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The American Journal of Pathology Nov 2022Mitochondrial dysfunction is one of the hallmarks of aging. Changes in sebaceous gland (SG) function and sebum production have been reported during aging. This study...
Mitochondrial dysfunction is one of the hallmarks of aging. Changes in sebaceous gland (SG) function and sebum production have been reported during aging. This study shows the direct effects of mitochondrial dysfunction on SG morphology and function. A mitochondrial DNA (mtDNA) depleter mouse was used as a model for introducing mitochondrial dysfunction in the whole animal. The effects on skin SGs and modified SGs of the eyelid, lip, clitoral, and preputial glands were characterized. The mtDNA depleter mice showed gross morphologic and histopathologic changes in SGs associated with increased infiltration by mast cells, neutrophils, and polarized macrophages. Consistently, there was increased expression of proinflammatory cytokines. The inflammatory changes were associated with abnormal sebocyte accumulation of lipid, defective sebum delivery at the skin surface, and the up-regulation of key lipogenesis-regulating genes and androgen receptor. The mtDNA depleter mice expressed aging-associated senescent marker. Increased sebocyte proliferation and aberrant expression of stem cell markers were observed. These studies provide, for the first time, a causal link between mitochondrial dysfunction and abnormal sebocyte function within sebaceous and modified SGs throughout the whole body of the animal. They suggest that mtDNA depleter mouse may serve as a novel tool to develop targeted therapeutics to address SG disorders in aging humans.
Topics: Humans; Mice; Animals; Sebaceous Glands; Skin; Mitochondria; Aging; DNA, Mitochondrial
PubMed: 35948081
DOI: 10.1016/j.ajpath.2022.07.006 -
Antimicrobial Agents and Chemotherapy Aug 2022Lefamulin, a semisynthetic pleuromutilin antibiotic approved in the United States, Canada, and Europe for intravenous and oral treatment of community-acquired bacterial...
Lefamulin, a semisynthetic pleuromutilin antibiotic approved in the United States, Canada, and Europe for intravenous and oral treatment of community-acquired bacterial pneumonia, is highly active against bacterial pathogens that cause sexually transmitted infections (STIs), including multidrug-resistant strains of Neisseria gonorrhoeae, Chlamydia trachomatis, and Mycoplasma genitalium. This nonclinical study used quantitative whole-body autoradiography (QWBA) and qualitative tape-transfer microautoradiography (MARG) to investigate lefamulin distribution into urogenital tract tissues down to a cellular level in male and female rats. A single intravenous dose (30 mg/kg) of [C]-lefamulin was administered to 3 male and 3 female Sprague-Dawley rats. At 0.5, 6, and 24 h post dose, rats were euthanized and [C]-lefamulin distribution was investigated using QWBA and MARG of sagittal planes. [C]-lefamulin was well distributed throughout the carcasses of male and female rats, with the highest concentrations observed in male bulbourethral gland, urethra, prostate in female clitoral gland, uterus (particularly endometrium), and ovary. In these areas, concentrations were similar to or higher than those observed in the lungs. Concentrations peaked at 0.5 h post dose, remaining detectable in the urogenital tract up to 24 h post dose. [C]-lefamulin in rats showed rapid, homogeneous distribution into urogenital tissues down to a cellular level, with high tissue:blood ratios in tissues relevant to STI treatment. These results, and the potent activity of lefamulin against multidrug-resistant bacteria known to cause STIs, will help inform further assessment of lefamulin, including potential clinical evaluation for treatment of STIs.
Topics: Animals; Anti-Bacterial Agents; Chlamydia trachomatis; Community-Acquired Infections; Diterpenes; Female; Male; Pneumonia; Polycyclic Compounds; Rats; Rats, Sprague-Dawley; Sexually Transmitted Diseases; Thioglycolates; Tissue Distribution
PubMed: 35862748
DOI: 10.1128/aac.00355-22 -
Proceedings. Biological Sciences Dec 2022Female genitalia are conspicuously overlooked in comparison to their male counterparts, limiting our understanding of sexual reproduction across vertebrate lineages....
Female genitalia are conspicuously overlooked in comparison to their male counterparts, limiting our understanding of sexual reproduction across vertebrate lineages. This study is the first complete description of the clitoris (hemiclitores) in female snakes. We describe morphological variation in size and shape ( = 9 species, 4 families) that is potentially comparable to the male intromittent organs in squamate reptiles (hemipenes). Dissection, diffusible iodine contrast-enhanced micro-CT and histology revealed that, unlike lizard hemiclitores, the snake hemiclitores are non-eversible structures. The two individual hemiclitores are separated medially by connective tissue, forming a triangular structure that extends posteriorly. Histology of the hemiclitores in Australian death adders () showed erectile tissue and strands/bundles of nerves, but no spines (as is found in male hemipenes). These histological features suggest the snake hemiclitores have functional significance in mating and definitively show that the hemiclitores are not underdeveloped hemipenes or scent glands, which have been erroneously indicated in other studies. Our discovery supports that hemiclitores have been retained across squamates and provides preliminary evidence of differences in this structure among snake species, which can be used to further understand systematics, reproductive evolution and ecology across squamate reptiles.
Topics: Humans; Animals; Male; Female; Biological Evolution; Australia; Snakes; Lizards; Genitalia, Male; Phylogeny
PubMed: 36515117
DOI: 10.1098/rspb.2022.1702 -
Journal of Occupational Health Jan 2023The purpose of this study was to investigate the carcinogenicity of 2-bromopropane (2-BP) in rats.
OBJECTIVE
The purpose of this study was to investigate the carcinogenicity of 2-bromopropane (2-BP) in rats.
METHODS
Male and female F344 rats were exposed by whole body inhalation to 2-BP vapor at concentrations of 0, 67, 200, and 600 ppm for 6 h/day, 5 days/week for 2 years.
RESULTS
All rats of both sexes exposed to 600 ppm died or became moribund within 85 weeks. Death/moribundity was caused by 2-BP induced tumors. In males, significantly increased tumors were malignant Zymbal's gland tumors; sebaceous adenoma and basal cell carcinoma of the skin/appendage; adenocarcinoma of the small/large intestine; follicular cell adenoma of the thyroid; fibroma of the subcutis, and malignant lymphoma of the lymph node. In addition, an increased trend in tumor incidence was found in the preputial gland, lung, forestomach, pancreas islet, brain, and spleen. In females, significantly increased tumors were adenocarcinoma and fibroadenoma of the mammary gland, squamous cell papilloma of the vagina, and large granular lymphocytic leukemia of the spleen. In addition, an increased trend in tumor incidence was found in Zymbal's gland, the clitoral gland, skin, large intestine, pancreas islet, uterus, and subcutis. Particularly, malignant Zymbal's gland tumors were induced even in males exposed to the lowest concentration, 67 ppm.
CONCLUSION
Two-year inhalation exposure to 2-BP resulted in multi-organ carcinogenicity in rats. Based on sufficient evidence of carcinogenicity in this study, 2-BP has the potential to be a human carcinogen.
Topics: Humans; Mice; Rats; Animals; Male; Female; Rats, Inbred F344; Mice, Inbred Strains; Carcinogenicity Tests; Inhalation Exposure; Adenocarcinoma; Adenoma
PubMed: 36756793
DOI: 10.1002/1348-9585.12388 -
Proceedings of the National Academy of... Jun 2023Chemical communication by females remains poorly understood, with most attention focused on female advertisement of sexual receptivity to males or mother-offspring...
Chemical communication by females remains poorly understood, with most attention focused on female advertisement of sexual receptivity to males or mother-offspring communication. However, in social species, scents are likely to be important for mediating competition and cooperation between females determining individual reproductive success. Here, we explore chemical signaling by female laboratory rats () to test i) whether females target their deployment of scent information differentially according to their sexual receptivity and the genetic identity of both female and male conspecifics signaling in the local environment and ii) whether females are attracted to gain the same or different information from female scents compared to males. Consistent with targeting of scent information to colony members of similar genetic background, female rats increased scent marking in response to scents from females of the same strain. Females also suppressed scent marking in response to male scent from a genetically foreign strain while sexually receptive. Proteomic analysis of female scent deposits revealed a complex protein profile, contributed from several sources but dominated by clitoral gland secretion. In particular, female scent marks contained a series of clitoral-derived hydrolases and proteolytically truncated major urinary proteins (MUPs). Manipulated blends of clitoral secretion and urine from estrus females were strongly attractive to both sexes, while voided urine alone stimulated no interest. Our study reveals that information about female receptive status is shared between females as well as with males, while clitoral secretions containing a complex set of truncated MUPs and other proteins play a key role in female communication.
Topics: Female; Male; Animals; Rats; Odorants; Proteomics; Body Fluids; Genetic Background; Hydrolases; Pheromones
PubMed: 37307448
DOI: 10.1073/pnas.2300794120 -
Fertility and Sterility Apr 2002In women, androgens modulate the physiological function of many reproductive and sexual organs, including the ovaries, uterus, vagina, oviducts, clitoris, and mammary... (Review)
Review
OBJECTIVE
In women, androgens modulate the physiological function of many reproductive and sexual organs, including the ovaries, uterus, vagina, oviducts, clitoris, and mammary gland. In this article, we review the mechanisms of androgen action and discuss new data on the effects of androgens in vaginal and clitoral tissues.
MAIN OUTCOME MEASURE(S)
In this study, we characterized the androgen receptor expression in rabbit vaginal tissues from control and ovariectomized animals treated with or without androgen replacement therapy. We investigated the effects of androgen deprivation and replacement on the expression and activity of nitric oxide synthase and arginase and on vaginal smooth muscle contractility.
RESULT(S)
Androgens enhanced nitric oxide synthase activity and down-regulated arginase activity in proximal vagina. Estrogens down-regulated nitric oxide synthase activity and increased arginase activity in distal vagina. Androgens facilitated vaginal smooth muscle relaxation to electric field stimulation and vasoactive intestinal polypeptide, whereas estrogens attenuated vaginal tissue relaxation to electric field stimulation and to vasoactive intestinal polypeptide.
CONCLUSION(S)
These observations suggest that androgens may play an important role in modulating the physiology of vaginal tissue and contribute to female genital sexual arousal.
Topics: Androgens; Animals; Dihydrotestosterone; Female; Genitalia, Female; Humans; Nandrolone; Nitric Oxide Synthase; Receptors, Androgen; Sexuality
PubMed: 12007897
DOI: 10.1016/s0015-0282(02)02978-3 -
Frontiers in Endocrinology 2021Evidence from animal studies has indicated that neonatal thyroid function is vital for the reproductive development. Anogenital distance (AGD), a sensitive biomarker of...
BACKGROUND
Evidence from animal studies has indicated that neonatal thyroid function is vital for the reproductive development. Anogenital distance (AGD), a sensitive biomarker of the fetal hormonal milieu, can be used to predict adult reproductive disorders. However, few human studies have examined the association between neonatal thyroid function and AGD. We aimed to explore their associations in a birth cohort study.
METHODS
Concentrations of thyroid stimulating hormone (TSH) and thyroid hormones (THs), including total triiodothyronine (TT), total thyroxine (TT), free triiodothyronine (FT), and free thyroxine (FT) were measured in cord plasma in the Shanghai-Minhang Birth Cohort. The offspring AGD (AGD [anus-penis] and AGD [anus-scrotum] for boys and AGD [anus-clitoris] and AGD [anus-fourchette] for girls), body weight and anogenital index (AGI = AGD/weight [mm/kg]) were obtained at each follow-up visit. In total, 344 children (194 boys and 150 girls) with cord plasma concentrations of THs and TSH and at least one AGD measurement at birth and at 6, 12, and 48 months of age were included. Multiple linear regression and generalized estimating equation (GEE) models were used to examine the associations of cord plasma concentrations of THs and TSH with AGI.
RESULTS
Multiple linear regression models showed inverse associations of TT, FT, and FT with female AGI, although statistical significance was only reached at birth, 6 and 48 months of age. These associations were also found in GEE models: higher TT and FT concentrations were associated with lower AGI (TT: β = -0.27, 95% CI: -0.50, -0.03 for middle . lowest tertile; FT: β = -0.38, 95% CI: -0.61, -0.16 for middle and β = -0.30, 95% CI: -0.55, -0.04 for highest . lowest tertile). Besides, girls with the highest tertile of FT concentrations had lower AGI than those with the lowest tertile (the highest . lowest tertile: β = -0.22, 95% CI: -0.36, -0.08). Positive associations between TSH and AGI at birth and at 12 months of age were observed in boys.
CONCLUSIONS
This study provides further evidence on the effects of neonatal thyroid function on reproductive development at an early life stage.
Topics: Anal Canal; Anthropometry; Child, Preschool; Female; Genitalia; Humans; Infant; Infant, Newborn; Male; Thyroid Function Tests; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine
PubMed: 34566898
DOI: 10.3389/fendo.2021.736505 -
Przeglad Menopauzalny = Menopause Review Dec 2020Leiomyosarcoma of the vulva is a rare disease accounting for about 1% of all primary vulvar neoplasia but it is the most common type of vulvar sarcomas. Usually it...
INTRODUCTION
Leiomyosarcoma of the vulva is a rare disease accounting for about 1% of all primary vulvar neoplasia but it is the most common type of vulvar sarcomas. Usually it arises from the smooth muscles, blood vessels, rough ligaments, and erector-pili muscles. No treatment algorithms have been established yet. Tumour excision with clean resection lines is considered sufficient, with radiation therapy applied in certain cases.
CASE REPORT
We report a case of a 73-year old patient in whom the disease was manifested by pain syndrome and rapidly growing mass with irregular margins in the symphysis area and satellite nodules. She underwent extensive local excision followed by radiation therapy.
DISCUSSION
Isolated cases and limited series of LMS cases have been described in literature. Leiomyosarcoma is most commonly localized to the labia majora, the Bartholin gland area, clitoris and labia minora. It most often affected perimenopausal women but in younger and pregnant patients was described. The diagnosis is not always easy and different histological markers has to be used. There are no definitive therapeutic algorithms due to the rarity of the disease. The management is surgical treatment and the entire tumour must be removed with histologically verified clean resection margins, followed by radiation therapy in some cases.
CONCLUSIONS
Vulvar tumours are difficult to distinguish macroscopically. Accurate histological diagnosis allows adequate treatment.
PubMed: 33488330
DOI: 10.5114/pm.2020.101949