Induced Pluripotent Stem Cell-Derived Parathyroid Organoids Resemble Parathyroid Morphology and Function.

The primary role of the parathyroid glands is to maintain calcium homeostasis through the secretion of parathyroid hormone (PTH). The limited proliferative capacity and differentiation of parathyroid cells hinder the generation of cell therapy options. In this study, parathyroid organoids are successfully generated from human-induced pluripotent stem cells (hiPSCs). At the end of the 20 days of differentiation, the parathyroid organoids exhibited distinct parathyroid morphology. Stereomicroscope, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) analysis demonstrated the 3D arrangement of the cell layers in which intracellular structures of parathyroid cells resemble human parathyroid cellular morphology. Comprehensive molecular analyses, including RNA sequencing (RNA-Seq) and liquid chromatography/mass spectrometry (LC-MS/MS), confirmed the expression of key parathyroid-related markers. Protein expression of CasR, CxCr4, Gcm2, and PTH are observed in parathyroid organoids. Parathyroid organoids secrete PTH, demonstrate active intercellular calcium signaling, and induce osteogenic differentiation via their secretome. The tissue integration potential of parathyroid organoids is determined by transplantation into parathyroidectomized rats. The organoid transplanted animals showed significant elevations in PTH-related markers (CasR, CxCr4, Foxn1, Gcm2, and PTH). PTH secretion is detected in organoid-transplanted animals. The findings represent a significant advancement in parathyroid organoid culture and may offer a cellular therapy for treating PTH-related diseases, including hypoparathyroidism.

Protective role of vitamin E against acrylamide-induced testicular toxicity from pregnancy to adulthood: insights into oxidative stress and aromatase regulation.

Acrylamide (ACR) is a toxic chemical frequently encountered in daily life, posing health risks. This study aimed to elucidate the molecular-level mechanism of ACR's toxic effects on testicles and investigate whether Vitamin E can mitigate these effects. A total of 40 adult pregnant rats were utilized, divided into four groups: Control, ACR, Vitamin E, and ACR + Vitamin E. ACR and Vitamin E were administered to the mother rats during pregnancy and lactation, and to the male offspring until the 8th week post-birth. Serum hormone levels, oxidant-antioxidant parameters, histopathological examination of testicular tissue, and mRNA and protein levels of the testicular and liver aromatase gene were analyzed. Spermiogram analysis was conducted on the collected sperm samples from the male offspring. The results revealed that ACR exposure adversely affected hormone levels, oxidant-antioxidant parameters, histological findings, as well as aromatase gene and protein expressions. However, Vitamin E administration effectively prevented the toxic effects of ACR. These findings demonstrate that ACR application significantly impairs the reproductive performance of male offspring rats by increasing liver aromatase activity.

Nerolidol attenuates dehydroepiandrosterone-induced polycystic ovary syndrome in rats by regulating oxidative stress and decreasing apoptosis.

AIMS: Although nerolidol (NRL) is a naturally occurring sesquiterpene alcohol with many pharmacological activities, its role in dehydroepiandrosterone DHEA-induced polycystic ovary syndrome PCOS is unknown. This study aims to explore the potential beneficial effects and underlying molecular mechanisms of nerolidol treatment on polycystic ovary syndrome. MAIN METHODS: Pre-pubertal female Sprague-Dawley rats were randomly assigned into four groups (n = 8/group); group I: control; group II: PCOS; group III: P + NRL; group IV: NRL. Biochemical parameters related to oxidative stress, inflammation, apoptosis, and hormones were estimated in the blood and ovarian tissues. Histopathological, ultrastructural, and immunohistochemical analyses were performed. Bax, P53, Cas-3, and Bcl-2 gene expression levels were detected with RT-PCR. The membrane array analysis detected chemokine, cytokine, and growth factor protein profiles. KEY FINDINGS: In light of the available data, it can deduce that nerolidol has a significant ameliorating effect on lipid peroxidation, oxidative stress, inflammation, histopathological damage, and apoptosis accompanying PCOS in female rats. SIGNIFICANCE: PCOS is not only a reproductive pathology but also a systemic condition and its etiopathogenesis is still not fully understood. Since changes in PCOS have important long-term effects on health, this study evaluated the efficacy of nerolidol, a phytotherapeutic for the control of biochemical, apoptotic, histopathological, and metabolic changes.

The effect of aromatase inhibitors against possible testis toxicity in pembrolizumab treated rats.

Pembrolizumab is a monoclonal antibody. Anastrozole is an infertility inhibitor of aromatase. Resveratrol is an antioxidant polyphenol in the reproductive system. This study was planned to demonstrate the protective effects of anastrozole and resveratrol against pembrolizumab-induced reproductive damage. Forty-two Sprague-Dawley rats were used in the study. Groups: The control, Pembrolizumab (PEMB), PEMB + Anastrazol (ANAST), PEMB + Resveratrol (RES), RES, and ANAST groups. At the end of the experiment, rats were euthanased under anaesthesia. Tissue samples were taken from rats for biochemical, histological, and ELISA evaluations. Tissues were subjected to routine tissue follow-up for histological analysis. Biochemically, thiobarbituric acid reactive substance (TBARS), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) levels were measured. Sperm motility, abnormal sperm rate, and epididymal sperm concentration were examined spermatologically. Serum testosterone and programmed cell death-1 (PD-1) levels were measured using the ELISA. TBARS levels were significantly increased and GSH, SOD, GPx, and CAT levels were mitigated in PEMB-treated rats. Histologically; Control, ANAST, and RES groups testis samples were observed with normal histological appearance. Histological damage was detected in seminiferous tubule structures in testicular tissue in the PEMB group. In treatment groups, this damage was decreased. In addition, PD-1 and testosterone levels were evaluated by the ELISA method. ANAST and RES have therapeutic effects against reproductive damage caused by PEMB.

Investigation of protective effect of ellagic acid in phthalates-induced reproductive damage.

Phthalates that people are exposed to every day are toxic carcinogenic chemicals with proven harmful effects on growth and reproduction. Ellagic acid (EA) is a polyphenol derivative known for its antioxidant properties. We hypothesized that the possible reproductive damage mechanism of phthalates is oxidative attack and ellagic acid could have a protective effect against radical forms in the body through its antioxidant properties. Thirty-two male rats were randomly divided into 4 groups, with 8 rats in each. Phthalate (DBP) was administered intraperitoneally and EA acid through gastric oral gavage (phthalate group 500 mg/kg/day DBP; EA group 2 mg/kg/day ellagic acid; the treatment group 500 mg/kg/day DBP and 2 mg/kg/day EA). The vehicle of DBP and EA, carboxymethyl cellulose was administered to control group. At the end of 4 weeks the testis tissue samples were taken under mild anesthesia. Tissue malondialdehyde, antioxidant parameters, sperm motility, sperm density and abnormal spermatozoon ratios were determined. Analysis was performed with One Way ANOVA test using SPSS 12.0 program. As a result; it has been shown that DBP causes oxidative damage by increasing the malondialdehyde level and decreasing antioxidant parameters, increased abnormal sperm rate and decreased sperm motility and concentration and histopathological damage so this damage is inhibited by the antioxidant activity of ellagic acid.

Favourable effect of ß-glucan treatment against cisplatin-induced reproductive system damage in male rats.

The aim of this study was to investigate the potential beneficial effects of ß-glucan treatment against oxidative, histological and spermatological damage caused by cisplatin on the male reproductive system. Twenty-eight Sprague Dawley male rats were used in the study. The rats were randomly divided into four equal-sized groups: a control group, cisplatin group (7 mg/kg in a single-dose cisplatin administered intraperitoneally), ß-glucan group (ß-glucan given at a dose of 50 mg kg-1  d-1 for 14 day) and a cisplatin plus ß-glucan group (cisplatin and ß-glucan administered together at the same dose). Cisplatin administration induced an increase in the level of thiobarbituric acid-reactive substances, a lipid peroxidation indicator. It induced a decrease in enzymatic (superoxide dismutase, catalase and glutathione peroxidase) activities and nonenzymatic (reduced glutathione) antioxidant levels. In addition, cisplatin caused both histological and spermatological damage, as shown by a decrease in sperm motility and epididymal sperm concentrations and an increase in abnormal sperm rates. The ß-glucan treatment improved cisplatin-induced oxidative, histological and spermatological damage. This study revealed that ß-glucan treatment provided prevention against male reproductive system damage caused by cisplatin. These preventative effects were likely due to its antioxidant properties.

Effects of pomegranate juice consumption on sperm quality, spermatogenic cell density, antioxidant activity and testosterone level in male rats.

BACKGROUND & AIM: Pomegranate fruit is inescapably linked with fertility, birth and eternal life because of its many seeds. The aim of this study was to investigate the effects of pomegranate juice (PJ) consumption on sperm quality, spermatogenic cell density, antioxidant activity and testosterone level of male healthy rats. METHODS: Twenty-eight healthy adult male Wistar rats were divided into four groups; each group containing seven rats. One milliliter distilled water, 0.25 mL PJ plus 0.75 mL distilled water, 0.50 mL PJ plus 0.50 mL distilled water and 1 mL PJ were given daily for seven weeks by gavage to rats in the first, second, third and fourth groups, respectively. Body and reproductive organ weights, spermatogenic cell density, sperm characteristics, levels of antioxidant vitamins, testosterone, and lipid peroxidation and, antioxidant enzyme activities were investigated. All analyses were done only once at the end of the seven week study period. Data were compared by analysis of variance (ANOVA) and the degree of significance was set at P<0.05. RESULTS: A significant decrease in malondialdehyde (MDA) level and marked increases in glutathione (GSH), glutathione peroxidase (GSH-Px) and catalase (CAT) activities, and vitamin C level were observed in rats treated with different doses of PJ. PJ consumption provided an increase in epididymal sperm concentration, sperm motility, spermatogenic cell density and diameter of seminiferous tubules and germinal cell layer thickness, and it decreased abnormal sperm rate when compared to the control group. CONCLUSION: The results suggest that PJ consumption improves sperm quality and antioxidant activity of rats.

Use of cauda epididymis extract as immunocontraceptive.

The objective of this study was to evaluate use of a cauda epididymis extract (CEE) as an immunocontraceptive in rats. Twenty-two rats in puberty or 19 rats that gave birth once (primipara) were immunized with intraperitoneal (IP) injection of CEE. Rats in puberty received one or two injections of CEE containing 1.5 x 10(9) sperm/mL, while primipara rats received injections of CEE containing 3 x 10(6) sperm/mL up to three times. Animals were tested for the presence and concentration of anti-CEE antibody by enzyme-linked immunosorbent assay (ELISA) and monitored for pregnancy following natural insemination. Results revealed that 38 (92.6%) of the 41 rats were positive for anti-CEE antibodies, regardless of animal type or immunization procedure. However, there was no relation between pregnancy rates and concentration of anti-CEE antibody in rats immunized with CEE. These results indicate that immune response against CEE may not play a major role in contraception in rats.