Female Animals Research Articles

Sex hormone deprivation abolishes sex-specific differences in murine colon inflammation and related lipid mediator production.

Unresolved inflammation, due to unfavorable imbalances between pro-inflammatory and pro-resolving mediators, leads to chronic inflammatory pathologies that are often sex-biased and regulated by sex hormones, including inflammatory bowel disease. Lipid mediators (LM) produced from polyunsaturated fatty acids by various lipoxygenases (LOX) and cyclooxygenases govern all stages of inflammation, i.e., the initiation and progression by pro-inflammatory eicosanoids and its resolution by specialized pro-resolving mediators (SPM). Here, we reveal sex-specific differences in murine experimental colitis with male preponderance, which was abolished by sex hormone deprivation using gonadectomy, and this correlated to the levels of inflammation-relevant mediators in the colon. Oral dextran sodium sulfate administration caused more severe colon inflammation in male CD-1 mice than in female counterparts during the acute phase. Colitis in males yielded higher colonic cytokine/chemokine levels but lower 12-/15-LOX-derived LM including SPM compared to female animals in the resolving phase. Sex hormone deprivation in male mice by orchidectomy ameliorated colitis and impaired pro-inflammatory cytokine/chemokine levels but elevated 12-/15-LOX products including SPM, thus abolishing the observed sex differences. Conversely, ovariectomy impaired the levels of those LM that dominated in females and that were increased in males after gonadectomy. Our findings suggest that male sex hormones promote the development of colitis connected to the biosynthesis of inflammatory cytokines, chemokines, and certain LM, especially pro-resolving 12-/15-LOX products that appear to be suppressed in the male colon due to androgens.

The stimulant cathine from Khat causes tachycardia indirectly in the rat.

Leaves of the Khat plant are widely consumed in the Horn of Africa, Yemen and the Jazan region of Saudi Arabia. I have investigated the mode of cardiovascular and autonomic actions of the stimulant cathine from Khat in terms of direct or indirect adrenergic actions in anaesthetised male and female rats, and in isolated tissues. Male and female rats were anaesthetised with pentobarbitone and changes in diastolic blood pressure and cardioaccelerator responses were examined in vehicle-treated or chemically sympathectomised rats. Cathine produced marked tachycardia and smaller blood pressure responses in vehicle-treated animals, with significant rises in heart rate occurring at cathine (0.1mg/kg). In sympathectomised rats, cardiac actions were greatly attenuated in both male and female animals, with no differences between male and female rats. Although pressor responses to cathine were relatively small, sympathectomy significantly reduced these responses in female, but not male, rats. In rat aorta and spleen, cathine produced almost no direct contractions. It is concluded that cathine acts predominantly indirectly, presumably by the release of noradrenaline, in both male and female rats to produce cardiovascular actions. This may have implications for adverse cardiovascular actions of consumption of the plant Khat, particularly with dried Khat, in which actions of cathine may predominate over those of cathinone.

Increased susceptibility to kainate-induced seizures in a mouse model of tuberous sclerosis complex: Importance of sex and circadian cycle.

Comorbidity of epilepsy and autism in tuberous sclerosis complex 2 (TSC2) is very frequent, but the link between these conditions is still poorly understood. To study neurological problems related to autism, the scientific community has been using an animal model of TSC2, Tsc2+/- mice. However, it is still unknown whether this model has the propensity to exhibit increased seizure susceptibility. Further, the importance of sex and/or the circadian cycle in this biological process has never been addressed. This research aimed to determine whether male and female Tsc2+/- mice have altered seizure susceptibility at light and dark phases. We assessed seizure susceptibility and progression in a Tsc2+/- mouse model using the chemical convulsant kainic acid (KA), a potent agonist of the AMPA/kainate class of glutamate receptors. Both male and female animals at adult age were evaluated during non-active and active periods. Seizure severity was determined by integrating individual scores per mouse according to a modified Racine scale. Locomotor behavior was monitored during control and after KA administration. We found increased seizure susceptibility in Tsc2+/- mice with a significant influence of sex and circadian cycle on seizure onset, progression, and behavioral outcomes. While, compared to controls, Tsc2+/- males overall exhibited higher susceptibility independently of circadian cycle, Tsc2+/- females were more susceptible during the dark and post-ovulatory phase. Interestingly, sexual dimorphisms related to KA susceptibility were always reported during light phase independently of the genetic background, with females being the most vulnerable. The enhanced susceptibility in the Tsc2 mouse model suggests that other neurological alterations, beside brain lesions, may be involved in seizure occurrence for TSC. Importantly, our work highlighted the importance of considering biological sex and circadian cycle for further studies of TSC-related epilepsy research. Tuberous sclerosis complex (TSC) is a rare genetic disorder. It causes brain lesions and is linked to epilepsy, intellectual disability, and autism. We wanted to investigate epilepsy in this model. We found that these mice have more induced seizures than control animals. Our results show that these mice can be used in future epilepsy research for this disorder. We also found that sex and time of day can influence the results. This must be considered in this type of research.

The dual amylin and calcitonin receptor agonist KBP-336 elicits a unique combination of weight loss, antinociception and bone protection – a novel disease-modifying osteoarthritis drug

BackgroundDespite the extensive research to provide a disease-modifying osteoarthritis drug (DMOAD), there is still no approved DMOAD. Dual amylin and calcitonin receptor agonists (DACRA) can provide metabolic benefits along with antinociceptive and potential structural preserving effects. In these studies, we tested a DACRA named KBP-336 on a metabolic model of OA in meniscectomised (MNX) rats.MethodsWe evaluated KBP-336’s effect on pain-like symptoms in Sprague Dawley (SD) rats on high-fat diet (HFD) that underwent meniscectomy using the von Frey test to measure the 50% paw withdrawal threshold (PWT) and analyzed using one-way ANOVA. Short in vivo studies and in vitro cell receptor expression systems were used to illustrate receptor pharmacology.ResultsAfter 30 weeks on HFD, including an 8-week treatment, female MNX animals receiving KBP-336 4.5 nmol/Kg/72 h had lower body weight and smaller adipose tissues than their vehicle-treated counterparts. After 20 weeks on HFD, including an 8-week treatment, male rats receiving KBP-336 had lower body weight than the vehicle group. In both the female and male rats, the MNX groups on KBP-336 treatment had a higher PWT than the vehicle-treated MNX group. Aiming to identify the receptor influencing pain alleviation, KBP-336 was compared to the long-acting human calcitonin (hCTA). Single-dose studies on 12-week-old male rats showed that hCTA lowers CTX-I without affecting food intake, confirming its calcitonin receptor selectivity. On the metabolic OA model with 18 weeks of HFD, including 6-week treatment, hCTA at 100 nmol/Kg/24 h and KBP-336 at 0.5, 1.5, and 4.5 nmol/Kg/72 h produced significantly higher PWT in MNX animals compared to MNX animals on vehicle treatment. hCTA and KBP-336 at 0.5 nmol/Kg did not affect body weight and fat tissues.ConclusionOverall, KBP-336 improved the pain observed in the metabolic OA model. Calcitonin receptor activation proved to be essential in this antinociceptive effect.

Molecular and serological prevalence of Leptospira spp. among slaughtered cattle and associated risk factors in the Bahr El Ghazal region of South Sudan

IntroductionLeptospirosis is a neglected emerging and zoonotic disease reported worldwide. This study sought to determine the molecular and serological prevalence of Leptospira spp. and the associated risk factors in slaughtered cattle from the Bahr El Ghazal region of South Sudan.Materials and methodsBetween January 16th and February 25th, 2023, blood and urine samples were collected from 402 cattle at the Lokoloko Municipal Slaughterhouse in Western Bahr El-Ghazal State. Serum samples were tested using the microscopic agglutination test (MAT), with a panel of 12 serovars (sv) from 12 serogroups (sg) and 4 species (spp) of Leptospira spp. These serovars had been previously identified in Sudan and the East African region. Simultaneously, 400 corresponding urine samples were screened using qualitative real-time polymerase chain reaction (PCR) to detect the shedding of Leptospira spp. in urine. To identify the associated risk factors, the age, sex, breed and body condition score of each sampled cattle was noted at the time of sampling and subsequently analysed using logistic regression models.ResultsAmong the 402 serum samples screened, a substantial 81.8% (329/402, 95% CI 77.9–85.3) displayed seropositivity for Leptospira spp. with a MAT titre ≥ 100. The prevalence of urine shedding determined by PCR was 6% (23/400, 95% CI 3.8–8.4), while probable recent leptospirosis with a MAT ≥ 1:800 was observed in 33.1% (133/402, 95% CI 28.6–37.8) of the cattle. Multiple reactions were detected in 34.8% (140/402, 95% CI 30.6–39.5) serum samples. The seropositivity was against L. borgpetersenii sg. Tarassovi (78.6%; 316/402, 95% CI 74.4–82.3), followed by L. borgpetersenii sg. Ballum at 20.4% (82/402, 95% CI, 16.7–24.4%), L. kirschneri sg. Autumnalis At 8.7% (35/402, 95% CI 5.7–11.7), L. interrogans sg. of Pomona at 7.0% (28/402, 95% CI 4.5–9.5), and L. interrogans sg. Hebdomadis was 5.0% (20/402, 95% CI 2.8–7.2). Several risk factors are associated with seropositivity. Older animals (≥ 2 years) had 2.0 times greater odds (95% CI 1.14–3.5) of being seropositive than younger animals (< 2 years), P-value = 0.016. Female animals demonstrated 2.1 times greater odds (95% CI 1.2–3.6) of seropositivity than males did (P-value = 0.008). Additionally, Felata/Mbororo cattle exhibited 2.4 times greater odds (95% CI 1.3–4.5) of being seropositive than did local Nilotic cattle (P-value = 0.005). The agreement between the MAT and PCR results was poor, as indicated by a kappa statistic value of 0.001 and a P-value of 0.913. But there was a moderate agreement between MAT high titres ≥ 800 and PCR positivity with a kappa statistic value = 0.501 and a P-value < 0.001.ConclusionIn addition to the high seroprevalence, Leptospira spp. were found in the urine of slaughtered cattle, suggesting that leptospirosis is endemic to the study area. This finding underscores the significance of cattle as potential sources of infection for slaughterhouse workers, the general public, and other animal species. To address this issue effectively in the Bahr El Ghazal Region and South Sudan, a comprehensive strategy involving a multidisciplinary approach is essential to minimize disease among animals, hence reducing potential zoonotic risks to humans.

Aging is associated with sex-specific alteration in the expression of genes encoding for neuroestradiol synthesis and signaling proteins in the mouse trigeminal somatosensory input

Pain perception is influenced by sex and aging, with previous studies indicating the involvement of aromatase, the estradiol synthase enzyme, in regulating pain perception. Previous research has established the presence of aromatase in dorsal root ganglia sensory neurons and its role in modulating pain perception. The present study aims to explore the implications of aging and sex on the expression of aromatase and estrogen receptors in the trigeminal ganglion. The study examined mRNA levels of aromatase, ERs, and the androgen receptor (AR) in the trigeminal ganglion of 3-month-old and 27-month-old male and female mice, as well as 3-month-old mice from the four-core genotype (FCG) transgenic model. The latter facilitates the assessment of gonadal hormone and sex chromosome implications for sex-specific traits. Aromatase localization in the ganglion was further assessed through immunohistochemistry. Aromatase immunoreactivity was observed for the first time in sensory neurons within the trigeminal ganglion. Trigeminal ganglion gene expressions were detected for aromatase, ERs, and AR in both sexes. Aromatase, ERβ, and GPER gene expressions were higher in young males versus young females. Analyses of the FCG model indicated that sex differences depended solely on gonadal sex. The aging process induced an enhancement in the expression of aromatase, ERs, and AR genes across both sexes, culminating in a reversal of the previously observed gender-based differences. the potential impact of estrogen synthesis and signaling in the trigeminal ganglion on age and sex differences warrants consideration, particularly in relation to trigeminal sensory functions and pain perception.Graphical abstractAge and gonadal sex influence ERs, AR, and ARO levels in the trigeminal ganglion. Although somatosensory perception shows a decline in the elderly, the incidence of trigeminal neuralgia intensifies in aged adults and is predominantly prevalent in women relative to men. The increased expression of aromatase and estrogen receptors in aged female animals suggests that the modulatory influence that neuroestradiol exerts over the trigeminal somatosensory input, inclusive of pain, undergoes changes in elderly male and female individuals in a sex-specific manner.

Neuroprotection or Sex Bias: A Protective Response to Traumatic Brain Injury in the Females

Traumatic brain injury (TBI) is a major healthcare problem and a common cause of mortality and morbidity. Clinical and preclinical research suggests sex-related differences in short- and long-term outcomes following TBI; however, males have been the main focus of TBI research. Females show a protective response against TBI. Female animals in preclinical studies and women in clinical trials have shown comparatively better outcomes against mild, moderate, or severe TBI. This reflects a favorable protective nature of the females compared to the males, primarily attributed to various protective mechanisms that provide better prognosis and recovery in the females after TBI. Understanding the sex difference in the TBI pathophysiology and the underlying mechanisms remains an elusive goal. In this review, we provide insights into various mechanisms related to the anatomical, physiological, hormonal, enzymatic, inflammatory, oxidative, genetic, or mitochondrial basis that support the protective nature of females compared to males. Furthermore, we sought to outline the evidence of multiple biomarkers that are highly potential in the investigation of TBI's prognosis, pathophysiology, and treatment and which can serve as objective measures and novel targets for individualized therapeutic interventions in TBI treatment. Implementations from this review are important for the understanding of the effect of sex on TBI outcomes and possible mechanisms behind the favorable response in females. It also emphasizes the critical need to include females as a biological variable and in sufficient numbers in future TBI studies.

Nonclinical pharmacokinetics of E3112, a recombinant human hepatocyte growth factor, in rats and monkeys by a simple ELISA kit assay

E3112 is a recombinant human hepatocyte growth factor which is under development for the treatment of acute liver failure. Pharmacokinetics (PK) evaluation in experimental animals is important and thus a simple assay for the determination of E3112 in rat and monkey serum has been validated using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. E3112 in rat and monkey serum was quantifiable from 0.313 ng/mL to 15.0 ng/mL without prozone effects. Dilution integrity enabled accurate assay up to 500,000-fold dilution. Accuracy and precision were within the acceptance criteria. PK of E3112 was investigated after intravenous administration to rats and monkeys. PK of E3112 was similar between male and female animals in both species. Nonlinear PK of E3112 was observed in rats after intravenous bolus dose at 1–100 mg/kg while nonlinear PK was not significant in monkeys after intravenous infusion at 0.5–25 mg/kg. These findings suggest that the assay of E3112 in serum using a commercially available ELISA kit was validated and successfully applied to PK studies in rats and monkeys.

Public health importance of brucellosis: a review

Members of the genus Brucella are the source of the infectious bacterial disease known as brucellosis which is characterised by abortion, retained fetal membranes, orchitis, infection of the male accessory sex glands, and decreased fertility. Cattle, pigs, goats, sheep, dogs, camels, and occasionally horses are the animals most commonly affected by the disease. It affects sexually mature animals and its preferred site is the reproductive tract of both male and female animals. Animals may acquire the infection by licking the genitalia of infected female animals shortly after parturition or abortion, or by consuming contaminated pastures, feedstuffs, and water. Because there are insufficient domestic animal health programs, adequate diagnostic facilities, and effective public health measures, brucellosis is common and seen as an important public health concern in developing countries. Due to its association with abortion storm in newly infected herds, a high rate of retained placenta, endometritis or metritis which lowers milk production, and infertility, the disease is important economically. Additionally, the contagious nature of the disease has an impact on public health. In humans, brucellosis is an acute or subacute condition that can last for weeks or months. It is typically characterized by an intermittent or remittent fever, malaise, anorexia, and prostration. Humans can become infected by consuming contaminated animal products such as milk. These and control strategies of brucellosis that include good farm management practices, surveillance, culling of infected animals, use of proper vaccination protocols and public awareness were the subject matter of this review.

Public health importance of brucellosis: a review

Members of the genus Brucella are the source of the infectious bacterial disease known as brucellosis which is characterised by abortion, retained fetal membranes, orchitis, infection of the male accessory sex glands, and decreased fertility. Cattle, pigs, goats, sheep, dogs, camels, and occasionally horses are the animals most commonly affected by the disease. It affects sexually mature animals and its preferred site is the reproductive tract of both male and female animals. Animals may acquire the infection by licking the genitalia of infected female animals shortly after parturition or abortion, or by consuming contaminated pastures, feedstuffs, and water. Because there are insufficient domestic animal health programs, adequate diagnostic facilities, and effective public health measures, brucellosis is common and seen as an important public health concern in developing countries. Due to its association with abortion storm in newly infected herds, a high rate of retained placenta, endometritis or metritis which lowers milk production, and infertility, the disease is important economically. Additionally, the contagious nature of the disease has an impact on public health. In humans, brucellosis is an acute or subacute condition that can last for weeks or months. It is typically characterized by an intermittent or remittent fever, malaise, anorexia, and prostration. Humans can become infected by consuming contaminated animal products such as milk. These and control strategies of brucellosis that include good farm management practices, surveillance, culling of infected animals, use of proper vaccination protocols and public awareness were the subject matter of this review.

Zearalenone modulates the function of goat endometrial cells via the mitochondrial quality control system

AbstractZearalenone (ZEN) is a mycotoxin known for its estrogen‐like effects, which can disrupt the normal physiological function of endometrial cells and potentially lead to abortion in female animals. However, the precise mechanism by which ZEN regulates endometrial function remains unclear. In this study, we found that the binding receptor estrogen receptors for ZEN is extensively expressed across various segments of the uterus and within endometrial cells, and a certain concentration of ZEN treatment reduced the proliferation capacity of goat endometrial epithelial cells (EECs) and endometrial stromal cells (ESCs). Meanwhile, cell cycle analysis revealed that ZEN treatment leaded to cell cycle arrest in goat EECs and ESCs. To explore the underlying mechanism, we investigated the mitochondrial quality control systems and observed that ZEN triggered excessive mitochondrial fission and disturbed the balance of mitochondrial fusion‐fission dynamics, impaired mitochondrial biogenesis, increased mitochondrial unfolded protein response and mitophagy in goat EECs and ESCs. Additionally, ZEN treatment reduced the activities of mitochondrial respiratory chain complexes, heightened the production of hydrogen peroxide and reactive oxygen species, and caused cellular oxidative stress and mitochondrial dysfunction. These results suggest that ZEN has adverse effects on goat endometrium cells by disrupting the mitochondrial quality control system and affecting cell cycle and proliferation. Understanding the underlying molecular pathways involved in ZEN‐induced mitochondrial dysfunction and its consequences on cell function will provide critical insights into the reproductive toxicity of ZEN and contribute to safeguarding the health and wellbeing of animals and humans exposed to this mycotoxin.

METTL14 mediates nerve growth factor-stimulated testosterone synthesis in porcine theca cells†.

Ovarian theca cells produce testosterone, which acts as a vital precursor substance for synthesizing estrogens during follicular development. Nerve growth factor (NGF) has been shown to participate in reproductive physiology, specifically to follicular development and ovulation. There is currently no available data on the impact of NGF on testosterone synthesis in porcine theca cells. Furthermore, m6A modification is the most common internal modification in eukaryotic mRNAs that are closely associated with female gametogenesis, follicle development, ovulation, and other related processes. It is also uncertain whether the three main enzymes associated with m6A, such as Writers, Erasers, and Readers, play a role in this process. The present study, with an in vitro culture model, investigated the effect of NGF on testosterone synthesis in porcine theca cells and the role of Writers-METTL14 in this process. It was found that NGF activates the PI3K/AKT signaling pathway through METTL14, which regulates testosterone synthesis in porcine theca cells. This study will help to further elucidate the mechanisms by which NGF regulates follicular development and provide new therapeutic targets for ovary-related diseases in female animals. Summary Sentence The present study investigated the effect of NGF on testosterone synthesis in porcine theca cells. It was found that NGF activates the PI3K/AKT signaling pathway through METTL14, which regulates testosterone synthesis in porcine theca cells.

Female Animal Characters in Roald Dahl’s Children’s Books: A Misogynistic Portrayal

Children’s literature introduces children to the world, stimulates their imagination, and mirrors the society they live in by reproducing its social rules and accepted norms. This is especially true with gender stereotypes, which display and reinforce the masculine and feminine roles constructed by a given society. This binary, onedimensional, and conventional representation is harmful as it negatively impacts young readers’ apprehension of gender roles as well as their personality, behaviour, and aspirations for the future. World-renowned children’s author Roald Dahl has recently been criticised as a controversial author and a racist, misogynistic person. By adopting a feminist literary critical approach, this study analyses Dahl and his illustrator Quentin Blake’s portrayal of female anthropomorphic characters, generally neglected by previous researchers in favour of human characters, in four books: James and the Giant Peach (1961), The Magic Finger (1966), Fantastic Mr Fox (1970), and The Giraffe and the Pelly and Me (1985). Female characters are weak, inactive, confined indoors, and constantly belittled by their male counterparts who are portrayed as adventurous and as decision makers. Therefore, this study aims to encourage parents and educators to teach young learners to read children’s books with a critical eye to identify and interpret different stereotypical representations.

Expression and localization of anti-Müllerian hormone and its receptors in bovine corpus luteum

Although anti-Müllerian hormone (AMH) is involved in the regulation of granulosa cell function in female animals, its role in tissues other than ovarian follicles remains poorly understood. It has also been suggested that cows with high circulating AMH concentrations have increased fertility; however, the mechanism has not been elucidated. This study was conducted to identify the presence of the AMH-signaling system and its target cells in the bovine corpus luteum formed from an ovulated follicle. Immunoblotting revealed that the proteolytically cleaved C-terminal region in AMH (AMHC), a biologically active peptide, was present in trace amounts in the early corpus luteum and significantly increased during the mid to regressed stages. AMHC and cleaved N-terminal region (AMHN) in AMH generate a noncovalent isoform that improves the activity of AMH signaling. An immunohistochemical analysis revealed that AMHC, AMHN, and type II AMH receptor (AMHR2) were localized to luteal cells during the entire estrous cycle. AMH in the corpus luteum seemed to be newly synthesized since AMH expression was detected. These findings suggest that AMH signaling is involved in the regulation of luteal cell function through an autocrine and post-translational processing mechanism. The level of AMHR2 and mRNA expression of AMHR2 and type I AMH receptors (activin-like kinase 2, 3, and 6) were highest in the mid stage. Thus, AMH signaling in the corpus luteum may also be regulated by changes in the receptor levels. Since the transforming growth factor-beta superfamily, to which AMH belongs, is a multifunctional polypeptide growth factor, further studies are needed to evaluate whether AMH signaling has a role in facilitating or inhibiting luteal cell functions.

Autophagic signaling promotes systems-wide remodeling in skeletal muscle upon oncometabolic stress by D2-HG

ObjectivesCachexia is a metabolic disorder and comorbidity with cancer and heart failure. The syndrome impacts more than thirty million people worldwide, accounting for 20% of all cancer deaths. In acute myeloid leukemia, somatic mutations of the metabolic enzyme isocitrate dehydrogenase 1 and 2 cause the production of the oncometabolite D2-hydroxyglutarate (D2-HG). Increased production of D2-HG is associated with heart and skeletal muscle atrophy, but the mechanistic links between metabolic and proteomic remodeling remain poorly understood. Therefore, we assessed how oncometabolic stress by D2-HG activates autophagy and drives skeletal muscle loss. MethodsWe quantified genomic, metabolomic, and proteomic changes in cultured skeletal muscle cells and mouse models of IDH-mutant leukemia using RNA sequencing, mass spectrometry, and computational modeling. ResultsD2-HG impairs NADH redox homeostasis in myotubes. Increased NAD+ levels drive activation of nuclear deacetylase Sirt1, which causes deacetylation and activation of LC3, a key regulator of autophagy. Using LC3 mutants, we confirm that deacetylation of LC3 by Sirt1 shifts its distribution from the nucleus into the cytosol, where it can undergo lipidation at pre-autophagic membranes. Sirt1 silencing or p300 overexpression attenuated autophagy activation in myotubes. In vivo, we identified increased muscle atrophy and reduced grip strength in response to D2-HG in male vs. female mice. In male mice, glycolytic intermediates accumulated, and protein expression of oxidative phosphorylation machinery was reduced. In contrast, female animals upregulated the same proteins, attenuating the phenotype in vivo. Network modeling and machine learning algorithms allowed us to identify candidate proteins essential for regulating oncometabolic adaptation in mouse skeletal muscle. ConclusionsOur multi-omics approach exposes new metabolic vulnerabilities in response to D2-HG in skeletal muscle and provides a conceptual framework for identifying therapeutic targets in cachexia.

Fig seed oil improves intestinal damage caused by 5‐FU‐induced mucositis in rats

AbstractIntestinal mucositis poses a significant concern associated with cancer therapy. This study aims to investigate the protective and/or healing effect of fig seed oil (FSO) on 5‐fluorouracil (5‐FU)‐induced intestinal mucositis by targeting inflammatory markers and histologic changes in rats. Albino Wistar adult rats were randomly divided into four groups, including three male and three female animals. All the animals in the four groups had a normal standard diet and water throughout the experimental period, which lasted up to 11 days. Rats were administered FSO 0.6 mL (mucositis FSO group) and FSO 0.2 mL (mucositis FSO‐R group) daily throughout the experiment. These two groups and one additional group (mucositis group) were given an intraperitoneal injection of 5‐FU (300 mg/kg) on Day 5 of the experiment. In contrast, the fourth group (Control group) was given an intraperitoneal saline injection on Day 5 of the experiment. FSO treatment ameliorated 5‐FU‐induced intestinal mucositis. On immunohistologic examination, FSO suppressed significantly the activation of NF‐κB and expression of IL‐β and TNF‐α of the harvested intestinal tissue. The reduced dose FSO (mucositis FSO‐R) was as effective as the full dose (mucositis FSO) in suppressing IL‐β and TNF‐α production, but was not as effective as the full dose in suppressing NF‐κB. On light microscopy, FSO attenuated significantly 5‐FU‐induced anomalies, such as the reduction of intestinal villus length and Goblet cell count. The reduced dose FSO (mucositis FSO‐R) was as effective as the full dose (mucositis FSO) in restoring villus length, but was not as effective as the full dose in restoring Goblet cell count. The findings of the study suggest that FSO inhibits 5‐FU‐induced intestinal mucositis via modulation of mucosal inflammation.

Allogenic Follicular Fosterage Technology: Problems, Progress and Potential.

The allogeneic follicular fosterage (AFF) technique transfers cumulus-oocyte complexes (COCs) from pubertal female animals to the dominant follicles of adult female animals for further development, allowing the COCs to further develop in a completely in vivo environment. This article reviews the history of AFF and JIVET and their effects on oocyte and embryo development as well as freezing resistance. Improving the efficiency and reproducibility of AFF technology is crucial to its clinical application. This article discusses factors that affect the success rate of AFF, including differences in specific technical procedures and differences between pubertal and adult follicles. Designing standardized procedures and details to improve the synchronization of donor COCs and recipient follicle maturity and reducing the damage to COCs caused by follicular aspiration may be the direction for improving the success rate of AFF in the future.

Individual differences in the boldness of female zebrafish are associated with alterations in serotonin function.

One of the most prevalent axes of behavioral variation in both humans and animals is risk taking, where individuals that are more willing to take risk are characterized as bold while those that are more reserved are regarded as shy. Brain monoamines (i.e. serotonin, dopamine and noradrenaline) have been found to play a role in a variety of behaviors related to risk taking. Using zebrafish, we investigated whether there was a relationship between monoamine function and boldness behavior during exploration of a novel tank. We found a correlation between serotonin metabolism (5-HIAA:5-HT ratio) and boldness during the initial exposure to the tank in female animals. The DOPAC:DA ratio correlated with boldness behavior on the third day in male fish. There was no relationship between boldness and noradrenaline. To probe differences in serotonergic function in bold and shy fish, we administered a selective serotonin reuptake inhibitor, escitalopram, and assessed exploratory behavior. We found that escitalopram had opposing effects on thigmotaxis in bold and shy female animals: the drug caused bold fish to spend more time near the center of the tank and shy fish spent more time near the periphery. Taken together, our findings indicate that variation in serotonergic function has sex-specific contributions to individual differences in risk-taking behavior.

The Incidence and Severity of Medication Related Osteonecrosis of the Jaws is Similar in Male and Female Mice

Medication related osteonecrosis of the jaws (MRONJ), a rare side-effect of antiresorptive medications, is described as exposed bone in the oral cavity that lasts for at least 8weeks. Most studies report a female predilection for MRONJ; these findings could be due to the increased use of antiresorptives in females, or due to inherent differences between male versus female patients. The purpose of this study was to measure and compare the incidence and severity of osteonecrosis of the jaws (ONJ) between male and female mice. We designed a randomized in-vivo animal study utilizing male and female mice treated with zoledronic acid (ZA). Experimental periodontitis was induced in 24 male and 24 female mice using a silk ligature following administration of saline or a potent bisphosphonate. After 8weeks, animals were evaluated radiographically and histologically. The independent variables were sex (male vs female) and treatment group (ZA vs saline control). Treatment was randomly assigned with balanced distribution between male and female animals. The main outcome variable was ONJ status coded as present or absent. ONJ was defined as present if there was histologic contact between the ligature and the alveolar bone. Secondary outcomes of interest were radiographic and histologic parameters. Statistical differences were analyzed using a two-way analysis of variance with Tukey's post hoc test using a P value of 0.05 for significance. The final sample was composed of 24 vehicle treated and 24ZA treated animals. In vehicle treated animals, 8% of female and 8% of male animals developed ONJ. In ZA treated animals, 83% of female and 92% of male animals developed ONJ. Sex was not associated with the risk (measured as incidence of disease) for developing ONJ or in the radiographic or histologic parameters that were assessed (P values >.1). Sex does not appear to affect the incidence of MRONJ or the severity of the disease as assessed by the radiographic and histologic parameters.

Coevolution of longevity and female germline maintenance.

An often-overlooked aspect of life-history optimization is the allocation of resources to protect the germline and secure safe transmission of genetic information. While failure to do so renders significant fitness consequences in future generations, germline maintenance comes with substantial costs. Thus, germline allocation should trade off with other life-history decisions and be optimized in accordance with an organism's reproductive schedule. Here, we tested this hypothesis by studying germline maintenance in lines of seed beetle, selected for early (E) or late (L) reproduction for 350 and 240 generations, respectively. Female animals provide maintenance and screening of male gametes in their reproductive tract and oocytes. Here, we reveal the ability of young and aged E- and L-females to provide this form of germline maintenance by mating them to males with ejaculates with artificially elevated levels of protein and DNA damage. We find that germline maintenance in E-females peaks at young age and then declines, while the opposite is true for L-females, in accordance with the age of reproduction in the respective regime. These findings identify the central role of allocation to secure germline integrity in life-history evolution and highlight how females can play a crucial role in mitigating the effects of male germline decisions on mutation rate and offspring quality.