Reproduction in Animal Models of Lysosomal Storage Diseases: A Scoping Review

Background: Lysosomal storage diseases (LSDs) are caused by a mutation in a specific gene. Enzymatic dysfunction results in a progressive storage of substrates that gradually affects lysosomal, cellular and tissue physiology. Their pathophysiological consequences vary according to the nature of the stored substrate, making LSDs complex and multisystemic diseases. Some LSDs result in near normal life expectancies, and advances in treatments mean that more people reach the age to have children, so considering the effects of LSDs on fertility and the risks associated with having children is of growing importance.Objectives: As there is a lack of clinical studies describing the effect of LSDs on the physiology of reproductivity, we undertook a scoping review of studies using animal models of LSDs focusing on reproductive parameters.Methods: We searched six databases: MEDLINE, LILACS, Scopus, Web of Science, Embase and SciELO, and identified 49 articles that met our inclusion criteria.Results: The majority of the studies used male animal models, and a number reported severe morphological and physiological damage in gametes and gonads in models of sphingolipidoses. Models of other LSDs, such as mucopolysaccharidoses, presented important morphological damage.Conclusion: Many of the models found alterations in reproductive systems. Any signs of subfertility or morphological damage in animal models are important, particularly in rodents which are extremely fertile, and may have implications for individuals with LSDs. We suggest the use of more female animal models to better understand the physiopathology of the diseases, and the use of clinical case studies to further explore the risks of individuals with LSDs having children.

Evaluation the Prevalence of Toxoplasma Gondii between Local Cows, and its Effect to Renal and Liver Function in Salah Adeen

The study was conducted to evaluate the epidemiological of toxoplasma gondii in local cows in Salah Adeen, and its effect to renal and liver function. One hundred twenty six sample of serum were collected from cows n different cows farm in Salah Adeen, include Samarra (60 sample), Al-Mutasim (28 sample), Baled (23 sample) and Aldejil (15 sample), from the period between July 2019 until February 2020. The study include detection of serum anti T. gondii IgG antibody by using ELISA Toxoplasma IgG kit, and also determination of serum liver enzymes activity which include (Transaminases enzymes: aspartate transaminase-AST and alanine transaminase-ALT) and also the concentration of serum total protein-TP, albumin, globulin, urea and creatinine. The results indicate that the total percentage for the prevalence of T.gondii between cows in Saleh Eldean was 51.58%, distributed according to the region (68.33% in Samarra, 50% in Al-Mutasim, 26.08% in Baled and 26.66 in Aldejil). While the total percentage for infection with the parasite according to the gender of animals were 58.33% (28 from 48) in male animal and 47.43% (37from 78) in female animal. The results also showed that the level of TP, Albumin, globulin were significantly higher P≤0.05 in sera of infected animals, and also the activity of liver enzymes (AST and ALT) were significantly higher P≤0.05 in sera of infected animals with T.gondii with no significant difference in the level of urea and creatinine in sera of infected group as compared with non-infected group as control group. From all the above results we can conclude that the prevalence of T. gondii was high among animal under investigation, and this infection may be effect to the physiological function especially liver function.

Donchin and Holmes Emerging Scholar Prize Paper Understanding and Correcting Sex Disparity in Cardiovascular Disease Research: Ethical and Practical Solutions

Cardiovascular disease is the leading cause of death of women in the United States, yet cardiovascular research is disproportionately conducted using male human subjects and male animal models. This article deploys Katrina Hutchison’s (2019) analysis of gender disparity in clinical trials as a moral aggregation problem to address the problem of underrepresentation of women in cardiovascular research. I identify cost concerns, convenience, pregnancy, and negligence as potential reasons for the underrepresentation of women in CVD research. Finally, I suggest that multilevel strategies will be needed to eliminate sex disparity in CVD research and improve patient care.

Abstract P746: Sex Differences in Cognitive and Psychological Outcomes of Stroke: Impact of Diabetes

Diabetes increases risk and severity of post-stroke cognitive impairment (PSCI), a major cause of disability worldwide. While it is known that females suffer more from PSCI, psychological outcomes and underlying reasons are poorly understood. From a preclinical perspective, potential explanations include 1) use of otherwise healthy animals in experimental stroke research without integration of common comorbid diseases like diabetes into the study design, and 2) optimization of most behavioral tests for sensorimotor and cognitive functions using only male animal models. Our hypothesis is that post-stroke outcomes are sex and comorbid disease-dependent. To test this, we validated the Novel Object Recognition (NOR), Y-maze, and Passive Avoidance (PAT) behavioral paradigms in Ctrl and Diabetic (DM) male (M) and female (F) rats pre- and post-stroke (S) via 60 min. middle cerebral artery occlusion (MCAO). We tested the PAT paradigm with a multi-trial method where the animals were habituated to the dark/light chambers without foot shock and then trained in 3 trials where they received foot shock upon entering the dark. We then tested retention following MCAO for their memory of foot shock 2 weeks prior. Multitrial results suggested that there was no difference between groups in learning to associate the dark chamber with the shock, so we revised the multitrial method into a single-trial method for ongoing retention tests to compare the impact of stroke on shock memory recall. PAT revealed (Table 1) disease- and sex-dependent responses to aversive stimulus. NOR revealed that M-DM-S and F-DM-S rats have decreased exploration time, suggesting that they are unmotivated or depressed. Y-maze indicated that males displayed spatial memory recovery, while females remained impaired. In summary, we have observed numerous sex- and disease-dependent post-stroke outcomes with standard behavioral paradigms, causing us to carefully consider how we evaluate preclinical outcomes.

Black Dot Type Capitis Tinea Appreciates Bacterial Foliculitis

Tinea capitis is a superficial fungal infection of the scalp and hair, which is seenpredominantly in children. In adults, it is usually related to immunocompromisedpatients and have an atypical features. In patients with end stage renal disease (ESRD),uremia is associated with immune suppression due to the impact of uremic milieu. Allspecimens of tinea capitis should be examined for microscopy, wood’s lamp andculture. Reported a case of 50–year-old male, animal husbandry, presented with itchypapules, pustules, patch alopecia and a hair loss for 6 months. Dermatologic featuresshowed papules, pustules, patch alopecia and black dot. The patient treated withketoconazole shampoo for 3 weeks without any improvement. He had an ESRD for 2years. Gram stain examination and culture showed no bacteri. Wood’s lampexamination showed no fluorescent. Potassium hydroxide (KOH) 10% from scalpscrapings and KOH 20% from hair showed a fungal elements, which support diagnosisof black dot tinea capitis. The patient treated with griseofulvin tablet 500 mg twice aday for 8 weeks, cetirizine tablet 10 mg once daily and 3x/week of ketoconazoleshampoo 2% showed improvement in clinical features and microscopic evaluation.

Sex-determining genes distinctly regulate courtship capability and target preference via sexually dimorphic neurons

For successful mating, a male animal must execute effective courtship behaviors toward a receptive target sex, which is female. Whether the courtship execution capability and upregulation of courtship toward females are specified through separable sex-determining genetic pathways remains uncharacterized. Here, we found that one of the two Drosophila sex-determining genes, doublesex (dsx), specifies a male-specific neuronal component that serves as an execution mechanism for courtship behavior, whereas fruitless (fru) is required for enhancement of courtship behavior toward females. The dsx-dependent courtship execution mechanism includes a specific subclass within a neuronal cluster that co-express dsx and fru. This cluster contains at least another subclass that is specified cooperatively by both dsx and fru. Although these neuronal populations can also promote aggressive behavior toward male flies, this capacity requires fru-dependent mechanisms. Our results uncover how sex-determining genes specify execution capability and female-specific enhancement of courtship behavior through separable yet cooperative neurogenetic mechanisms.

Pituitary Hyperplasia, Hormonal Changes and Prolactinoma Development in Males Exposed to Estrogens—An Insight From Translational Studies

Estrogen signaling plays an important role in pituitary development and function. In sensitive rat or mice strains of both sexes, estrogen treatments promote lactotropic cell proliferation and induce the formation of pituitary adenomas (dominantly prolactin or growth-hormone-secreting ones). In male patients receiving estrogen, treatment does not necessarily result in pituitary hyperplasia, hyperprolactinemia or adenoma development. In this review, we comprehensively analyze the mechanisms of estrogen action upon their application in male animal models comparing it with available data in human subjects. Sex-specific molecular targets of estrogen action in lactotropic (PRL) cells are highlighted in the context of their proliferative and secretory activity. In addition, putative effects of estradiol on the cellular/tumor microenvironment and the contribution of postnatal pituitary progenitor/stem cells and transdifferentiation processes to prolactinoma development have been analyzed. Finally, estrogen-induced morphological and hormone-secreting changes in pituitary thyrotropic (TSH) and adrenocorticotropic (ACTH) cells are discussed, as well as the putative role of the thyroid and/or glucocorticoid hormones in prolactinoma development, based on the current scarce literature.

Melatonin reverts CGRP expression induced by capsaicin

Introduction: CGRP, a neuropeptide synthetized and released in the central nervous system and potent vasodilator, has been implicated in migraine physiopathology. Because of that, there are CGRP targeted therapies that decrease CGRP levels. Melatonin, a pineal gland secretion, has already proved its analgesic effect. We aimed to study CGRP expression in an animal model comparing capsaicin, CGRP and melatonin. Methods: We used in our study male animal rats and separated them into groups based in the kind of received solution (control group, capsaicin only and melatonin plus capsaicin). It was prepared brain stem slices and measured the CGRP levels in the trigemino nucleus caudalis (TNC). Results: Capsaicin group (N = 5) presented low intensity of GCRP expression and animals that received capsaicin plus melatonin (N = 5) showed high intensity of CGRP expression compared to capsaicin group. Conclusion: Melatonin decreases CGRP in an experimental model in rats induced by capsaicin, reducing its inflammatory action in cerebral vessels.