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BioRxiv : the Preprint Server For... Apr 2024Food intake varies across the stages of a rat's estrous cycle. It is reasonable to hypothesize that this cyclic fluctuation in consumption reflects an impact of hormones...
UNLABELLED
Food intake varies across the stages of a rat's estrous cycle. It is reasonable to hypothesize that this cyclic fluctuation in consumption reflects an impact of hormones on taste palatability/preference, but evidence for this hypothesis has been mixed, and critical within-subject experiments in which rats sample multiple tastes during each of the four main estrous phases (metestrus, diestrus, proestrus, and estrus) have been scarce. Here, we assayed licking for pleasant (sucrose, NaCl, saccharin) and aversive (quinine-HCl, citric acid) tastes each day for 5-10 days while tracking rats' estrous cycles through vaginal cytology. Initial analyses confirmed the previously-described increased consumption of pleasant stimuli 24-48 hours following the time of high estradiol. A closer look, however, revealed this effect to reflect a general magnification of palatability-higher than normal preferences for pleasant tastes and lower than normal preferences for aversive tastes-during metestrus. We hypothesized that this phenomenon might be related to estradiol processing in the lateral hypothalamus (LH), and tested this hypothesis by inhibiting LH estrogen receptor activity with ICI during tasting. Control infusions replicated the metestrus magnification of palatability pattern; ICI infusions blocked this effect as predicted, but failed to render preferences "cycle free," instead delaying the palatability magnification until diestrus. Clearly, estrous phase mediates details of taste palatability in a manner involving hypothalamic actions of estradiol; further work will be needed to explain the lack of a flat response across the cycle with hypothalamic estradiol binding inhibited, a result which perhaps suggests dynamic interplay between brain regions or hormones.
SIGNIFICANCE STATEMENT
Consummatory behaviors are impacted by many variables, including naturally circulating hormones. While it is clear that consumption is particularly high during the stages following the high-estradiol stage of the rodent's estrous (and human menstrual) cycle, it is as of yet unclear whether this phenomenon reflects cycle stage-specific palatability (i.e., whether pleasant tastes are particularly delicious, and aversive tastes particularly disgusting, at particular phases). Here we show that palatability is indeed modulated by estrous phase, and that this effect is governed, at least in part, by the action of estradiol within the lateral hypothalamus. These findings shed light on the mechanisms underlying the adverse impact on human welfare due to irregularities observed across the otherwise cyclic menstrual process.
PubMed: 38617267
DOI: 10.1101/2024.04.01.587593 -
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 -
Endocrinology Jan 2024The arcuate nucleus kisspeptin (ARNKISS) neurons represent the GnRH pulse generator that likely drives pulsatile gonadotropin secretion in all mammals. Using an improved...
The arcuate nucleus kisspeptin (ARNKISS) neurons represent the GnRH pulse generator that likely drives pulsatile gonadotropin secretion in all mammals. Using an improved GCaMP fiber photometry system enabling long-term continuous recordings, we aimed to establish a definitive profile of ARNKISS neuronal activity across the murine estrous cycle. As noted previously, a substantial reduction in the frequency of ARNKISS neuron synchronization events (SEs) occurs on late proestrus and extends into estrus. The SE amplitude remains constant throughout the cycle. During metestrus, we unexpectedly detected many multipeak SEs where many SEs occurred rapidly, within 160 seconds of each other. By applying a machine learning-based, k-means clustering analysis, we were further able to detect substantial within-stage variability in the patterns of pulse generator activity. Estrous cycle-dependent changes in SE activity occurred around the time of lights on and off. We also find that a mild stressor such as vaginal lavage reduces ARNKISS neuron SE frequency for up to 3 hours. These observations provide a comprehensive account of ARNKISS neuron activity across the estrous cycle, highlight a new pattern of multipeak SE activity, and introduce a new k-means clustering approach for analyzing ARNKISS neuron population behavior.
Topics: Animals; Female; Mice; Arcuate Nucleus of Hypothalamus; Estrous Cycle; Gonadotropin-Releasing Hormone; Kisspeptins; Luteinizing Hormone; Neurons
PubMed: 38279940
DOI: 10.1210/endocr/bqae009 -
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 -
Archives of Razi Institute Aug 2023Ginseng is known as the king of all herbs in terms of antioxidant and anti-inflammatory activities and recently has become more involved in the treatment of neurological...
Ginseng is known as the king of all herbs in terms of antioxidant and anti-inflammatory activities and recently has become more involved in the treatment of neurological diseases. In this regard, this study aimed to determine the effects of on pentylenetetrazol-induced epilepsy during the estrus cycle. For this purpose, 30 rats were randomly divided into five groups, namely control (saline), valproic acid (VPA, 75 mg/kg), (50 mg/kg), (100 mg/kg), and (150 mg/kg) with four subgroups (proestrus, estrus, metestrus, and diestrus). Subsequently, the initiation time of myoclonic seizures (ITMS), initiation time of tonic-clonic seizures (ITTS), and seizure duration (SD) were determined. According to the results, ITMS and ITTS significantly increased in the VPA-treated group (<0.05). (100 and 150 mg/kg) administration significantly increased ITMS and ITTS (<0.05). Moreover, the ITMS and ITTS in -treated rats were significantly higher in luteal phases, compared to the follicular phase (<0.05). In addition, pretreatment with VPA significantly decreased SD, compared to the control group (<0.05). A significant decrease in SD was observed in the rats pretreated with (100 and 150 mg/kg) (<0.05). Seizure duration significantly decreased in animals that received in luteal phases, compared to the follicular phase (<0.05). These results suggested that have anticonvulsant effects that are more prominent during the luteal phase than the follicular phase.
Topics: Animals; Female; Rats; Anticonvulsants; Estrus; Ginsenosides; Pentylenetetrazole; Seizures; Valproic Acid
PubMed: 38226383
DOI: 10.32592/ARI.2023.78.4.1359 -
Archives of Razi Institute Jun 2023Because of the mutual relationship between neural inflammation and seizure, this study aimed to determine the effects of intracerebroventricular (ICV) injection of the...
Because of the mutual relationship between neural inflammation and seizure, this study aimed to determine the effects of intracerebroventricular (ICV) injection of the steroidal and non-steroidal anti-inflammatory drugs on pentylenetetrazol (PTZ)-induced seizures during the estrous cycle in rats. A total of 105 adult female Wistar rats were selected and divided into seven groups, including the control (saline), ketorolac tris salt (7.5, 15, and 30 µg), and methylprednisolone acetate (0.15, 0.3, and 0.6 µg), each with four subgroups (proestrus, estrus, metestrus, and diestrus) and three replicates (n=5). After a week of acclimatization, the estrous phase determination and synchronization were performed. Acute epilepsy was inspired by the intraperitoneal injection of 80 mg/kg of PTZ 30 min after the ICV injection of ketorolac and methylprednisolone acetate. The initiation time of myoclonic seizures (ITMS), the initiation time of tonic-clonic seizures (ITTS), seizure duration (SD), and mortality rate (MR) were measured for 30 min. Data were shown as mean±SD and analyzed using One-way ANOVA followed by Tukey-Kramer multiple comparison post hoc test (<0.05). According to the results, ketorolac (15 and 30 µg) and methylprednisolone acetate (0.3 and 0.6 µg) significantly increased the ITTS and ITMS but decreased SD during the estrous cycle, compared to the control (<0.05). Moreover, MR and SD were significantly decreased by ketorolac (7.5, 15, and 30 µg) and methylprednisolone (0.3 and 0.6 µg), compared to the control during the estrous cycle (<0.05). Therefore, it seems that both ketorolac and methylprednisolone possess dose-dependent anticonvulsant effects that may decrease neural inflammation.
Topics: Rats; Female; Animals; Rats, Wistar; Ketorolac; Methylprednisolone Acetate; Estrous Cycle; Seizures; Inflammation; Anti-Inflammatory Agents
PubMed: 38028823
DOI: 10.22092/ARI.2022.360115.2553 -
BMC Neuroscience Nov 2023Female sex is a known risk factor of brain disorders with raised intracranial pressure (ICP) and sex hormones have been suggested to alter cerebrospinal fluid (CSF)...
BACKGROUND
Female sex is a known risk factor of brain disorders with raised intracranial pressure (ICP) and sex hormones have been suggested to alter cerebrospinal fluid (CSF) dynamics, thus impairing ICP regulation in CSF disorders such as idiopathic intracranial hypertension (IIH). The choroid plexus (CP) is the tissue producing CSF and it has been hypothesized that altered hormonal composition could affect the activity of transporters involved in CSF secretion, thus affecting ICP. Therefore, we aimed to investigate if expression of various transporters involved in CSF secretion at CP were different between males and females and between females in different estrous cycle states. Steroid levels in serum was also investigated.
METHODS
Female and male rats were used to determine sex-differences in the genes encoding for the transporters Aqp1 and 4, NKCC1, NBCe2, NCBE; carbonic anhydrase enzymes II and III (CA), subunits of the Na/K-ATPase including Atp1a1, Atp1b1 and Fxyd1 at CP. The estrous cycle stage metestrus (MET) and estrous (ES) were determined before euthanasia. Serum and CP were collected and subjected to RT-qPCR analysis and western blots. Serum was used to measure steroid levels using liquid chromatography tandem mass spectrometry (LC-MS/MS).
RESULTS
Significant differences in gene expression and steroid levels between males and ES females were found, while no differences were found between male and MET females. During ES, expression of Aqp1 was lower (p < 0.01) and NKCC1 was higher in females compared to males. CAII was lower while CAIII was higher in ES females (p < 0.0001). Gene expression of Atp1a1 was lower in ES compared to male (p = 0.0008). Several of these choroidal genes were also significantly different in MET compared to females in ES. Differences in gene expression during the estrus cycle were correlated to serum level of steroid hormones. Protein expression of AQP1 (p = 0.008) and CAII (p = 0.035) was reduced in ES females compared to males.
CONCLUSIONS
This study demonstrates for the first time that expression at CP is sex-dependent and markedly affected by the estrous cycle in female rats. Further, expression was related to hormone levels in serum. This opens a completely new avenue for steroid regulation of the expression of CSF transporters and the close link to the understanding of CSF disorders such as IIH.
Topics: Rats; Female; Male; Animals; Choroid Plexus; Membrane Proteins; Sex Characteristics; Chromatography, Liquid; Tandem Mass Spectrometry; Steroids
PubMed: 37946101
DOI: 10.1186/s12868-023-00829-w -
Biology of Reproduction Jan 2024The endocrinology regulating ovulation of the desired number of oocytes in the ovarian cycle is well described, particularly in mono-ovulatory species. Less is known...
The endocrinology regulating ovulation of the desired number of oocytes in the ovarian cycle is well described, particularly in mono-ovulatory species. Less is known about the characteristics that make one follicle suitable for ovulation while most other follicles die by atresia. Bromodeoxyuridine (BrdU) injection was used to characterize granulosa cell proliferation rates in developing ovarian follicles in the estrous cycle of mice. This methodology allowed identification of follicle diameters of secondary (80-130 μm), follicle-stimulating hormone (FSH)-sensitive (130-170 μm), FSH-dependent (170-350 μm), and preovulatory (>350 μm) follicles. Few preovulatory-sized follicles were present in the ovaries of mice at estrus, the beginning of the cycle. Progressive increases were seen at metestrus and diestrus, when full accumulation of the preovulatory cohort (~10 follicles) occurred. BrdU pulse-chase studies determined granulosa cell proliferation rates in the 24-48 h before the follicle reached the preovulatory stage. This showed that slow-growing follicles were not able to survive to the preovulatory stage. Mathematical modeling of follicle growth rates determined that the largest follicles at the beginning of the cycle had the greatest chance of becoming preovulatory. However, smaller follicles could enter the preovulatory follicle pool if low numbers of large antral follicles were present at the beginning of the cycle. In this instance, rapidly growing follicles had a clear selection advantage. The developing follicle pool displays heterogeneity in granulosa cell proliferation rates, even among follicles at the same stage of development. This parameter appears to influence whether a follicle can ovulate or become atretic.
Topics: Humans; Female; Mice; Animals; Bromodeoxyuridine; Ovarian Follicle; Ovulation; Ovary; Follicle Stimulating Hormone
PubMed: 37801701
DOI: 10.1093/biolre/ioad134 -
Frontiers in Veterinary Science 2023Norwegian Red has been shown to have high levels of estrus behavior under experimental conditions. However, the estrus behaviors of Norwegian Red cows have not been...
INTRODUCTION
Norwegian Red has been shown to have high levels of estrus behavior under experimental conditions. However, the estrus behaviors of Norwegian Red cows have not been studied under commercial conditions.
METHODS
A herd of 89 Norwegian Red cows housed in free stalls on concrete, slatted floors, were continuously video monitored for 21 days. Ovarian cyclicity was confirmed in a final study sample group ( = 18) using milk progesterone concentrations. All mounting and standing activities were recorded, and the duration of mount estrus, standing estrus and the differences between these; prestand and poststand, were determined. The cycle stages metestrus, diestrus and proestrus were estimated based on the starting time and ending time of mount estrus.
RESULTS
All cows in the final study sample group exhibited the primary estrus sign, 'standing to be mounted' during estrus. Two (11%), eleven (61%) and six (33%) cows exhibited the behavior 'standing to be mounted' during metestrus, diestrus and proestrus, respectively. The number of mounts initiated by individual cows was higher during mount and stand estrus than during the rest of the estrous cycle. This study reports a median duration of mount estrus and stand estrus of 21.0 h (interquartile range (IQR) 15.0 to 27.3) and 14.3 h (IQR 12.0 to 18.8), respectively. The median counts per hour of all mount behaviors were 8.6 (IQR 5.6 to 11.3), 1.51 (IQR 0.3 to 3.8) and 1.7 (IQR 0.8 to 6.0) for standing estrus, prestand and poststand, respectively.
DISCUSSION
This study shows that under commercial conditions the Norwegian Red cow displays a high level of mount and stand activity associated with estrus.
PubMed: 37766860
DOI: 10.3389/fvets.2023.1219001