Degeneration Of Follicles Research Articles

Multidrug Resistance of Gallibacterium anatis Biovar Haemolytica Isolated from the Reproductive Tracts of Laying Hens.

Antimicrobial resistance is recognized worldwide as one of the greatest threats to human and animal health and the environment. To evaluate the resistance rate of Gallibacterium anatis biovar haemolytica, which contributes to bacteremia, oophoritis, ovarian follicle degeneration, salpingitis, decreased egg production, and increased mortality in hens, strains isolated from the reproductive tracts of layers were analyzed. The oviducts were taken from three hens from each of 10 flocks manifesting clinical signs related to laying. Twenty-two isolates of G. anatis biovar haemolytica collected from the three parts of the reproductive system were identified using MALDI-TOF and molecular methods. The biovar's resistance to 19 antimicrobial substances was assessed using the disk diffusion (n = 8) and broth microdilution (n = 11) methods. The presence of virulence (gtxA, gyrB, and flfA) and antibiotic resistance (blaROB, aphA, tetB, and tetH) genes was examined using PCR. All the isolates were resistant to four or more classes of antibiotics and were considered multidrug-resistant. All such isolates were resistant to tilmicosin, tylosin, and enrofloxacin, 88.2% were to tetracycline, and 82.4% to vancomycin. The gtxA, gyrB, tetB, and tetH genes were demonstrated. Considering the present prevalence of multidrug resistance among G. anatis biovar haemolytica isolates from laying hen reproductive tracts, surveillance in reproductive flocks is warranted.

ThP2.15 - Investigating the use of autologous stem cell therapy in the treatment of Androgenetic Alopecia

Abstract Background and Introduction Androgenetic alopecia (AGA) is the commonest form of alopecia and is characterised by progressive degeneration of hair follicles and programmed cell death, impacting individuals of both genders. This affects 80% of individuals in the Caucasian population and causes impairment of quality of life. The cause of AGA is complex and involves androgens, genetics, and hormonal miniaturisation. Dihydrotestosterone (DHT) is the primary androgen responsible for activating pathogenic pathways, resulting in the shortening of terminal follicles. Existing treatment methods are currently limited, and the development of a therapeutic approach that overcomes these limits might be of importance in plastic surgery. Method A comprehensive search is conducted on databases including Pubmed, Medline, Ovid, and Embase. Research studies are extracted and analysed using the PRISMA table. Results The bulge region serves as a vital reservoir of epidermal and melanocytic stem cells. The use of Rigenera® and autologous stem cell therapy has the capability to collect and separate these stem cells (SCs), leading to a 29% ± 5% augmentation in hair density over a span of 6 months. Additional types of multipotent stem cells, such as those found in adipose tissue, bone marrow, and human umbilical cord blood, might potentially be suitable for the purpose of hair regeneration. Possible advantages include a reduced number of biopsies, a shorter treatment duration, and not being limited by the number of donor follicles compared to surgical intervention. Conclusion Autologous stem cell therapy demonstrates potential effectiveness and warrants additional investigation to enhance the therapeutic efficacy of AGA.

Ruxolitinib Has a Protective Effect on Ovarian and Endometrial Tissues in Diabetic Rats via STAT3 Pathway

Background: Hyperglycemia is associated with ovarian dysfunction. Advanced glycation end products (AGE) may affect ovarian function by binding to particular AGE receptors (RAGE). Hematopoiesis and immunological conditioning are both controlled by the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. Many JAK-STAT signaling inhibitors, including ruxolitinib, have been approved to treat inflammatory disorders. We aimed to examine the potential protective effect of ruxolitinib, on ovarian dysfunction by comparing biochemical, pro-inflammatory, and histological abnormalities in a diabetic rat model. Methods: 24 female Wistar albino rats were included in the study. Diabetes was induced by streptozotocin (STZ) in 16 rats. Group 1: control (no diabetes mellitus, n = 8), Group 2 (diabetic = 8, 1 mL/kg/day saline, 4 weeks), and Group 3 (diabetic, n = 8, 2 mg/kg/day ruxolitinib, 4 weeks). The animals were euthanized, and bilateral hysterectomy and ovariectomy were performed for histopathological examination. The levels of signal transducer and activator of transcription 3 (STAT3) in tissue supernatants were measured. Results: Endometrial gland, ovarian stromal, and ovarian follicle degeneration scores were higher in group 2 compared with group 3 at p < 0.001, whereas ovarian STAT3 level was significantly higher in group 2 compared with group 3 at p < 0.001. Conclusions: Ruxolitinib can be a promising candidate for providing endometrial and ovarian structure continuity by JAK-STAT inhibition in diabetes.

MERCURY EXPOSURE AND HUMAN REPRODUCTIVE HEALTH (LITERATURE REVIEW)

Mercury (Hg), a highly toxic environmental pollutant, which hazards for human health, including to reproductive system, fertility and pregnancy outcome. Research has shown that Hg could induce impairments in the reproductive function due to cellular deformation of the Leydig cells and the seminiferous tubules, testicular degeneration and degenerative atresia of primordial and primary follicles as well as diminishes the steroidogenesis and synthesis of sex hormones. Some studies investigated miscarriage, spontaneous abortions, stillbirth, and low birth weight due to occupational Hg exposure. This review evaluates the hypothesis that exposure to Hg may. This review evaluates the hypothesis that chronic exposure to mercury can increase the risk of reduced fertility, spontaneous abortion and congenital deficits or abnormalities.

Reduction in reproductive activity from degeneration of testicular follicles in Megapitaria squalida (Mollusca: Bivalvia) exposed to metal pollution in the Gulf of California

Over a reproductive cycle, the prevalence and intensity of degeneration of testicular follicles in Megapitaria squalida collected from the mining port of Santa Rosalia (a highly metal-polluted area), and San Lucas (a less polluted site), Gulf of California, Mexico, were evaluated. At San Lucas, most individuals had a typical testicular structure, and degeneration of testicular follicles was present in 9.5 % of spawning organisms. In contrast, at Santa Rosalia, 68 % of males, mainly in the ripe stage, had testicular degeneration (72 % severe intensity, mostly in medium and large-sized). Degeneration was characterized by intense hemocyte infiltration, identified as dense masses with numerous melanized cells in the follicle lumen. In both sites, males with testicular follicles degeneration had a lower condition index compared to males without degeneration. Degeneration of testicular follicles before spawning compromises and decreases the reproductive activity of M. squalida males at Santa Rosalia, which may ultimately affect the population sustainability.

Vitamin C Synergistically Enhances Protective Effects of Vitamin E Against Preantral Follicle Degeneration of Ovine Vitrified/Warmed Ovarian Tissue.

This study aimed to evaluate whether the addition of vitamins E and C as two conventional antioxidants improves the cryotolerance of preantral follicles enclosed in ovine ovarian tissue slices. For this purpose, ovarian slices were obtained from abattoired juvenile lambs and randomly distributed to the following groups: fresh, toxicity, vitrified (control), and three treatment groups in two experiments. Vitamin E, vitamin C, or vitamin E + C was added to the vitrification media alone in the first experiment and added to all vitrification, warming, and culture media in the second experiment. Finally, the treated tissues were cultured in vitro for 12 hours. The histological analysis showed that single or combined use of vitamins E and C increases intact preantral follicles in comparison to the control in two experiments (p < 0.05), and simultaneous use of vitamins E and C had a synergistic effect on increasing the percentage of normal preantral follicles in experiment 2 (p < 0.05). Due to the better results in Experiment 2, stromal cell density, antioxidant activity, and molecular evaluation were followed only in this experiment. The vitamin E + C group had higher stromal cell density compared with control group (p < 0.05). Vitamin E strengthened antioxidant capacity compared with the control and vitamin C groups (p < 0.05). This effect was exacerbated when used in combination with vitamin C (p < 0.05). The expression of all evaluated genes (BMP4, BMP15, GDF9, and KITLG) was significantly increased in ovarian tissue treated with vitamin E + C compared with the control group (p < 0.05). This increase was also observed in BMP4, GDF9, and KITLG genes compared with the vitamin C group (p < 0.05). In conclusion, this study revealed the positive effects of vitamins E and C on preantral follicle viability and to some extent a synergistic action of vitamin C on the protective effects of vitamin E against preantral follicle degeneration and increasing antioxidant capacity and development of preantral follicles after ovine ovarian tissue vitrification.

Ganoderma lucidum and Hypericum perforatum Exhibit Anti-Inflammatory, Antioxidant, and Anti-Androgen Effect in Rat Model of Experimental Polycystic Ovarian Syndrome

Objective: Chronic inflammation is considered to be of key importance in the pathogenesis of polycystic ovarian syndrome (PCOS). Ganoderma lucidum polysaccharide (GLP) and Hypericum perforatum (HP) have been reported to have anti-inflammatory and antioxidant activities. We studied the effects of these agents on ovarian tissue in a rat model of experimental PCOS. Materials and Methods: Forty-two Sprague-Dawley female rats were divided into 6 groups with 7 animals in each group as listed below: Group 1: Control, Group 2: PCOS, Group 3: PCOS + HP, Group 4: HP only, Group 5: PCOS+ GLP, Group 6: GLP only. At the end of the experimental procedures, all the animals underwent bilateral oophorectomy and blood samples were collected. Ovarian tissue and blood samples were used for biochemical and histopathological analysis. Results: Follicle degeneration in the PCOS group showed a statistically significant increase compared to the other groups (p < 0.05). Cystic follicles were significantly reduced in the PCOS+GLP and PCOS+HP groups as compared to the PCOS group. Levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were elevated in PCOS rats (p < 0.01). Levels of sex hormone binding globulin (SHBG) levels were diminished (p < 0.01). Levels of malondialdehyde (MDA) and insulin-like growth factor 1 (IGF-1) were increased in PCOS rats as compared to the other groups (p < 0.02, p < 0.02, respectively). GLP supplementation diminished the levels of IGF-1 and MDA. GLP or HP supplementation increased reduced glutathione (GSH). Conclusion: GLP and HP treatment normalizes SHBG levels while correcting PCOS-induced hyperandrogenemia. Both herbs regulate the redox balance by decreasing the levels of MDA and increasing the level of GSH.

The histological and hormonal changes that occur on reproductive system and pregnancy in adult albino mice after treatment of tramadol

Tramadol is a centrally active synthetic opioid analgesic that is used extensively. The present research conducted to outline the histological changes on reproductive system ( ovaries and uterus of females and testis of male) and hormonal status of mature albino mice . Fourty mice (male and female) weighing approximately 25-30g were used in the present study. Animals were divided into two groups control male and females (n=20) and tramadol treatment male and female group (n=20). Applied tramadol doses 25mg /Kg/day were daily injected intramuscular for 60 days. At the end of treatment, the animals were sacrificed and their ovary, uterus and testis were incised and fixed in 10% formalin for histological investigation .The blood sample were collected for measure hormonal levels (sex hormones) of both sex. The results of males hormones levels showing highly significant reduce in the level of testosterone and highly significant increase in the level of prolactin hormone while (FSH and LH) showed significant decrease as compared with control group. The result of female hormones levels showed a highly significant reduce in the level of Estradiol and significant decrease in the level of (FSH and LH) hormones as compared with control group. The histological section of ovary showing damage of growing follicles, increase cellularity of stroma, cystic follicle degeneration. There were hypertrophied endometrium glands , atrophic endometrium lining of uterus, testis possessed disorganization of the seminiferous tubules with inflammatory cells, degenerative change in germ cell with vacuolated epithelium.

Revisiting the spawning fraction of Pacific bluefin tuna (Thunnus orientalis) caught in the Sea of Japan based on diurnal changes in spawning markers

The spawning fraction (SF) is an important reproductive trait used to assess the reproductive potential of indeterminate spawning fishes. To estimate the SF more accurately, the durations of spawning markers in ovaries need to be determined. The SF of the Pacific bluefin tuna Thunnus orientalis (PBF) in the Sea of Japan (SOJ) is higher than the SFs in its other main spawning grounds. The present study aimed to revisit the SF of the PBF in the SOJ by focusing on diurnal changes in spawning markers and estimating the duration of spawning markers in PBF ovaries. According to diurnal changes in the postovulatory follicle (POF) degeneration process and final maturation process of oocytes, POFs were observed in ovaries up to 38.5 h after ovulation. The revisited total SF throughout the spawning season was 0.34–0.43 in Area 1 and 0.50–0.64 in Area 2; these values are smaller than the SF previously estimated in the SOJ. The estimated SF of the PBF in the present study was equal to or slightly higher than that in the water between the Nansei Islands, Japan, and the northeast of the Philippines and higher than that in the Kuroshio-Oyashio transition area.

P-429 Transcriptomic heterogeneity within cortical ovarian follicle pool in child and adult

Abstract Study question What are the transcriptomic differences between child and adult ovarian follicles in the human cortex? Summary answer Our results suggest that human ovarian cortical follicles show marked differences before and after puberty, with the greatest differences being present in the secondary stage. What is known already The ovaries and their main functional structures, follicles, are important for determining the reproductive health. Follicle growth and maturation are controlled by multiple mechanisms, including the hypothalamus pituitary ovarian axis and local paracrine signalling. Although dormant primordial follicles are activated to grow even in infancy, all growing follicles before the first menarche are bound to undergo atresia. Follicle growth activation in infancy and adulthood remains poorly understood. Additionally, child and adult follicles behave differently during in vitro culture suggesting differing biology, raising many questions e.g., about their suitability for fertility preservation. Study design, size, duration Ovarian cortical tissues from children were collected through fertility preservation program at the Helsinki Children’s hospital (Finland). Families of underage patients signed an informed written consent. Adult ovarian tissue was collected from gender reassignment patients at the Helsinki University hospital and Karolinska university hospital after informed written consent. Follicles at different maturation stages were isolated from ovarian cortex for single follicle transcriptomic analysis. Freshly-fixed cortical biopsies (3x3x1 mm3) were used for validation of transcriptomic analysis. Participants/materials, setting, methods Single viable follicles (n = 120, 60/age group) were mechanically and enzymatically isolated from frozen-thawed ovarian tissue from four adults (age &amp;gt;18 yrs) and five children (age 1-11 yrs) and processed for RNA-sequencing. Individual follicles were lysed, prepared for RNA libraries following Smart-Seq2 protocol and sequenced using NextSeq 500 platform. After quality assessment, 109 follicles were analysed (Adult n = 54, Child n = 55). DDX4, AMH, FOXL2 and DAZL transcripts and proteins localization were evaluated via immunodetection and RNA-FISH assay. Main results and the role of chance Principal component analysis (PCA) of all sequenced follicles demonstrated an expected timely progression of their stages based on maturation, and an overall similarity between child and adult. Interestingly, PCA displayed two distinct clusters of follicles in both adult and child samples. The first group contained only growing follicles and, after differentially expressed gene (DEG) analysis, demonstrated lower expression of traditional oocyte markers (group 1). The second group consisted of primordial and growing follicles and had lower expression of traditional granulosa marker (group 2). Group-related differential expression of main oocyte (DDX4, DAZL) and granulosa (FOXL2, AMH) marker genes were validated in tissue sections with RNA-FISH. Downstream analyses focused on group 2 follicles. When child and adult follicles were compared to each other, the highest number of DEGs were found in the secondary stage (primordial n = 32, primary n = 14, secondary n = 387). Pathway analysis of DEG displays enrichment of oestrogen-related related pathways in adult secondary follicles. Furthermore, we analysed DEGs between the follicular stages per age group, finding high number of DEGs between primordial and primary follicles (Adult n = 1663, Child n = 1914). The majority of those genes are unique to the age group (common=512). Limitations, reasons for caution Adult ovarian tissue is obtained from gender reassignment patients, who receive androgen treatments prior to surgery. Child ovarian tissue was collected from fertility preservation programme where some patients were exposed to chemotherapy prior to tissue collection. Wider implications of the findings The differences between child and adult follicles encourage further investigation of the suitability of child ovarian tissue in current fertility preservation protocols. Understanding transcriptomic changes during early folliculogenesis and reasons for follicle degeneration can help tailor protocols for in vitro growth of follicles. Trial registration number not applicable

Effects of varying doses of conjugated estrogen on body weight, hormonal and histological alterations of reproductive organs in adult swiss albino female mice

Estrogens are a group of hormones that have diverse effects on both reproductive and non-reproductive organs. Conjugated estrogens are medicine that contains a mixture of estrogen hormones. The study was conducted to observe the effects of varying doses of conjugated estrogen on body weight, hormonal and histological alterations of reproductive organs in adult swiss albino female mice. In this study, 60 female swiss albino mice (Mus musculus) aged 28–30 days with an average body weight of 28.2 ± 1 g were used. At first, the mice were randomly divided into 4 groups each containing 15 mice. Group A was served as vehicle control and fed on standard mice pellet and fresh drinking water. While, groups B, C and D were administered with conjugated estrogen orally at the daily dose rate of 125 μg, 250 μg and 500 μg/kg body weight respectively with 1 mL sesame oil as a vehicle by mixing with feed. The experiment was carried out for 90 days. After humanly euthanized, blood was collected and serum was prepared and organs were collected for histopathology. The results revealed that higher doses of conjugated estrogen resulted in weight loss in premenopausal female mice compared to lower doses. Serum estrogen and thyroxine concentration was increased significantly following the doses of conjugated estrogen. Ovarian histotexture showed congested blood vessels and cystic space with degeneration of follicles and corpus luteum. Uterine lesions included massive macrophage infiltration in endometrium and hyperplasia of glandular epithelium at a lower dose; hyperplasia and hypertrophy of glandular epithelium (pleomorphism) with normal macrophage infiltration in endometrium at a higher dose. Therefore, it can be concluded that oral conjugated estrogen therapy at high dose has more detrimental impacts on body weight and reproductive function compared to lower dose in female adult mice.

The protective effects of astaxanthin on pre-antral follicle degeneration in ovine vitrified/warmed ovarian tissue

This study assesses the protective effects of astaxanthin (AST) against vitrification/warming-induced cryoinjuries of ovarian tissue slices in sheep. Cortical slices of slaughterhouse acquired-ovine ovaries were randomly distributed in different groups: fresh, toxicity, and five vitrification groups including vitrification in presence of 0 (control group), 1, 10 and 100 μM astaxanthin or 100 μM vitamin E. After vitrification/warming and 24 h culturing, the samples were subjected to histological studies, antioxidant evaluation by TAC and TBAR assays, and assessment of relative expression of BMP4, BMP15, GDF9 and KITLG genes related to folliculogenesis and follicular growth regulation. According to the results, vitrification reduced the percentage of morphologically intact follicles compared to the fresh and toxicity groups (p < 0.05). In vitrification groups, vitamin E and all three concentrations of AST increased the percentage of intact pre-antral follicles and antioxidant activity relative to the vitrified control (p < 0.05). This enhancement significantly occurred in 10 μM AST group more than vitamin E (p < 0.05). Also, 10 μM concentration of AST enhanced the expression of all the examined genes compared to the control (p < 0.05), while the expression of BMP4, BMP15 and KITLG was higher in the AST than vitamin E (p < 0.05). The latter could increase only the expression of GDF9 compared to the control group (p = 0.011). In conclusion, AST is a highly effective antioxidant for maintaining the survival of pre-antral follicles, retaining cell density, increasing total antioxidant capacity, and increasing the expression of some genes related to follicular development after short-term culture of vitrified/warmed ovarian tissue slices.

Protective Effect of Adenosine Triphosphate against 5-Fluorouracil-Induced Oxidative Ovarian Damage in vivo.

The aim of our study was to analyze the effect of ATP on possible ovarian damage of 5-FU in rats. The animals were divided to three groups; healthy group (HG), 5-FU alone group (FUG) and ATP+5-FU administered group (AFU). The ATP 4 mg/kg was injected intraperitoneally (IP) into the AFU group. The same volume of saline (0.9% NaCl) as the solvent was administered intraperitoneally to the HG and FUG groups. One hour after administering ATP and solvent, 5-FU 100 mg/kg was injected intraperitoneally to the animals in the AFU and FUG groups. ATP was administered to the animals once a day for 10 days. On the 1st, 3rd and 5th days of 5-FU, one dose (total of 3 doses) was administered. On day 10, the animals were euthanasia with high-dose anaesthesia and ovarian tissues were removed. The removed ovaries were analyzed biochemically andhistopathological. ATP significantly suppressed both the increase in MDA and IL-6 levels, and the decrease in tGSH, SOD and CAT levels. Treatment with ATP significantly suppressed the severe vacuolization and primordial follicle degeneration induced by 5-FU in our study. ATP was possible to be useful for the treatment of 5-FU-induced ovarian damage.

Effect of adenosine triphosphate on ribociclib-induced skin toxicity in rats

Purpose Ribociclib is a CDK4/6 inhibitor approved for the treatment of breast cancer; it inhibits the activity of CDK4/6 by competitively binding to adenosine 5'-triphosphate (ATP) binding sites. Although generally well-tolerated, ribociclib has been connected to a number of serious dermatologic complications. This study explored the effects of ATP on ribociclib-induced skin damage. Materials and methods Using a rat model, ATP 25 mg/kg was injected intraperitoneally in the ATP + Ribociclib (ATR) group (n = 6). Distilled water as solvent was applied to the healthy control (HC) group (n = 6) and ribociclib (RCB) group (n = 6). One hour after ATP and solvent administration, ribociclib (200 mg/kg) suspension prepared in distilled water was administered to the stomach by gavage (ATR and RCB groups). This was repeated once a day for 15 d. After that period, biochemical markers were studied in the skin tissues and histopathological evaluations were conducted. Results In the histopathological evaluation of the RCB group, dermal necrosis, degeneration in hair follicles, and pycnosis in keratinocytes were observed. Only mild degeneration was observed in the ATR group; the HC group had a normal histological appearance. The malondialdehyde (MDA) values were significantly higher and the superoxide dismutase (SOD), catalase (CAT), and total glutathione (tGSH) levels were significantly lower in the RCB group in comparison to the HC group (p < .001). ATP reduced the ribociclib-induced increases in the MDA values and decreased the SOD, CAT, and tGSH levels in the ATR group (p < .001). Conclusion ATP may be useful in the treatment of ribociclib-induced skin damage.

Ivermectin and Allium cepa Protect against Cadmium-Induced Ovarian and Uterine Damage in Adult Wistar Rats

Background: Female reproductive organs are more susceptible to the risk of increased cadmium accumulation. Ivermectin is a known therapeutic drug in general medicine, while Allium cepa possesses antioxidant ability. This study investigated the effects of Ivermectin and Allium cepa on cadmium-induced ovarian and uterine damage in adult Wistar rats. Methodology: Twenty-Eight adult female Wistar rats were randomly divided into six groups. Group (A); control group, Group (B); treated with 1.2 mg/kg b.w of Ivermectin, Group (C); treated with 1.2 mg/kg BW of Ivermectin and 2 mg/kg BW Cadmium respectively, Group (D); treated with 2 mg/kg BW Cadmium, Group (E); treated with 2 mg/kg BW Cadmium and 1.5 ml Allium cepa respectively, and Group (F); treated with 1.5 ml Allium cepa. The administration was done orogastrically and daily for four weeks. Animals were euthanized by cervical dislocation twenty- four hours after the last administration, Ovary and Uterus excised following abdominal incision, tissues for histological observation fixed in Bouins’ fluid for H/E stain, Masson trichrome, fuelgen stain, and toluidine blue stain respectively. Samples for enzymes assay were homogenized in 5% sucrose solution for lipid peroxidation using; MDA and the antioxidant enzymes using SOD and CAT. Result: Cadmium treatment exerted oxidative stress, elevated the enzyme markers for oxidative damage in the ovary and uterus, and increased lipid peroxidation leading to cell membrane damage. Histological alterations, degeneration of ovarian follicles, and loss of endometrial lining characterized the animals exposed to cadmium. Allium cepa increased the antioxidant enzymes; SOD and CAT while lowering the MDA activities in Cadmium-induced oxidative stress. Histological integrity of the ovary and uterus was maintained; follicular development was evident at various stages, and the endometrial lining integrity was maintained. Conclusion: This study demonstrated the protective role of Allium cepa and Ivermectin against cadmium toxicity on the reproductive organs in female adult Wistar rats

Toward Elucidating Epigenetic and Metabolic Regulation of Stem Cell Lineage Plasticity in Skin Aging.

Skin is the largest organ in human body, harboring a plethora of cell types and serving as the organismal barrier. Skin aging such as wrinkling and hair graying is graphically pronounced, and the molecular mechanisms behind these phenotypic manifestations are beginning to unfold. As in many other organs and tissues, epigenetic and metabolic deregulations have emerged as key aging drivers. Particularly in the context of the skin epithelium, the epigenome and metabolome coordinately shape lineage plasticity and orchestrate stem cell function during aging. Our review discusses recent studies that proposed molecular mechanisms that drive the degeneration of hair follicles, a major appendage of the skin. By focusing on skin while comparing it to model organisms and adult stem cells of other tissues, we summarize literature on genotoxic stress, nutritional sensing, metabolic rewiring, mitochondrial activity, and epigenetic regulations of stem cell plasticity. Finally, we speculate about the rejuvenation potential of rate-limiting upstream signals during aging and the dominant role of the tissue microenvironment in dictating aged epithelial stem cell function.

The effect of carvacrol on oxido-inflammatory ovarian injury and infertility induced by ischemia-reperfusion in rats

Background: Increased oxidants and proinflammatory cytokines play a role in the pathogenesis of ovarian ischemia-reperfusion (OIR) injury and related infertility. Carvacrol has antioxidant, antibacterial and anti-inflammatory properties. Methods: Protective effect of carvacrol against ischemia-reperfusion (IR)-related ovarian damage and infertility was investigated. IR process were applied to the ovaries of rats, which were divided into the following groups (n = 12): OIR, IR +50 mg/kg carvacrol (IRC-50), IR +100 mg/kg carvacrol (IRC-100) and sham group (SG). After the reperfusion process, six rats from each group were killed and the removed ovaries were examined biochemically and histopathologically. The remaining animals were kept two months with mature male rats to reproduce. Results: At a dose of 50 mg/kg, carvacrol suppressed the oxidant parameter increase and antioxidant decrease caused by IR in ovarian tissue. At a dose of 100 mg/kg, carvacrol antagonized both oxidant and proinflammatory cytokine increase and antioxidant decrease. Histopathologically, severe degeneration of follicles in the ovaries of the OIR group, necrotic cell accumulations, hemorrhage in the corpus luteum, edema in the interstitial tissue, polymorphous nuclear leukocyte (PNL) infiltration, and congestion and dilation of blood vessels were detected. Inflammatory symptoms such as edema in the ovarian tissue, congested dilated blood vessels and PNL infiltration were observed at a dose of 50 mg/kg of carvacrol, but these histopathological findings were not observed at a dose of 100 mg/kg. Conclusion: A dose of 100 mg/kg carvacrol, which eliminated inflammatory damage, significantly prevented the development of IR-induced infertility. Carvacrol may be beneficial in the treatment of IR-related ovarian damage and infertility.

Warm and cold temperatures have distinct germline stem cell lineage effects during Drosophila oogenesis.

Despite their medical and economic relevance, it remains largely unknown how suboptimal temperatures affect adult insect reproduction. Here, we report an in-depth analysis of how chronic adult exposure to suboptimal temperatures affects oogenesis using the model insect Drosophila melanogaster. In adult females maintained at 18°C (cold) or 29°C (warm), relative to females at the 25°C control temperature, egg production was reduced through distinct cellular mechanisms. Chronic 18°C exposure improved germline stem cell maintenance, survival of early germline cysts and oocyte quality, but reduced follicle growth with no obvious effect on vitellogenesis. By contrast, in females at 29°C, germline stem cell numbers and follicle growth were similar to those at 25°C, while early germline cyst death and degeneration of vitellogenic follicles were markedly increased and oocyte quality plummeted over time. Finally, we also show that these effects are largely independent of diet, male factors or canonical temperature sensors. These findings are relevant not only to cold-blooded organisms, which have limited thermoregulation, but also potentially to warm-blooded organisms, which are susceptible to hypothermia, heatstroke and fever.

Histological and biochemical apoptosis changes of female rats′ ovary by Zinc oxide nanoparticles and potential protective effects of l-arginine: An experimental study

BackgroundThis research aims to investigate the adverse effects of ZnO NP on ovarian tissue and the follicular and menstrual cycle and the protective effects of l-arginine on the aforementioned tissues. Material and methods30 rats were divided into five groups. The first group was the control group. The second and fourth groups received 100 mg/kg and 200 mg/kg ZnO NP, respectively. The third and fifth groups received the same doses of ZnO NP as the second and fourth groups, respectively. However, the third and fifth groups received an additional dose of 1.3 gr/kg of LA amino acid. ZnO NP and LA are given intraperitoneal for 21 days. Blood samples from each rat and a part of the ovarium were collected to test for gene expression and histological analysis. ResultsCompared to levels of housekeeping gene β-actine, levels of apoptosis effectors such as Bax, Bcl, Caspase 3, and Caspase 9 were significantly increased in all groups. In groups that received doses of LA (three and five), atretic follicle size was smaller compared to groups that did not receive LA (two and four). In addition, in the third group, the secondary and primordial follicle's generated oocytes were smaller compared with groups two, four, and five. Compared with the control group, all groups experienced morphological degeneration of follicles and tissue. ConclusionZnO NP has inevitable, morphological, and physiological effects on the ovary and can detrimentally impact the tissue. LA can aid in the regeneration of the tissue and block damage induced by stress and toxicity.

KLHL24-Mediated Hair Follicle Stem Cells Structural Disruption Causes Alopecia

KLHL24 is an E3 ubiquitin ligase. Variants in the start codon of KLHL24 result in truncated KLHL24 protein lacking the initial 28 amino acids (KLHL24-ΔN28). KLHL24-ΔN28 is more stable than wild-type KLHL24 and causes excessive degradation of keratin 14, leading to epidermolysis bullosa. Patients with KLHL24-related epidermolysis bullosa usually develop alopecia, which is uncommon in patients with epidermolysis bullosa. The mechanisms by which KLHL24 variants cause alopecia is currently unclear. In this study, we show that KLHL24 regulates hair maintenance by mediating the stability of keratin 15. Using a Klhl24c.3G>T knock-in mouse model, we identify that KLHL24-ΔN28 disrupts the structure of hair follicle stem cells (HFSCs). Destructed HFSCs cannot anchor hairs and cause premature hair loss. Long-term destruction of HFSCs causes their exhaustion and hair follicle degeneration. Mechanically, KLHL24 mediates the ubiquitination and proteasomal degradation of keratin 15, an intermediate filament composing the HFSC cytoskeleton network. Keratin 15 is dramatically decreased in the skin of Klhl24c.3G>T mice and in patients with KLHL24-related epidermolysis bullosa. These findings show that KLHL24 plays a role in hair maintenance by regulating the cytoskeleton structure of HFSCs and highlight the importance of the ubiquitin‒proteasome system in the stability of HFSCs.