StAR Gene Research Articles

AREG expression in cumulus cells as a prognostic marker of oocyte quality

Background. Assisted reproductive technologies (ART) represent the most promising and successful methods of infertility treatment. A personalized approach may enhance its efficacy. One such approach is the development of reliable methods for assessing the quality and selection of embryos for transfer. The quality of the embryo is largely contingent upon the quality of the gametes involved in fertilization; thus, the development of non-invasive methods to assess oocyte quality represents a crucial step in the advancement of personalized ART. It is proposed that molecular and biological characterization of cumulus cells can be utilized to assess oocyte quality and predict the success of implantation of transferred embryos. The aim of the study was to evaluate the expression levels of potential oocyte quality marker genes (AREG, STAR, PTGS2, HAS2 and SCD5) in cumulus cells from healthy donors and patients with primary and secondary infertility. Materials and Methods. Nine donors and 19 patients were enrolled in the study. RNA was isolated from cumulus cells obtained during oocyte preparation for fertilization, and cDNA was synthesized. The cDNA was used as a matrix for real-time PCR with primers for the above-mentioned genes of interest. Results. Significant difference in AREG gene expression was observed between patients with successful (i.e. ended with birth) outcome and with IVF failure. No difference was found for the STAR, HAS2, PTGS2 and SCD5 genes. Conclusion. The method of assessing the expression level of marker genes in cumulus cells by real-time PCR shows considerable promise for the assessment of oocyte quality. The AREG gene is a potential candidate for use as a marker of oocyte quality.

Human ovarian extracellular vesicles proteome from polycystic ovary syndrome patients associate with follicular development alterations.

The development of the ovarian follicle requires the presence of several factors that come from the blood and follicular cells. Among these factors, extracellular vesicles (EVs) represent an original communication pathway inside the ovarian follicle. Recently, EVs have been shown to play potential roles in follicular development and reproduction-related disorders, including the polycystic ovary syndrome (PCOS). The proteomic analysis of sEVs isolated from FF in comparison to sEVs purified from plasma has shown a specific pattern of proteins secreted by ovarian steroidogenic cells such as granulosa cells. Thus, a human granulosa cell line exposed to sEVs from FF of normal patients increased their progesterone, estradiol, and testosterone secretion. However, if the sEVs were derived from FF of PCOS patients, the activity of stimulating progesterone production was lost. Stimulation of steroidogenesis by sEVs was associated with an increase in the expression of the StAR gene. In addition, sEVs from FF increased cell proliferation and migration of granulosa cells, and this phenomenon was amplified if sEVs were derived from PCOS patients. Interestingly, STAT3 is a protein overexpressed in sEVs from PCOS patients interacting with most of the cluster of proteins involved in the phenotype observed (cell proliferation, migration, and steroid production) in granulosa cells. In conclusion, this study has demonstrated that sEVs derived from FF could regulate directly the granulosa cell activity. The protein content in sEVs from FF is different in the case of PCOS syndrome and could perturb the granulosa cell functions, including inflammation, steroidogenesis, and cytoskeleton architecture.

Nano Spirulina platensis countered cisplatin-induced repro-toxicity by reversing the expression of altered steroid hormones and downregulation of the StAR gene.

Cisplatin is a commonly utilized chemotherapy medication for treating different sarcomas and carcinomas. Its ability interferes with cancer cells' DNA repair pathways and postpones unfavorable outcomes in cancer patients. The current investigation's goal was to ascertain if nano Spirulina platensis (NSP) might shield rat testicles from cisplatin damage by assessing the expression of the StAR and SOD genes, sex hormones, 17ß-hydroxysteroid dehydrogenase(17ß-HSD), sperm profile picture, oxidative condition of testes, testicular histology, and DNA damage. Four equal and random groups of 28 adult male Wistar rats were created; the control group was given saline for 8weeks. An extraction of NSP at a concentration of 2500mg/kg body weight was administered orally for 8weeks to the NSP group. For the first 4weeks, the cisplatin group was intraperitoneally injected with 2mg/kg/body weight of cisplatin, and for the next 4weeks, they were given a dosage of 4mg/kg/body weight. The cisplatin + NSP group was given both NSP and cisplatin. The results of the experiment showed that intake of NSP and cisplatin improved sperm profile; re-established the balance of oxidizing agents and antioxidant state; enhanced testicular histology; promoted the histometric parameters of seminiferous tubules including epithelial height, their diameter, and Johnsen's score, decreasing DNA breakage in testicular tissue; increased testosterone level; decreased 17ß-HSD concentration; and upregulated both the StAR and SOD gene expression in testicles compared to rats exposed to cisplatin alone. These results demonstrate that NSP is a promising agent for improving cisplatin-induced testicular injury and infertility.

Effects of Chronic Stress and Comfort Food in Testicular Morphology in Adult Wistar Rats.

To investigate the effect of chronic stress on testicular morphology in adult Wistar rats, as well as the impact of comfort food consumption on these parameters. 32 Wistar rats (10 weeks old) were divided into four groups: control (C), stressed (S), control + comfort food (C+CF), and stressed + comfort food (S+CF). Chronic stress was induced by the restraint method during 8 weeks in groups S and S+CF, while groups C and C+CF were maintained under normal conditions. Groups C and S received a standard rat chow diet, while groups C+CF and S+CF received both the standard chow and comfort food (Froot Loops®). After 8 weeks of experiment, all animals were euthanized and the testes were collected for histomorphometric, immunohistochemical and gene expression analysis. Comfort food was preferred over standard chow in groups C+CF and S+CF, but this preference was more preeminent in stressed animals (S+CF). The consumption of comfort food resulted in testicular weight reduction. The seminipherous epithelium was reduced in group S in comparison to controls. While comfort food also reduced the epithelium in C+CF in comparison to controls, for group S+CF the comfort food ameliorated the stress-induced damage. The cell proliferation rate and the relative expression of StAR and BLC2 genes were similar between the groups. Both chronic stress and comfort food consumption resulted in morphological alterations of the testes but the consumption of comfort foods during chronic stress partially prevented the stress-induced detrimental effects on testes.

Bisphenol H exposure disrupts Leydig cell function in adult rats via oxidative stress-mediated m6A modifications: Implications for reproductive toxicity

Bisphenol H (BPH) has emerged as a potential alternative to bisphenol A (BPA), which has been curtailed for use due to concerns over its reproductive and endocrine toxicity. This study investigates whether BPH exerts antiandrogenic effects by impairing Leydig cell function, a critical component in testosterone production. We administered orally BPH to adult male rats at doses of 0, 1, 10, and 100 mg/kg/day for 7 days. Notably, BPH treatment resulted in a dose-dependent reduction in testicular testosterone levels, with significant decreases observed at ≥ 1 mg/kg/day. Additionally, BPH affected the expression of key genes involved in steroidogenesis and cholesterol metabolism, including Nr5a1, Nr3c4, Lhcgr, Scarb1, and Star, at higher doses (10 and/or 100 mg/kg/day). The study also revealed alterations in antioxidant gene expression (Sod2 and Cat) and modulation of m6A-related genes (Ythdf1–3 and Foxo3) and their proteins. Through MeRIP-qPCR analysis, we identified increased m6A modifications in Scarb1 and Star genes following BPH exposure. In vitro experiments with primary Leydig cells confirmed that BPH enhanced oxidative stress and diminished testosterone production, which were partially mitigated by antioxidant vitamin E supplementation and Ythdf3 knockdown. Meanwhile, simultaneous administration of BPH and vitamin E to primary Leydig cells partially counteracted BPH-induced alterations in the Ythdf3 expression. Our findings underscore a novel mechanism by which BPH disrupts Leydig cell function through the oxidative stress-m6A modification-autophagy pathway, raising concerns about its potential reproductive toxicity.

"Effect of Sunset Yellow on Testis: Molecular Evaluation, and Protective Role of Coenzyme Q10 in Male Sprague-Dawley Rats".

In recent years, Sunset Yellow (SY) has been widely used as a food additive, sparking debates about its potential toxicity. This research aims to investigate SY's effects at both the molecular and histopathological levels, along with the protective benefits of Coenzyme Q10 (CoQ10) supplementation in male rat testes. Forty-two male Sprague-Dawley rats were randomly divided into six groups (n = 7) and given daily oral gavages for six weeks. The groups included: a low dose of Sunset Yellow (2.5 mg/kg/day), a high dose of Sunset Yellow (70 mg/kg/day), CoQ10 (10 mg/kg/day), CoQ10 with the low dose of Sunset Yellow, CoQ10 with the high dose of Sunset Yellow, and deionized water as a control. After anesthesia, the rats' testes were removed for molecular and histological analysis. The findings showed a dose-dependent rise in the expression of oxidative stress genes (Sod, Gpx, and Cata) and a notable decrease in the expression of the steroidogenic acute regulatory (Star) gene (P value < 0.05) with increasing SY doses. Histological results supported these outcomes. Additionally, there was no significant distinction between rats treated with CoQ10 along with low doses of Sunset Yellow (CoQ10+LD) and control rats given low doses of Sunset Yellow (SY-LD). Conclusions: This study illustrates that SY, as an artificial food dye, has harmful effects on the male reproductive system, while the utilization of CoQ10 can alleviate the negative impacts of SY exposure.

Alterations in the Hypothalamic-Pituitary-Adrenal Axis as a Response to Experimental Autoimmune Encephalomyelitis in Dark Agouti Rats of Both Sexes.

Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system, usually diagnosed during the reproductive period. Both MS and its commonly used animal model, experimental autoimmune encephalomyelitis (EAE), exhibit sex-specific features regarding disease progression and disturbances in the neuroendocrine and endocrine systems. This study investigates the hypothalamic-pituitary-adrenal (HPA) axis response of male and female Dark Agouti rats during EAE. At the onset of EAE, Crh expression in the hypothalamus of both sexes is decreased, while males show reduced plasma adrenocorticotropic hormone levels. Adrenal gland activity is increased during EAE in both males and females, as evidenced by enlarged adrenal glands and increased StAR gene and protein expression. However, only male rats show increased serum and adrenal corticosterone levels, and an increased volume of the adrenal cortex. Adrenal 3β-HSD protein and progesterone levels are elevated in males only. Serum progesterone levels of male rats are also increased, although testicular progesterone levels are decreased during the disease, implying that the adrenal gland is the source of elevated serum progesterone levels in males. Our results demonstrate a sex difference in the response of the HPA axis at the adrenal level, with male rats showing a more pronounced induction during EAE.

The Effect of Prolactin on Gene Expression and the Secretion of Reproductive Hormones in Ewes during the Estrus Cycle.

Prolactin (PRL) plays an important role in animal follicle development and ovulation. However, its regulatory effects on the different stages of the estrus cycle in ewes are unclear. In this study, bromocriptine (BCR, PRL inhibitor) was used to study the effect of PRL on the secretion of reproductive hormones and gene expressions in order to explore its regulatory effects on the sexual cycle of ewes. Eighty healthy ewes with the same parity and similar weights were randomly assigned to the control group (C, n = 40) and the treatment group (T, n = 40, fed bromocriptine). After estrus synchronization, thirty-one ewes with overt signs of estrus were selected from each group. Six blood samples were randomly obtained by jugular venipuncture to measure the concentration of PRL, estrogen (E2), progesterone (P4), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and gonadotropin-releasing hormone (GnRH) in the proestrus, estrus, metestrus, and diestrus. At the same time, we collected the ovaries of the six ewes in vivo after anesthesia in order to detect follicle and corpus luteum (CL) counts and measure the expression of hormone-receptor and apoptosis-related genes. The results show that PRL inhibition had no significant effects on the length of the estrus cycle (p > 0.05). In proestrus, the number of large and small follicles, the levels of E2, FSH, and GnRH, and the expressions of ER, FSHR, and the apoptotic gene Caspase-3 were increased (p < 0.05); and the number of middle follicles and the expression of anti-apoptotic gene Bcl-2 were decreased (p < 0.05) in the T group. In estrus, the number of large follicles, the levels of E2 and GnRH, and the expressions of the StAR, CYP19A1, and Bcl-2 genes were increased (p < 0.05), and the number of middle follicles was decreased (p < 0.05) in the T group. In metestrus, the number of small follicles and the expression of LHR (p < 0.05) and the pro-apoptotic gene Bax were increased (p < 0.05); the number of middle follicles was decreased (p < 0.05) in the T group. In diestrus, the number of large follicles, middle follicles, and CL, the level of P4, and the expressions of PR, 3β-HSD, StAR, Caspase-3, and Bax were increased (p < 0.05); the number of small follicles and the expression of Bcl-2 were decreased (p < 0.05) in the T group. In summary, PRL inhibition can affect the secretion of reproductive hormones, the follicle count, and the gene expression during the estrus cycle. These results provide a basis for understanding the mechanisms underlying the regulation of the ewe estrus cycle by PRL.

Prevention of Male Late-Onset Hypogonadism by Natural Polyphenolic Antioxidants.

Androgen production primarily occurs in Leydig cells located in the interstitial compartment of the testis. In aging males, testosterone is crucial for maintaining muscle mass and strength, bone density, sexual function, metabolic health, energy levels, cognitive function, as well as overall well-being. As men age, testosterone production by Leydig cells of the testes begins to decline at a rate of approximately 1% per year starting from their 30s. This review highlights recent findings concerning the use of natural polyphenolics compounds, such as flavonoids, resveratrol, and phenolic acids, to enhance testosterone production, thereby preventing age-related degenerative conditions associated with testosterone insufficiency. Interestingly, most of the natural polyphenolic antioxidants having beneficial effects on testosterone production tend to enhance the expression of the steroidogenic acute regulatory protein (Star) gene in Leydig cells. The STAR protein facilitates the entry of the steroid precursor cholesterol inside mitochondria, a rate-limiting step for androgen biosynthesis. Natural polyphenolic compounds can also improve the activities of steroidogenic enzymes, hypothalamus-pituitary gland axis signaling, and testosterone bioavailability. Thus, many polyphenolic compounds such as luteolin, quercetin, resveratrol, ferulic acid phenethyl ester or gigantol may be promising in delaying the initiation of late-onset hypogonadism accompanying aging in males.

Severe adrenal insufficiency in six neonates with normal newborn screening for CAH.

Newborn screening (NBS) reduces the risk of mortality in congenital adrenal hyperplasia (CAH), mainly due to the salt-wasting form of 21-hydroxylase deficiency. There is limited knowledge regarding the results of NBS in non-CAH primary adrenal insufficiency (non-CAH PAI). Clinical and NBS for CAH data of neonates who were diagnosed with non-CAH PAI between January and December 2022 were examined. Patients (n = 6, 4 females) were presented with severe hyperpigmentation (n = 6), hypoglycemia (n = 4), hyponatremia (n = 3), hyperkalemia (n = 1), respiratory distress syndrome (n = 1) between 3rd hour to 2 months of life. All had normal NBS results. The median first-tier 17-hydroxyprogesterone (17OHP) concentration in NBS for CAH was 0.14 ng/mL (range; 0.05-0.85). Molecular studies revealed biallelic mutations in the MC2R (n = 4; 3 homozygous, 1 compound heterozygous), MRAP (n = 1) and STAR (n = 1) genes. Glucocorticoid with or without mineralocorticoid replacement was initiated once the diagnosis ofnon-CAH PAI was established. Neonates with non-CAH PAI have always normal NBS due to persistently low 17OHP, even when these newborn infants are severely symptomatic for adrenal insufficiency. Clinicians should be alert for signs of adrenal insufficiency in neonates, even if the patient has a 'normal' screening for CAH, so as not to delay diagnosis and treatment. This fact should be kept in mind particularly in countries where these conditions are more common than elsewhere.

The mollifying effect of Sambucus nigra extract on StAR gene expression, oxidative stress, and apoptosis induced by fenpropathrin in male rats

Fenpropathrin (FNP) is a man-made insecticide of to the pyrethroid class, commonly employed in agricultural and horticultural practices. However, it has a prolonged persistence in the environment. Sambucus nigra, also referred to as SN, is a botanical species recognized for its notable antioxidant characteristics. The objective of this study was to examine if SN extract could mitigate the reproductive toxicity induced by FNP in rats. A total of thirty rats were categorized into six distinct groups: a control group with no treatment, two groups getting SN extract at varying doses, a group receiving FNP, and two groups receiving both FNP and SN extract. The exposure to FNP led to a decline in the number and movement of sperm, lowered levels of testosterone, and reduced the activity of the StAR gene in the FNP group compared to the control group (p < 0.05). In addition, FNP resulted in a significant increase in malondialdehyde levels with a significant drop in GSH content compared to the control group (p < 0.05). Also, a significant increase in the expression of caspase 3. Nevertheless, the administration of SN extract alleviated these effects and reinstated spermatogenesis, thereby bringing the parameters closer to those observed in the control group. The data indicate that FNP can induce testicular harm and infertility, but SN extract can mitigate these detrimental consequences.

Star1 gene mutation reveals the essentiality of 11-ketotestosterone and glucocorticoids for male fertility in Nile Tilapia (Oreochromis niloticus)

Steroidogenic acute regulatory protein (Star) plays an essential role in the biosynthesis of corticosteroids and sex steroids by mediating the transport of cholesterol from the outer to the inner membrane of mitochondria. Two duplicated Star genes, namely star1 and star2, have been identified in non-mammalian vertebrates. To investigate the roles of star genes in fish steriodogenesis, we generated two mutation lines of star1−/− and star1−/−/star2−/− in Nile tilapia (Oreochromis niloticus). Previous studies revealed that deficiency of star2 gene caused delayed spermatogenesis, sperm apoptosis and sterility in male tilapia. Our present data revealed that mutation of star genes impaired male fertility. Disordered seminiferous lobules and spermatic duct obstruction were found in the testis of both types of mutants. Moreover, significant decline in semen volume, sperm abnormality and impaired fertility were also detected in star1−/− and star1−/−/star2−/− males. In star1−/− male fish, lipid accumulation, up-regulation of steroidogenic enzymes, and significant decline of androgens were found. Additionally, hyperplasic interrenal cells, elevated steroidogenic gene expression level and decline of serum glucocorticoids were detected in star1 mutants. Intriguingly, either 11-KT or cortisol supplementation successfully rescued the impaired fertility of the star1−/− mutants. Taken together, these results further indicate that Star1 might play critical roles in the production of both 11-KT and glucocorticoids, which are indispensable for the maintenance of male fertility in fish.

Assessment of the Effect of Leonurine Hydrochloride in a Mouse Model of PCOS by Gene Expression Profiling.

Polycystic ovary syndrome (PCOS) is an endocrine disease commonly associated with metabolic disorders in females. Leonurine hydrochloride (Leo) plays an important role in regulating immunity, tumours, uterine smooth muscle, and ovarian function. However, the effect of Leo on PCOS has not been reported. Here, we used dehydroepiandrosterone to establish a mouse model of PCOS, and some mice were then treated with Leo by gavage. We found that Leo could improve the irregular oestros cycle of PCOS mice, reverse the significantly greater serum testosterone (T) and luteinising hormone (LH) levels, significantly reduce the follicle-stimulating hormone (FSH) level, and significantly increase the LH/FSH ratio of PCOS mice. Leo could also change the phenomenon of ovaries in PCOS mice presented with cystic follicular multiplication and a lacking corpus luteum. Transcriptome analysis identified 177 differentially expressed genes related to follicular development between the model and Leo groups. Notably, the cAMP signalling pathway, neuroactive ligand-receptor interactions, the calcium signalling pathway, the ovarian steroidogenesis pathway, and the Lhcgr, Star, Cyp11a, Hsd17b7, Camk2b, Calml4, and Phkg1 genes may be most related to improvements in hormone levels and the numbers of ovarian cystic follicles and corpora lutea in PCOS mice treated by Leo, which provides a reference for further study of the mechanism of Leo.

Barley sprouts and D-Aspartic acid supplementation improves fertility, hatchability, and semen quality in aging male broiler breeders by up-regulating StAR and P450SCC gene expressions

At 50 wk of age, broiler breeder roosters exhibit a significant decline of fertility. Therefore, the aim of this study was to assess the impact of incorporating barley sprout (BS) powder, D-aspartic acid (DA), or their combination into the diet on fertility, hatchability, semen quality, and the relative expression of StAR and P450SCC genes in aging broiler roosters. Aging (50 wk) male broiler breeders (n=32) were randomly assigned to one of four dietary treatments (2 × 2 factorial) with 2 levels of BS (0 or 2% basal diet) and DA (0 or 200 mg/kg/BW) for 12 wk. Roosters were individually housed under a 14-h light and 10-h dark cycle, with 150 g/d feed allocation and free access to fresh water, then euthanized. Throughout the study, the body weight of the broiler breeders was measured, along with various parameters related to semen quality, on a weekly basis. Additionally, artificial insemination was performed during the last 2 wk to evaluate reproductive endpoints. The results revealed that both BS and DA decreased (P < 0.01) body weight. Interestingly, the inclusion of BS, either alone or in combination with DA, resulted in a significant increase in total and forward sperm motility. Furthermore, it was demonstrated that the seminal concentration of malondialdehyde, a marker of oxidative stress, was significantly decreased by more than 20% in all groups compared to the control. The combination of both BS and DA led to the highest levels of circulating testosterone, as well as the functionality and membrane integrity of sperms. Additionally, it resulted in increased sperm concentrations, production, and penetration, ultimately leading to improved fertility rate and hatchability percentage. Moreover, a positive association between total motility and fertility was observed (P < 0.01). Furthermore, the combined supplementation of BS and DA up-regulated the relative mRNA expression of P450scc and StAR (P < 0.01). To summarize, dietary inclusion of BS, DA, or their combination have a potential to improve various aspects of reproductive performance in aging roosters.

The effect of adipose tissue StAR gene expression on ICSI among Polycystic Ovarian Syndrome cases and matched controls: a case-control study

The effect of adipose tissue StAR gene expression on ICSI among Polycystic Ovarian Syndrome cases and matched controls: a case-control study

Retama raetam Extract for Testicular Health in Type 2 Diabetic Rats: Insight View on the Steroidogenesis, Antioxidants, and Molecular Docking Scores of Bioactive Compounds against Bax

The exponential growth of obesity rates is a pressing issue, as it is now firmly established as a primary driver behind the development of metabolic disorders. Natural products are crucial in drug discovery, prompting an increasing need for further research on bioactive compounds to understand molecular and pharmacological mechanisms and expand available clinical treatments for various diseases. We set out to investigate the therapeutic potential of Retama raetam (RR) extract, a natural compound, in alleviating testicular degeneration and improving sperm quality and quantity in high-fat diet (HFD)-induced type 2 diabetes mellitus (T2DM) and streptozotocin (STZ)-induced type 2 diabetes mellitus. An eight-week high-fat diet (HFD) was administered to type 2 diabetic rats, and then a modest dose of 35 mg/kg of STZ was injected intraperitoneally. The experiment planned to assess the influence of RR extract on the steroidogenesis pathway. For twelve weeks, the rats were given medications orally. The testicular degeneration caused by HFD/STZ is shown by decreasing the accessory sexual glands while reducing the quality of sperm characters and testosterone levels with significantly increased pad fat and leptin levels. Furthermore, administration of RR extract effectively counteracted HFD/STZ-induced oxidation through enhancing the antioxidant status of the testicular tissue through significantly increased SOD and GSH accompanied by decreasing MDA. HFD/STZ rats showed decreased expression of CYP17, STAR, 3βHSD, and BCL2 genes, along with increased BAX gene expression. However, treatment with RR in HFD/STZ rats led to decreased BAX expression and increased expression of CYP17, STAR, 3βHSD, and BCL2 genes, indicating a restoration of gene expression values similar to the control group. The binding site of Bax showed a strong affinity for several bioactive compounds found in R. raetam. The findings from this study suggest that Retama raetam (RR) has the potential as a therapeutic adjunct for managing complications related to type 2 diabetes mellitus (T2DM). These findings afford credence to the idea that RR can be useful in treating infertility associated with type 2 diabetes.

Fertility protection: a novel approach using pretreatment with mesenchymal stem cell exosomes to prevent chemotherapy–induced ovarian damage in a mouse model

BackgroundPrimary ovarian insufficiency (POI) refers to the loss of ovarian functionbefore the age of 40 years and results in amenorrhea and infertility. POI has diverse causes, but a common cause is exposure to gonadotoxic chemotherapy for cancer treatment. Due to the risk of developing POI, patients who want to preserve their fertility may consider various procedures for fertility preservation. However, current fertility preservation options are highly invasive, carry substantial risks, and have uncertain success rates. Recent studies from our group and others reported that mesenchymal stem cells (MSCs) and MSC-derived exosomes can restore ovarian functions in preclinical models of POI by restoring damaged cells and inhibiting apoptosis. Although the restorative effect of MSC-derived exosomes has been well reported in previous studies, the potential of MSC-derived exosomes for preventing ovarian damage has not been fully elucidated. ObjectiveWe hypothesized that the antiapoptotic potential of MSC-derived exosomes may protect ovarian tissue from chemotherapy-induced damage. Study designIn this study, we delivered MSC-derived exosomes directly into mouse ovaries before chemotherapy. Sixty mice were divided into three groups (20 per group), which were labeled the control, CTx (chemotherapy), and FP (fertility protection) groups. Only the FP group mice received exosomes, while the control and CTx group mice received saline. After exosome injection, the CTx and FP groups of mice were subjected to chemotherapy treatment to induce ovarian damage. After chemotherapy, we evaluated the protective effects of exosome treatment on ovarian function, such as estrus cyclicity, serum hormone levels, and the fertility rate, by comparing these outcomes between the CTx and FP groups. These outcomes were also compared with those of the control group for comparison with outcomes under healthy conditions. ResultsAfter intraovarian injection of exosomes before chemotherapy, the mice were able to maintain their estrus cycle (4–5-day cyclicity), serum AMH level (66.06±26.40 ng/ml, not significantly different from that of the healthy controls), folliculogenesis (32.2±11.3 in the CTx group/46.4±14.1 in the FP group, p<0.05), steroidogenesis marker StAR gene expression (0.44±0.11-fold in the CTx group and 0.88±0.31-fold in the FP group, p<0.05), and fertility (2 of 8 in the CTx group and 5 of 8 in the FP group), preventing chemotherapy-induced damage. We found that exosome treatment before chemotherapy can preserve ovarian function and protect fertility through the overexpression of ABC transporters, such as ABCB1b (10.17±17.75-fold in the CTx group and 44.14±33.25-fold in the FP group; p<0.05), and ABCC10 (3.25±0.59-fold in the CTx group and 5.36±1.86-fold in the FP group; p<0.05). ConclusionIn this study, we present a novel fertility protection method using MSC-derived exosomes. We conclude that MSC-derived exosomes are a promising simple treatment option for fertility protection in reproductive-age patients receiving gonadotoxic chemotherapy.

Using Selenium-enriched Mutated Probiotics as Enhancer for Fertility Parameters in Mice.

Increasing fertility rates have become one of the factors that concern all people in the world. Therefore, the study aims to use two mutated strains of probiotics enriched with selenium (PSe40/60/1 and BSe50/20/1) to improve fertility. Thirty Swiss albino male mice were divided into three groups; control, LP + S was given Lactobacillus plantarum PSe40/60/1 plus selenium, and BL + S was given Bifidobacterium longum BSe50/20/1 plus selenium. Free testosterone, LH, and FSH were measured in serum by biochemical analysis. Testicular tissues were examined by histopathological analysis. The count and motility of sperm, and sperm abnormalities were determined by microscopic examination. The method of qRT-PCR was used to detect gene expression of Tspyl1, Hsd3b6, and Star genes. The biochemical results showed that serum content of free testosterone (FT) hormone had significantly increase in the BL + S and LP + S groups compared with control. Levels of LH and FSH hormones were the highest in the BL + S group. The treated groups showed all developmental stages of spermatogenesis, including spermatogenesis, spermatocytes, and seminiferous tubule spermatids, as well as intact Sertoli cells and Leydig cells without changes. When compared to the control group, sperm count and motility increased in the BL + S group, while sperm abnormalities decreased. The expression of Tspyl1 gene in testicular tissues decreased in the LP + S and BL + S groups, while the expression of Star and Hsd3b6 genes was higher in the BL + S group and lower in the LP + S group compared with the control group. Therefore, Bifidobacterium longum BSe50/20/1 enriched with selenium could be useful in enhancing male fertility.

Ameliorative effects of rutin and rutin-loaded chitosan nanoparticles on testicular oxidative stress and histological damage induced by cyclophosphamide in male rats

Cyclophosphamide (CP) is broadly used to kill various tumor cells; however, its repeated uses have been reported to cause reproductive dysfunction and infertility. Natural flavonoid, rutin (RUT), possesses strong antioxidant and antiapoptotic activity that is attributed to ameliorate the reproductive dysfunction induced by CP. Many previous studies proved that the formulation of flavonoids in nanoemulsion has a promising perspective in mitigating the side effects of chemotherapy. Therefore, the main objective of this study was to investigate the ameliorative effects of RUT and RUT-loaded chitosan nanoparticles (RUT-CH NPs) against CP-induced reproductive dysfunction in male rats. For this aim, thirty-six male albino rats were randomly allocated into six groups as follows: control, RUT, RUT-CH NPs, CP, CP + RUT, and CP + RUT-CH NPs. In the CP groups, a single intraperitoneal injection of CP (150 mg/kg bwt) was administered on the first day of the experiment. RUT and RUT-CH NPs were orally administered either alone or with CP injection at a dose of 10 mg/kg bwt per day for 60 days. The results revealed that CP administration caused significant testicular oxidative stress damage through increasing the nitric oxide and malondialdehyde levels as well as decreasing the total antioxidant capacity and reduced glutathione contents. It also impaired spermatogenesis and steroidogenesis via altering the transcription levels of CYP11A1, HSD-3b, StAR, Bax, bcl-2, and Nrf-2 genes. Otherwise, the oral intake of either RUT or RUT-CH NPs with CP injection effectively attenuated these alterations and significantly improved the microscopic appearance of testicular tissue. In conclusion, this study highlights the potential of RUT either free or NPs in mitigating CP-induced testicular dysfunction via its antioxidant and anti-apoptotic properties.

Ameliorative effect of Odontonema cuspidatum extract against testicular damage induced by sodium nitrite in rats.

Sodium nitrite (NaNO2) is a chemical substance used to enhance taste, add color, and keep food products fit for consumption for a longer time. NaNO2 gives rise to a negative adverse effect on male reproductive function. Odontonema cuspidatum (OC) is a natural plant that possesses antioxidant capacity. Our research evaluates the potential beneficial effect of OC extract on the harmful effects caused by NaNO2 on the testicular tissue and sperm characteristics of male rats. Four groups with a total of forty rats: the control, the NaNO2-received group, the OC-administered group, and the fourth group received both NaNO2 and OC. All groups were administered daily for two months. Sperm characteristics, testicular antioxidant status, qRT-PCR, and histopathological changes were evaluated. Coadministration of NaNO2 and OC, in comparison with NaNO2 alone, contributed to a notable enhancement in acrosomal integrity, decreasing sperm abnormalities and restoring serum testosterone levels. Moreover, such coadministration reduced the oxidative stress marker, malondialdehyde (MDA), and increased superoxide dismutase (SOD) in testicular tissue, lowering TNF-α gene expression, and increasing the expression of P450scc and StAR genes. In addition, the NaNO2 and OC combination decreased the testicular histopathological changes and the Caspase-3 and Proliferating cell nuclear antigen (PCNA) immunoexpression in seminiferous tubules compared with the NaNO2 group. The extract of OC exhibited the ability to decrease oxidative stress and ameliorate the detrimental effects caused by NaNO2.