULTS
P4 hormonal analysis revealed that ipsilateral to the CL follicular fluid (iFF) presented higher P4 concentration compared to contralateral follicular fluid (cFF). Furthermore, oocyte maturation and miRNA biogenesis pathways transcripts (ADAMTS-1 and AGO2, respectively) were increased in cumulus and granulosa cells of iFF, respectively. Nevertheless, a RT-PCR screening of 382 miRNAs showed that three miRNAs were upregulated and two exclusively expressed in sEVs from iFF and are predicted to regulate cell communication pathways. Similarly, seven miRNAs were higher and two exclusively expressed from cFF sEVs and are predicted to modulate proliferation signaling pathways.
CONCLUSION
In conclusion, intrafollicular P4 concentration is influenced by the presence of the CL and modulates biological processes related to follicular cell development and oocyte competence, which may influence the oocyte quality. Altogether, these results are crucial to improve our knowledge about the follicular microenvironment involved in oocyte competence acquisition.
Topics: Female; Animals; Cattle; Follicular Fluid; Progesterone; Ovarian Follicle; Ovary; MicroRNAs; Oocytes; Corpus Luteum; Extracellular Vesicles; Gene Expression
PubMed: 38500173
DOI: 10.1186/s13048-024-01387-3 -
Animals : An Open Access Journal From... Mar 2024The high-mobility group AT-hook 2() gene has been widely studied in the context of cancer and animal growth. However, recently, several studies have uncovered its...
The high-mobility group AT-hook 2() gene has been widely studied in the context of cancer and animal growth. However, recently, several studies have uncovered its critical role in cell proliferation. A genome-wide association study (GWAS) further suggests that the gene is a candidate gene in fertility, indicating its connection not only to growth traits but also to reproduction, specifically ovarian traits. Thus, this study aimed to analyze the distribution of the gene in 54 bovine breeds worldwide, identify important short fragment variants (indels), and investigate the relationship between and ovarian development. The dataset included genotypic information from a bovine population of 634 individuals (n = 634). After genotyping and analyzing four selected loci, we found that one out of four loci, rs133750033 (P4-D), was polymorphic. Our results also reveal that this indel of is significantly associated with certain ovarian traits ( 0.05). Specifically, it has connection with ovarian length ( = 0.004) and ovarian height ( = 0.026) during diestrus. Additionally, we discovered a higher expression of the gene in Asian cattle breeds. In summary, this study suggests that has the potential to serve as an animal fertility testing marker gene. Moreover, these findings contribute to a more promising outlook for the bovine industry.
PubMed: 38473181
DOI: 10.3390/ani14050796 -
Animals : An Open Access Journal From... Mar 2024The fertility rate and litter size of female pigs are critically affected by the expression of estrus. The objective of this study was to elucidate the regulatory...
The fertility rate and litter size of female pigs are critically affected by the expression of estrus. The objective of this study was to elucidate the regulatory mechanisms of estrus expression by analyzing the differential expression of genes and long intergenic non-coding RNAs (lincRNA), as well as the utilization of alternative polyadenylation (APA) sites, in the vulva and vagina during the estrus and diestrus stages of Large White and indigenous Chinese Mi gilts. Our study revealed that the number of differentially expressed genes (DEG) in the vulva was less than that in the vagina, and the DEGs in the vulva were enriched in pathways such as "neural" pathways and steroid hormone responses, including the "Calcium signaling pathway" and "Oxytocin signaling pathway". The DEGs in the vagina were enriched in the "Metabolic pathways" and "VEGF signaling pathway". Furthermore, 27 and 21 differentially expressed lincRNAs (DEL), whose target genes were enriched in the "Endocrine resistance" pathway, were identified in the vulva and vagina, respectively. Additionally, we observed that 63 and 618 transcripts of the 3'-untranslated region (3'-UTR) were lengthened during estrus in the vulva and vagina, respectively. Interestingly, the genes undergoing APA events in the vulva exhibited species-specific enrichment in neural or steroid-related pathways, whereas those in the vagina were enriched in apoptosis or autophagy-related pathways. Further bioinformatic analysis of these lengthened 3'-UTRs revealed the presence of multiple miRNAs binding sites and cytoplasmic polyadenylation element (CPE) regulatory aspects. In particular, we identified more than 10 CPEs in the validated lengthened 3'-UTRs of the , , and genes using RT-qPCR. These findings demonstrated the involvement of APA and lincRNAs in the regulation of estrus expression in female pigs, providing new insights into the molecular mechanisms underlying estrus expression in pigs.
PubMed: 38473176
DOI: 10.3390/ani14050791 -
Scientific Reports Mar 2024The estrus cycle in female rodents has been shown to affect a variety of physiological functions. However, little is known about its presumably thorough effect on...
The estrus cycle in female rodents has been shown to affect a variety of physiological functions. However, little is known about its presumably thorough effect on auditory processing during the sleep-wake cycle and sleep deprivation. Vertex auditory evoked potentials (vAEPs) were evoked by single click tone stimulation and recorded during different stages of the estrus cycle and sleep deprivation performed in metestrus and proestrus in female rats. vAEPs showed a strong sleep-dependency, with the largest amplitudes present during slow wave sleep while the smallest ones during wakefulness. Higher amplitudes and longer latencies were seen in the light phase during all vigilance stages. The largest amplitudes were found during proestrus (light phase) while the shortest latencies were seen during estrus (dark phase) compared to the 2nd day diestrus baseline. High-amplitude responses without latency changes were also seen during metestrus with increased homeostatic sleep drive. More intense and faster processing of auditory information during proestrus and estrus suggesting a more effective perception of relevant environmental cues presumably in preparation for sexual receptivity. A 4-h sleep deprivation resulted in more pronounced sleep recovery in metestrus compared to proestrus without difference in delta power replacement suggesting a better tolerance of sleep deprivation in proestrus. Sleep deprivation decreased neuronal excitability and responsiveness in a similar manner both during metestrus and proestrus, suggesting that the negative consequences of sleep deprivation on auditory processing may have a limited correlation with the estrus cycle stage.
Topics: Rats; Female; Animals; Sleep Deprivation; Estrus; Metestrus; Proestrus; Diestrus
PubMed: 38461157
DOI: 10.1038/s41598-024-56392-9 -
BioRxiv : the Preprint Server For... Apr 2024Uterine contraction patterns vary during the ovulatory cycle and throughout pregnancy but prior measurements have produced limited and conflicting information on these...
Uterine contraction patterns vary during the ovulatory cycle and throughout pregnancy but prior measurements have produced limited and conflicting information on these patterns. We combined a virally delivered genetically encoded calcium reporter (GCaMP8m) and ultra-widefield imaging in live nonpregnant mice to characterize uterine calcium dynamics at organ scale throughout the estrous cycle. Prior to ovulation (proestrus and estrus) uterine excitations primarily initiated in a region near the oviduct, but after ovulation (metestrus and diestrus), excitations initiated at loci homogeneously distributed throughout the organ. The frequency of excitation events was lowest in proestrus and estrus, higher in metestrus and highest in diestrus. These results establish a platform for mapping uterine activity, and show that the question of whether there is an anatomically localized trigger for uterine excitations depends on the estrous cycle phase.
PubMed: 38370720
DOI: 10.1101/2024.02.02.578395 -
Frontiers in Endocrinology 2023The impact of stress on reproductive function is significant. Hypothalamic paraventricular nucleus (PVN) corticotrophin-releasing hormone (CRH) plays a major role in...
INTRODUCTION
The impact of stress on reproductive function is significant. Hypothalamic paraventricular nucleus (PVN) corticotrophin-releasing hormone (CRH) plays a major role in regulating the stress response. Understanding how the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-gonadal (HPG) axis interact is crucial for comprehending how stress can lead to reproductive dysfunction. However, whether stress influences reproductive function via modulating PVN CRH or HPA sequelae is not fully elucidated.
METHODS
In this study, we investigated the impact of chemogenetic activation of PVN CRH neurons on reproductive function. We chronically and selectively stimulated PVN CRH neurons in female CRH-Cre mice using excitatory designer receptor exclusively activated by designer drugs (DREADDs) viral constructs, which were bilaterally injected into the PVN. The agonist compound-21 (C21) was delivered through the drinking water. We determined the effects of DREADDs activation of PVN CRH neurons on the estrous cycles, LH pulse frequency in diestrus and metestrus and LH surge in proestrus mice. The effect of long-term C21 administration on basal corticosterone secretion and the response to acute restraint stress during metestrus was also examined. Additionally, computer simulations of a mathematical model were used to determine the effects of DREADDs activation of PVN CRH neurons, simulating chronic stress, on the physiological parameters examined experimentally.
RESULTS
As a result, and consistent with our mathematical model predictions, the length of the estrous cycle was extended, with an increase in the time spent in estrus and metestrus, and a decrease in proestrus and diestrus. Additionally, the frequency of LH pulses during metestrus was decreased, but unaffected during diestrus. The occurrence of the preovulatory LH surge during proestrus was disrupted. The basal level of corticosterone during metestrus was not affected, but the response to acute restraint stress was diminished after long-term C21 application.
DISCUSSION
These data suggest that PVN CRH neurons play a functional role in disrupting ovarian cyclicity and the preovulatory LH surge, and that the activity of the GnRH pulse generator remains relatively robust during diestrus but not during metestrus under chronic stress exposure in accordance with our mathematical model predictions.
Topics: Female; Animals; Mice; Paraventricular Hypothalamic Nucleus; Corticotropin-Releasing Hormone; Corticosterone; Estrous Cycle; Imidazoles; Sulfonamides; Thiophenes
PubMed: 38264285
DOI: 10.3389/fendo.2023.1322662 -
Animals : An Open Access Journal From... Jan 2024The genes encoding for estrogen receptor () and follicle-stimulating hormone receptor () play crucial roles in ovarian follicular development. This study aimed to...
The genes encoding for estrogen receptor () and follicle-stimulating hormone receptor () play crucial roles in ovarian follicular development. This study aimed to determine the expression levels of miRNAs predicted against and mRNAs in follicular cells related to their target genes during the estrous cycle in canines. Antral follicles were dissected from 72 ovaries following ovariohysterectomies. MiRNAs regulating and genes were selected from miRNA databases, and mature miRNA and mRNA expression profiling was performed using real-time polymerase chain reaction (PCR). The best miRNA for each target gene was selected considering the quantitative PCR (qPCR) performance and target prediction probability, selecting only miRNAs with a binding -value of 1.0, and choosing and for and , respectively. The expression levels comparing the different phases of the estrous cycle were evaluated using ANOVA. Pearson correlations between the expression pattern of each miRNA and their target genes were performed. Each miRNA and its target genes were expressed in the granulosa cells in all estrous phases. remained low in anestrus and proestrus, increased ( < 0.05) to the highest level in estrus, and decreased ( < 0.05) in diestrus. showed the same trend as , with the highest ( < 0.05) expression in estrus and the lowest ( < 0.05) in anestrus and proestrus. A tendency for an inverse relationship was observed between the expression of and only in the anestrus phase, while an inverse correlation (r = -0.8) was found between and ( < 0.01). The expression profile of and and their predicted target genes of dog ovarian follicles throughout the estrous cycle observed in this study suggest a role in the transcriptional regulation of and , which is the first evidence of the involvement of these miRNAs in the canine follicular function.
PubMed: 38254383
DOI: 10.3390/ani14020214