Effects of Natural Polyphenols on Skin and Hair Health: A Review.

The skin is the largest organ of the body and plays multiple essential roles, ranging from regulating temperature, preventing infections, to ultimately affecting human health. A hair follicle is a complex cutaneous appendage. Skin diseases and hair loss have a significant effect on the quality of life and psychosocial adjustment of individuals. However, the available traditional drugs for treating skin and hair diseases may have some insufficiencies; therefore, a growing number of researchers are interested in natural materials that could achieve satisfactory results and minimize adverse effects. Natural polyphenols, named for the multiple phenolic hydroxyl groups in their structures, are promising candidates and continue to be of scientific interest due to their multifunctional biological properties and safety. Polyphenols have a wide range of pharmacological effects. In addition to the most common effect, antioxidation, polyphenols have anti-inflammatory, bacteriostatic, antitumor, and other biological effects associated with reduced risk of a number of chronic diseases. Various polyphenols have also shown efficacy against different types of skin and hair diseases, both in vitro and in vivo, via different mechanisms. Thus, this paper reviews the research progress in natural polyphenols for the protection of skin and hair health, especially focusing on their potential therapeutic mechanisms against skin and hair disorders. A deep understanding of natural polyphenols provides a new perspective for the safe treatment of skin diseases and hair loss.

Prenatal exposure to endocrine-disrupting chemicals and thyroid function in neonates: A systematic review and meta-analysis.

Thyroid hormone homeostasis is essential for normal brain development in fetuses and infants. Exposure to endocrine-disrupting chemicals (EDCs) during pregnancy is associated with compromised maternal thyroid homeostasis, and thus may lead to adverse neurodevelopmental outcomes in newborns. However, evidence regarding the association of prenatal EDC exposure and thyroid hormones in newborns is controversial. Therefore, a meta-analysis to elucidate the relationship between maternal exposure to EDCs and neonatal THs was performed. A systematic search of PubMed, EMBASE, and the Cochrane Library (CENTRAL) for relevant published studies that provided quantitative data on the association between prenatal EDC exposure and neonatal thyroid hormones was conducted in August 2021. To calculate the overall estimates, we pooled the adjusted ß regression coefficients with 95% confidence intervals (CIs) from each study by the inverse variance method. The pooling results indicated that prenatal EDC exposure had no significant influence on neonatal TSH, TT3, FT3, TT4 or FT4 level in the global assessment. However, in the specific exposure and outcome assessment, we found that prenatal exposure to organochlorine (ß coefficient, -0.022; 95% CI, -0.04 to -0.003) and PFAS (ß coefficient, -0.017; 95% CI, -0.033 to 0) was negatively associated with neonatal TT4 level. In conclusion, prenatal exposure to organochlorine and PFAS may be associated with lower neonatal TT4 level.

Retardation of Preputial Wound Healing in Rats with Hypospadias Induced by Flutamide.

Objective: The aim of this study was to identify a theoretical support for the prevention of urethral fistula following hypospadias repair, by comparing the preputial wound healing process in Sprague-Dawley (SD) rats with and without hypospadias induced by flutamide. Methods: Fifteen pregnant SD rats were randomly divided into three groups. These rats in one group received the androgen receptor antagonist flutamide (25 mg/kg/day) from gestation days 11-17, to establish a rat model of hypospadias for further study of the molecular mechanisms of the hypospadias etiology. The pregnant rats in the control groups were not administered flutamide. The pups from the control and experiment groups underwent an incision on the dorsal prepuce on postnatal day 25 and were sacrificed on postoperative days 3, 7, and 14 to collect penis samples. The penis morphology was examined in all groups. Subsequently, transforming growth factor ß1 (TGF-ß1), α-smooth muscle actin (α-SMactin), and signal transducers and activators of the transcription 3 (STAT3) expression levels in the different groups were measured at the indicated time points postoperatively using qRT-PCR and Western blot. Results: There was less regeneration of the subcutaneous tissue in hypospadias rats than in the sham-operated group (P < 0.05) on postoperative day 3. No differences were found in the regeneration of the subcutaneous tissue between these groups on postoperative days 7 or 14. Additionally, there were no differences in the epithelial cell regeneration between the control and the hypospadias groups at any postoperative timepoint. Moreover, the expression levels of TGF-ß1, α-SMactin, and STAT3 were all significantly lower in hypospadias group than that in the sham-operated group (P < 0.05). Conclusion: The results from the present work suggest that preputial wound healing is retarded in rats with hypospadias induced by flutamide and that this retardation might result from multi-gene regulation.

Vitamin E and vitamin C attenuate Di-(2-ethylhexyl) phthalate-induced blood-testis barrier disruption by p38 MAPK in immature SD rats.

As an environmental endocrine disruptor, Di-(2-ethylhexyl) phthalate (DEHP) affects blood-testis barrier (BTB)-associated proteins expression, which compromises BTB integrity and causes infertility. Notably, DEHP-induced testicular toxicity is related to oxidative stress, but the specific mechanism remains unclear. Therefore, we sought to investigate this mechanism and determine whether vitamin C and vitamin E administration would attenuate the BTB impairment induced by DEHP in vivo and by Mono-(2-Ethylhexyl) Phthalate (MEHP) in vitro, respectively. HE staining and EM found that DEHP exposure led to spermatogenesis dysfunction and BTB disruption, respectively. The Western blot and immunofluorescence results showed that DEHP exposure caused BTB impairment through oxidative stress-mediated p38 mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, Vitamin E and vitamin C could alleviate the oxidative stress, block DEHP-induced spermatogenesis dysfunction and BTB disruption by inhibiting p38 MAPK signaling pathway. In summary, vitamin E and vitamin C are good candidates for the treatment of DEHP-induced male infertility.

Di-(2-ethylhexyl) phthalate (DEHP)-induced testicular toxicity through Nrf2-mediated Notch1 signaling pathway in Sprague-Dawley rats.

Di-(2-ethylhexyl) phthalate (DEHP) is an environmental endocrine disruptor widely used in China that is harmful to the male reproductive system. Many studies have shown that DEHP causes testicular toxicity through oxidative stress, but the specific mechanism is unknown. Because the Notch pathway is a key mechanism for regulating cell growth and proliferation, we investigated whether Notch is involved in DEHP-induced testicular toxicity and whether vitamins E and C could rescue testicular impairment in Sprague-Dawley (SD) rats. Compared with the control group, we found that DEHP exposure induced testicular toxicity through oxidative stress injury, and it decreased the testosterone level (P < .01) and upregulated nuclear factor-erythroid 2 related factor (Nrf2) expression (P < .01). Therefore, because oxidative stress might be the initiating factor of DEHP-induced testicular toxicity, treatment with the antioxidant vitamins E and C activated the Notch1 signaling pathway in the testis and in Leydig cells. Treatment with vitamins E and C normalized the oxidative stress state after DEHP exposure and restored testicular development to be similar to the control group. In summary, antioxidant vitamins E and C may be used to treat DEHP-induced testicular toxicity.

Urban fine particulate matter (PM2.5) exposure destroys blood-testis barrier (BTB) integrity through excessive ROS-mediated autophagy.

CONTEXT: Blood-testis barrier (BTB), constituted by tight junctions (TJs), adherens junctions and gap junctions, is important for spermatogenesis. PM2.5 is known to impair testicular functions and reproduction. However, its effects on BTB and the underlying mechanisms remain obscure. OBJECTIVE: To investigate the roles of autophagy in BTB toxicity induced by PM2.5. MATERIALS AND METHODS: Sprague-Dawley rats were developmentally exposed to normal saline (NS) or PM2.5 with the doses of 9 mg/kg b.w. and 24 mg/kg b.w. via intratracheal instillation for seven weeks. Success rate of mating, sperm quality, testicular morphology, expressions of BTB junction proteins and autophagy-related proteins were detected. In addition, expressions of oxidative stress markers were also analyzed. RESULTS: Our results demonstrated that developmental PM2.5 exposure induced noticeable decreased fertility, significantly reduced sperm count, increased sperm abnormality rate and severe testicular damage in histomorphology. The expressions of TJ (such as ZO-1 and occludin), gap junction (such as connexin43) were down-regulated significantly after PM2.5 treatment. Intriguingly, PM2.5 simultaneously increased the number of autophagosomes and the levels of autophagy marker LC3-II and p62, suggesting that the accumulated autophagosomes resulted from impaired autophagy degradation. Moreover, the expressions of HO-1 levels remarkably increased and expression levels of Gpx and SOD were significantly decreased after PM2.5 exposure. Vitamins E and C could alleviate the PM2.5-induced oxidative stress, reverse the autophagy defect and restore the BTB impairment. CONCLUSIONS: Taken together, the results suggest that PM2.5 exposure destroys BTB integrity through excessive ROS-mediated autophagy. Our finding could contribute to a better understanding of PM2.5-induced male reproductive toxicity.

Epithelial-mesenchymal transformation and apoptosis in rat urethra development.

BackgroundTo examine the mechanism of urethral seam formation during embryonal development of rat urethra.MethodsTime-mated Sprague-Dawley rats were killed and the genital tubercles of male pups harvested on embryonic day (ED) 15, 16, 18, and 19. External morphology was observed under scanning electron microscope. Serial transverse sections were prepared to examine dynamic changes in the urethral seam morphology with hematoxylin-eosin staining, immunohistochemistry, transmission electron microscopy, and double immunofluorescence.ResultsBilateral outgrowth of urethral swelling followed by urethral plate fusion in the midline to form urethral seam was observed from ED 16 onwards. Coexpression of epithelial and mesenchymal markers was observed in several cells at the urethral seam; a few cells with coexpression of epithelial and apoptotic markers were also observed. Mesenchymal transformation of epithelial cells and apoptotic epithelial cells was observed under transmission electron microscope.ConclusionUrethral formation occurs by tubulogenesis, which initiates proximally and progresses distally. This is the first study to demonstrate epithelial-mesenchymal transformation and epithelial cell apoptosis in the urethral seam cells of fetal rats. These findings provide new insights into the mechanisms involved in embryonal development of the urethra.

[Effect of Di-(2-ethylhcxyl) phthalate exposure on blood-testis barrier integrity in rats].

OBJECTIVE: To investigate mechanism of di-(2-ethylhcxyl)phthalate (DEHP) exposure in causing blood-testis barrier (BTB) impairment in rats. METHODS: Two-months-old male SD rats were randomly divided into corn oil control group and DEHP (750 mg/kg) exposure group for daily intragastic treatment for 30 consecutive days. After the treatments the rats were examined for histomorphological changes of the testicle using HE staining and the expressions of the junction proteins N-cadherin ß-catenin, occludin and connexin43 of the BTB using Western blot. In the in vitro study, the vitality and ROS generation level in Sertoli cells exposed to different concentrations of DEHP were examined with MTT and ROS assay kits, respectively, and Nrf2 and p-p38 expressions were detected with Western blot. RESULTS: Compared with the control group, the rats with DEHP exposure showed structural damage of the seminiferous tubule and polarity loss of the spermatids. DEHP exposure caused significantly decreased expressions of occludin and connexin43 but increased expressions of N-cadherin and ß-catenin in the testicle tissues of the rats (P<0.05). The vitality of Sertoli cells was obviously decreased and ROS level increased significantly after exposure of the cells to increasing concentrations of DEHP, which also resulted in significantly up-regulated Nrf2 and p-p38 expressions (P<0.05). CONCLUSIONS: DEHP exposure causes increased oxidative stress in the Sertoli cells of the testis, activates p38 MAPK signaling pathway, and results eventually in impaired spermatogenesis in rats.

Urban fine particulate matter exposure causes male reproductive injury through destroying blood-testis barrier (BTB) integrity.

Blood-testis barrier (BTB) provides a suitable microenvironment for germ cells that is required for spermatogenesis. Exposure to particulate matter (PM) is recognized to occasion male reproductive impairment, but the mechanism of which remains unclear. Male Sprague-Dawley (SD) rats were used to establish animal models with PM2.5 exposure concentration of 0, 10, and 20mg/kg.b.w. once a day for four weeks. Success rate of mating, sperm quality, epididymal morphology, expressions of spermatogenesis markers, superoxide dismutases (SOD) activity and expression in testicular tissues, and expressions of BTB junction proteins were detected. In addition, in vitro experiments were also performed. After PM2.5 treatment, reactive oxygen species (ROS) production and apoptosis of Sertoli cells were analyzed. Our results indicated that after PM2.5 exposure male rats presented inferior uberty and sperm quality, with decreased expressions of spermatogenesis markers, escalated SOD activity and expression levels, and reduced expressions of tight junction, adherens junction, and gap junction proteins in testicular tissues. Meantime, PM2.5-treated Sertoli cells displayed increased SOD production and apoptosis. PM2.5 exposure engenders male reproductive function injury through breaking BTB integrity.

New discovery of cryptorchidism: Decreased retinoic acid in testicle.

This study focuses on investigation of cryptorchidism induced by flutamide (Flu) and its histopathological damage, and detects retinoic acid concentration in testicle tissue, in order to find a new method for clinical treatment to infertility caused by cryptorchidism. Twenty SD (Sprague Dawley) pregnant rats were randomly divided into Flu cryptorchidism group (n = 10) and normal control group (n = 10). HE stained for observing morphological difference. Transmission electron microscope (TEM) was used for observing the tight junction structure between Sertoli cells. Epididymal caudal sperms were counted and observed in morphology. The expression of stimulated by retinoic acid gene 8 (Stra8) was detected using immunohistochemistry, western blot, and Q-PCR. High performance liquid chromatography (HPLC) analysis was made on retinoic acid content. Sperm count and morphology observation confirmed cryptorchidism group was lower than normal group in sperm quantity and quality. The observation by TEM showed a loose structure of tight junctions between Sertoli cells. Immunohistochemistry, western blot, and Q-PCR showed that cryptorchidism group was significantly lower than normal group in the expression of Stra8. HPLC showed that retinoic acid content was significantly lower in cryptorchid testis than in normal testis. In the cryptorchidism model, retinoic acid content in testicular tissue has a significant reduction; testicles have significant pathological changes; damage exists in the structure of tight junctions between Sertoli cells; Stra8 expression has a significant reduction, perhaps mainly contributing to spermatogenesis disorder.

[Long-term exposure to PM2.5 from automobile exhaust results in reproductive dysfunction in male rats].

OBJECTIVE: To explore the effects of long-term exposure to particulate matter 2.5 (PM2.5) from automobile exhaust on the reproductive function of Sprague Dawley (SD) rats. METHODS: Forty-five male SD rats, weighing 80 - 94 g and aged 28 days, were randomly assigned to receive intra-tracheal administration of 0.9% normal saline (control group, n = 15), PM2. 5 at 2 µg per 100 g body weight per day (low-dose PM2.5 group, n = 15), and PM2.5 at 16 µg per 100 g body weight per day (high-dose PM2.5 group, n = 15), qd, for 60 successive days. After the last 24-hour exposure, 10 rats were taken from each group for copulation with normal female ones, while the others were sacrificed, their testes removed for sperm count and deformity, pathological examination, and determination of the Connexin43 expression. RESULTS: The conception rate was significantly decreased in the low- and high-dose PM2.5 groups as compared with that of the control (70% and 50% vs 100%), and so were the sperm count and quality. The rats in the PM2.5-exposed groups showed significantly disordered histological structure of the seminiferous tubules, reduced sperm count in the testicular lumen, some exfoliated secondary spermatocytes, downregulated Connexin43 expression in the testis, and damaged blood-testis barrier. CONCLUSION: Long-term exposure to PM2.5 from automobile exhaust damages the reproductive function of male SD rats.

The Mechanism of Environmental Endocrine Disruptors (DEHP) Induces Epigenetic Transgenerational Inheritance of Cryptorchidism.

Discussion on the role of DEHP in the critical period of gonadal development in pregnant rats (F0), studied the evolution of F1-F4 generation of inter-generational inheritance of cryptorchidism and the alteration of DNA methylation levels in testis. Pregnant SD rats were randomly divided into two groups: normal control group and DEHP experimental group. From pregnancy 7 d to 19 d, experimental group was sustained to gavage DEHP 750 mg/kg bw/day, observed the incidence of cryptorchidism in offspring and examined the pregnancy rate of female rats through mating experiments. Continuous recording the rat's weight and AGD value, after maturation (PND80) recording testis and epididymis' size and weight, detected the sperm number and quality. Subsequently, we examined the evolution morphological changes of testicular tissue for 4 generation rats by HE staining and Western Blot. Completed the MeDIP-sequencing analysis of 6 samples (F1 generation, F4 generation and Control). DEHP successfully induced cryptorchidism occurrence in offspring during pregnancy. The incidence of cryptorchidism in F1 was 30%, in F2 was 12.5%, and there was no cryptorchidism coming up in F3 and F4. Mating experiment shows conception rate 50% in F1, F2 generation was 75%, the F3 and F4 generation were 100%. HE staining showed that the seminiferous epithelium of F1 generation was atrophy and with a few spermatogenic cell, F2 generation had improved, F3 and F4 generation were tend to be normal. The DNA methyltransferase expression was up-regulated with the increase of generations by Real Time-PCR, immunohistochemistry and Western Blot. MeDIP-seq Data Analysis Results show many differentially methylated DNA sequences between F1 and F4. DEHP damage male reproductive function in rats, affect expression of DNA methyltransferase enzyme, which in turn leads to genomic imprinting methylation pattern changes and passed on to the next generation, so that the offspring of male reproductive system critical role in the development of imprinted genes imbalances, and eventually lead to producing offspring cryptorchidism. This may be an important mechanism of reproductive system damage.

Fine particulate matter leads to reproductive impairment in male rats by overexpressing phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway.

Maintenance of male reproductive function depends on normal sperm generation during which process Sertoli cells play a vital role. Studies found that fine particulate matter (PM) causes decreased male sperm quality, mechanism of which unestablished. We aim to investigate the definite mechanism of PM impairment on male reproduction. Male Sprague-Dawley rats were daily exposed to normal saline (NS) or PM2.5 with the doses of 9 mg/kg.b.w and 24 mg/kg.b.w. via intratracheal instillation for seven weeks. Reproductive function was tested by mating test and semen analysis after last exposure. Testes were collected to assess changes in histomorphology, and biomarkers including connexin 43 (Cx43), superoxide dismutase (SOD), phosphatidylinositol 3-kinase (PI3K) and phosphorylated protein kinase B (p-Akt). Male rats exposed to PM2.5 showed noticeable decreased fertility, significantly reduced sperm count, increased sperm abnormality rate and severe testicular damage in histomorphology. After PM2.5 exposure, the levels of Cx43 was significantly downregulated, and SOD was upregulated and downregulated significantly with different dose, respectively. Protein expression of PI3K and p-Akt dramatically enhanced, and the later one being located in Sertoli cells, the upward or declining trend was in dose dependent. PM2.5 exposure leads to oxidative stress impairment via PI3K/Akt signaling pathway on male reproduction in rats.