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Frontiers in Bioscience (Scholar... Jan 2016The term "uterosomes" was first used to classify extracellular membrane vesicles released into the uterine luminal fluid. These extracellular vesicles (EVs), varying in... (Review)
Review
The term "uterosomes" was first used to classify extracellular membrane vesicles released into the uterine luminal fluid. These extracellular vesicles (EVs), varying in sizes, fit the classification of exosomes and microvesicles on the basis of size, the presence of the CD9 biochemical marker, and lateral orientation of the membrane. Uterosomes appear to be formed by the apocrine pathway, similar to other reproductive EVs. In the murine system, the protein cargo carried by uterosomes includes glycosyl phosphatidylinositol (GPI)-linked and transmembrane proteins and these are hormonally regulated, appearing at high levels during proestrus/estrus and only marginally present at diestrus /metestrus. Uterosomes have been shown to deliver proteins in their cargo to sperm, with a functional impact, and are thought to participate in promoting sperm capacitation. Further studies are warranted, particularly those aimed at identifying the contents of their cargo during the estrus and menstrual cycle and the role they play n sperm maturation.
Topics: Animals; Estrous Cycle; Estrus; Exosomes; Female; Fertilization; Humans; Male; Metestrus; Organelle Biogenesis; Proteins; Reproduction; Sperm Maturation; Spermatozoa; Uterus
PubMed: 26709901
DOI: 10.2741/s451 -
Journal of Dairy Science Jun 1985Animal environment is affected by climatic factors that include temperature, humidity, radiation, and wind. Extremes in climate alter energy transfer between the animal... (Review)
Review
Animal environment is affected by climatic factors that include temperature, humidity, radiation, and wind. Extremes in climate alter energy transfer between the animal and its environment and can affect deleteriously reproduction. Seasonal variation of environment, nutrition, and management alters estrous activity and duration of estrus. Conception rates are reduced under stress of heat and cold. Endocrine functions are altered by climatic extremes. In hyperthermia, adrenal function is reduced, and this may allow the animal to cope with the environment because of the lower calorigenic actions of glucocorticoids. Estrogens are lower during the proestrus to metestrus period of the estrous cycle and during late gestation and appear to manifest their physiological actions through shorter duration of estrus and lower calf birth weights, respectively. Season alters endocrine profiles and influences fertility of males. Spermatogenesis is impaired, and testosterone is lower during early exposure to hyperthermia. Environmental modifications can alleviate stress of heat and cold to some extent. Experimentation using indices of environmental measures is needed to assess interactive effects of environment on reproduction.
Topics: Animals; Cattle; Climate; Endocrine Glands; Estradiol; Estrus; Female; Fertility; Glucocorticoids; Hot Temperature; Humidity; Male; Pregnancy; Progesterone; Reproduction; Seasons; Semen; Stress, Physiological; Temperature
PubMed: 3894448
DOI: 10.3168/jds.S0022-0302(85)80995-4 -
Pharmacology Research & Perspectives Jun 2022Sexual dimorphisms are observed in cannabinoid pharmacology. It is widely reported that female animals are more sensitive to the cataleptic, hypothermic,... (Review)
Review
Sexual dimorphisms are observed in cannabinoid pharmacology. It is widely reported that female animals are more sensitive to the cataleptic, hypothermic, antinociceptive, and anti-locomotive effects of cannabinoid receptor agonists such as CP55,940. Despite awareness of these sex differences, there is little consideration for the pharmacodynamic differences within females. The mouse estrus cycle spans 4-5 days and consists of four sex hormone-mediated phases: proestrus, estrus, metestrus, and diestrus. The endocannabinoid system interacts with female sex hormones including β-estradiol, which may influence receptor expression throughout the estrus cycle. In the current study, sexually mature female C57BL/6 mice in either proestrus or metestrus were administered either 1 mg/kg i.p. of the cannabinoid receptor agonist CP55,940 or vehicle. Mice then underwent the tetrad battery of behavioral assays measuring catalepsy, internal body temperature, thermal nociception, and locomotion. Compared with female mice in metestrus, those in proestrus were more sensitive to the anti-nociceptive effects of CP55,940. A similar trend was observed in CP55,940-induced catalepsy; however, this difference was not significant. As for cannabinoid receptor expression in brain regions underlying antinociception, the spine tissue of proestrus mice that received CP55,940 exhibited increased expression of cannabinoid receptor type 1 relative to treatment-matched mice in metestrus. These results affirm the importance of testing cannabinoid effects in the context of the female estrus cycle.
Topics: Animals; Cannabinoid Receptor Agonists; Cannabinoids; Catalepsy; Estrus; Female; Male; Mice; Mice, Inbred C57BL; Receptors, Cannabinoid
PubMed: 35466560
DOI: 10.1002/prp2.950 -
Behavioral Neuroscience Oct 2022The ability to remember sequences of events is fundamental to episodic memory. While rodent studies have examined sex and estrous cycle in episodic-like spatial memory...
The ability to remember sequences of events is fundamental to episodic memory. While rodent studies have examined sex and estrous cycle in episodic-like spatial memory tasks, little is known about these biological variables in memory for sequences of events that depend on representations of temporal context. We investigated the role of sex and estrous cycle in rats during training and testing stages of a cross-species validated sequence memory task (Jayachandran et al., 2019). Rats were trained on a two four-odor sequence memory task delivered on opposite ends of a linear track. Training occurred in six successive stages starting with learning to poke in a nose-port for ≥ 1.2 s; eventually demonstrating sequence memory by holding their nose in the port ≥ 1 s for in-sequence odors and < 1 s for out-of-sequence odors. Performance was analyzed across sex and estrous cycle (proestrus, estrus, metestrus, and diestrus), the latter being determined by cellular composition of a daily vaginal lavage. We found no evidence of sex differences in asymptotic sequence memory performance, similar to humans performing an analogous task (Reeders et al., 2021). Likewise, no differences in sequence memory performance were found across the estrous cycle. Some caveats are that males acquired out-of-sequence trials faster during training with a 3-odor sequence, but this apparent advantage did not carry over to the 4-odor sequence. Additionally, males had shorter poke times overall which seem consistent with a decreased overall response inhibition because they occurred regardless of sequence demands. Together, these results suggest sex and estrous cycle are not major factors in sequence memory capacities. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
Topics: Animals; Estrous Cycle; Estrus; Female; Humans; Male; Metestrus; Proestrus; Rats; Spatial Memory
PubMed: 35254840
DOI: 10.1037/bne0000508 -
Biology of Reproduction Jul 2021Zearalenone (ZEN), a nonsteroidal estrogenic mycotoxin, is detrimental to female reproduction. Altered chemical biotransformation, depleted primordial follicles and a...
Zearalenone (ZEN), a nonsteroidal estrogenic mycotoxin, is detrimental to female reproduction. Altered chemical biotransformation, depleted primordial follicles and a blunted genotoxicant response have been discovered in obese female ovaries, thus, this study investigated the hypothesis that obesity would enhance ovarian sensitivity to ZEN exposure. Seven-week-old female wild-type nonagouti KK.Cg-a/a mice (lean) and agouti lethal yellow KK.Cg-Ay/J mice (obese) received food and water ad libitum, and either saline or ZEN (40 μg/kg) per os for 15 days. Body and organ weights, and estrous cyclicity were recorded, and ovaries collected posteuthanasia for protein analysis. Body and liver weights were increased (P < 0.05) in the obese mice, but obesity did not affect (P > 0.05) heart, kidney, spleen, uterus, or ovary weight and there was no impact (P > 0.05) of ZEN exposure on body or organ weight in lean or obese mice. Obese mice had shorter proestrus (P < 0.05) and a tendency (P = 0.055) for longer metestrus/diestrus. ZEN exposure in obese mice increased estrus but shortened metestrus/diestrus length. Neither obesity nor ZEN exposure impacted (P > 0.05) circulating progesterone, or ovarian abundance of EPHX1, GSTP1, CYP2E1, ATM, BRCA1, DNMT1, HDAC1, H4K16ac, or H3K9me3. Lean mice exposed to ZEN had a minor increase in γH2AX abundance (P < 0.05). In lean and obese mice, LC-MS/MS identified alterations to proteins involved in chemical metabolism, DNA repair and reproduction. These data identify ZEN-induced adverse ovarian modes of action and suggest that obesity is additive to ZEN-induced ovotoxicity.
Topics: Animals; Estrogens, Non-Steroidal; Female; Mice; Mycotoxins; Ovary; Proteome; Zearalenone
PubMed: 33855340
DOI: 10.1093/biolre/ioab069 -
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 -
Archivum Immunologiae Et Therapiae... Jun 2013Neutrophils are excreted into the vaginal vault at metestrus during the estrous cycle, and this phenomenon has long been used to determine the phase of the estrous... (Review)
Review
Neutrophils are excreted into the vaginal vault at metestrus during the estrous cycle, and this phenomenon has long been used to determine the phase of the estrous cycle. A much smaller number of neutrophils are also detected in the uterus and the ovary. Recently, we provided several lines of evidence supporting the notion that neutrophils infiltrate into the ovary to regulate the estrous cycle by opioid peptides. Upon inflammation, on the other hand, neutrophils infiltrate into the site of infection to suppress pain by opioid peptides. Thus, opioid peptides are key molecules by which neutrophils play a novel role in regulation of the pain and estrous cycle. In both cases, opioid peptides appear to be secreted by neutrophils stimulated with chemokines, such as MIP-2 and KC in mouse, corticotropin-releasing hormone and IL-1.
Topics: Animals; Chemokine CXCL1; Chemokine CXCL2; Corticotropin-Releasing Hormone; Estrous Cycle; Humans; Interleukin-1; Mice; Neutrophil Infiltration; Neutrophils; Opioid Peptides; Pain; Signal Transduction
PubMed: 23400274
DOI: 10.1007/s00005-013-0218-1 -
Reproductive Sciences (Thousand Oaks,... Oct 2022Oviductal extracellular vesicles (OEVs) play an important role in fertilization and embryo development. However, it remains largely unknown whether the size and protein...
Oviductal extracellular vesicles (OEVs) play an important role in fertilization and embryo development. However, it remains largely unknown whether the size and protein cargo of OEVs change during the estrous cycle in mice. This study analyzed the changes in the size distribution and protein cargo of OEVs at four stages of the estrous cycle in mice. The distribution widths of OEVs according to the estrous cycle stage were as follows: proestrus, 20-690 nm in diameter, with two peaks at 50 and 250 nm; estrus, 22-420 nm in diameter, with two peaks at 40 and 200 nm; metestrus, 30-70 nm diameter, with a single peak at 40 nm; and diestrus, 10-26 nm diameter, with a single peak at 20 nm. The estrogen receptor (ER) level in OEVs at the proestrus stage differed significantly from that at estrus (P = 0.013) and diestrus (P = 0.005). The levels of CD9 and Hsc70 fluctuated across the four stages, although with no significant differences. Furthermore, OEVs were observed among the cilia and microvilli of epithelial cells at the proestrus, estrus, and diestrus stages, but not at the metestrus stage. The number of observed OEVs was the highest at the proestrus stage, followed by the estrus, and the diestrus stage. Endosomes were also observed at the estrus and diestrus stages. The change of the OEV size and ER cargo is associated with the estrous cycle in mice. Our findings increase the understanding of the physiological characteristics of OEVs, which may have clinical applications.
Topics: Animals; Estrous Cycle; Extracellular Vesicles; Fallopian Tubes; Female; Humans; Mice; Oviducts; Receptors, Estrogen
PubMed: 35137347
DOI: 10.1007/s43032-022-00862-w -
Scientific Reports Jun 2023Mounting evidence shows sex-related differences in the experience of pain with women suffering more from chronic pain than men. Yet, our understanding of the biological...
Mounting evidence shows sex-related differences in the experience of pain with women suffering more from chronic pain than men. Yet, our understanding of the biological basis underlying those differences remains incomplete. Using an adapted model of formalin-induced chemical/inflammatory pain, we report here that in contrast to male mice, females distinctly display two types of nocifensive responses to formalin, distinguishable by the duration of the interphase. Females in proestrus and in metestrus exhibited respectively a short-lasting and a long-lasting interphase, underscoring the influence of the estrus cycle on the duration of the interphase, rather than the transcriptional content of the dorsal horn of the spinal cord (DHSC). Additionally, deep RNA-sequencing of DHSC showed that formalin-evoked pain was accompanied by a male-preponderant enrichment in genes associated with the immune modulation of pain, revealing an unanticipated contribution of neutrophils. Taking advantage of the male-enriched transcript encoding the neutrophil associated protein Lipocalin 2 (Lcn2) and using flow cytometry, we confirmed that formalin triggered the recruitment of LCN2-expressing neutrophils in the pia mater of spinal meninges, preferentially in males. Our data consolidate the contribution of female estrus cycle to pain perception and provide evidence supporting a sex-specific immune regulation of formalin-evoked pain.
Topics: Female; Male; Humans; Animals; Mice; Spinal Cord; Chronic Pain; Pain Perception; Oncogenes; Formaldehyde
PubMed: 37308519
DOI: 10.1038/s41598-023-36245-7 -
Journal of Visualized Experiments : JoVE Aug 2021The current methodology establishes a reproducible, standardized, and cost-effective approach to monitoring the estrous cycle of female Sprague Dawley (SD) adolescent...
The current methodology establishes a reproducible, standardized, and cost-effective approach to monitoring the estrous cycle of female Sprague Dawley (SD) adolescent rats. This study demonstrates the complexity of hormonal cycles and the broad spectrum of understanding required to construct a reliable and valid monitoring technique. Through an in-depth examination of principal experimental design and procedural elements, this description of the cycle and its fundamental principles provides a framework for further understanding and deconstructs misconceptions for future replication. Along with an outline of the sample collection process employing vaginal lavage, the procedure describes the mechanism of data categorization into the four-stage model of proestrus, estrus, metestrus, and diestrus. These stages are characterized by a new proposed approach, utilizing the 4 categorizing determinants of vaginal fluid condition, cell type(s) present, cell arrangement, and cell quantity at the time of collection. Variations of each stage, favorable and unfavorable samples, the distinction between cyclicity and acyclicity, and graphic depictions of the collected categorizing components are presented alongside effective interpretive and organizational practices of the data. Overall, these tools allow for the publication of quantifiable data ranges for the first time, leading to the standardization of categorization factors upon replication.
Topics: Animals; Estrous Cycle; Female; Humans; Metestrus; Rats; Rats, Sprague-Dawley; Rodentia; Vaginal Douching
PubMed: 34515690
DOI: 10.3791/62884