Hasan Alghetaa

Endometriosis (END) is a gynecological disease marked by the presence of endometrial-like tissue outside the uterus, inducing estrogen-driven inflammation that manifests through chronic pelvic pain, dysmenorrhea, and infertility, which impacts life quality. The pathophysiology of END involves genetic factors, hormonal imbalances, and immune disorders, generating pro-angiogenic and inflammatory environment. Resveratrol (RES), a naturally occurring polyphenol, recently became known as a potential therapeutic product owing to its diverse biological functions. This review examines the pathophysiological origins of END and clarifies the processes by which RES has therapeutic benefits. Resveratrol offers a novel, non-hormonal treatment strategy for endometriosis management by exhibiting anti-proliferative, anti-invasive, anti-adhesive, pro-apoptotic, antioxidant, anti-inflammatory, anti-angiogenesis, and hormone-modulating properties.

According to the most recent WHO report in 2022, about 16% of people were classified as obese. Obesity is an inflammatory-mediated condition manifested by accelerated lipogenesis and accumulation of excessive amounts of fat around the viscera and, in some cases, surrounds the male gonads. Thus, obesity is considered one of the major causes of male infertility. Many environmental toxicants known as obesogens are connected to obesity progression via disturbing hormonal profile, interrupting the cellular metabolism and subsequently leading to the development of fat tissue. Such toxicants like bisphenol A, a plastic derivative, as well as dioxins, which are byproduct of incomplete combustion or industrial processes. Interestingly, these types of toxicants, in addition to others like polycyclic aromatic hydrocarbons and polychlorinated biphenyls, are defined as ligands of aryl hydrocarbon receptor (AhR). AhR has critical roles in immunity, metabolism, reproduction, and cancer biology, and it is expressed in immune cells like T/B lymphocytes, macrophages, and dendritic cells. The effect of AhR on immunity is dependent on the ligand, which in turn could activate macrophage-induced obesity. Many of the ligands of AhR can be exogenous or endogenous (kynurenine and indole derivatives) and affect reproductive functions, such as spermatogenesis and oocyte maturation. There are also natural antagonists to AhR, including resveratrol, showing potential to play a role in fertility governance. .Currently, to connect the roles of AhR in obesity-induced male infertility. This review aims to elucidate the physiological/toxicological roles of AhR in obesity initiation and male infertility.

Background: Male infertility is a global concern and it tends to increase due to miscellaneous factors, such as environmental toxins and genetic and lifestyle choices. The aryl hydrocarbon receptor (AHR) has recently attracted attention due to its involvement in male infertility mechanisms and impact on sperm production and function. AHR, a versatile receptor expressed in various tissues, including the testes, regulates the genes involved in spermatogenesis. AHR activation is associated with cell cycle regulation and chromatin condensation during spermatogenesis. Objectives: This study aimed to investigate the influence of AHR activation on blood-testis barrier (BTB) integrity, focusing on the role of tight junction protein-1 (TJP1) and exploring the effects of AHR modulation on spermatogenesis outcomes in adult male rats. Methods: Forty adult male rats were divided into four groups according to their treatment regimens. Briefly, the control group was kept without any treatment, the resveratrol (RES) group received an intraperitoneal (IP) injection of 100 mg/kg every 72 h and the AHR antagonist (AHR‾) group received an IP injection of CH223191 at a dose of 10 mg/kg every 72 h. Finally, the dimethyl sulfoxide (DMSO) group received DMSO which was used as a solvent for preparing RES and CH223191. The study lasted for 60 d to cover the entire spermatogenesis cycle. At the study’s endpoint, sperm chromatin maturity and condensation were evaluated in addition to Tjp1 gene expression in testicular tissue, supported by BTB integrity assessment. Results: The abnormal sperm chromatin maturity (ASCM) and condensation were significantly (P<0.05) higher in AHR‾ compared to all other groups. Tjp1 gene expression was significantly upregulated in the RES group compared to the control and AHR‾ group, which tightened the BTB and maintained the testicular homeostasis for normal spermatogenesis. Conclusion: RES treatment positively influenced sperm chromatin maturity, Tjp1 expression and BTB integrity, suggesting its potential as a protective agent against male reproductive health. Conversely, AHR antagonism leads to compromised sperm chromatin integrity and BTB function, highlighting the critical role of AHR in spermatogenesis and BTB maintenance. These results underscore the importance of AHR modulation in male fertility and provide insights into potential therapeutic interventions.

Osteoporosis, a metabolic condition impacts bone health by affecting calcium metabolism. Aging and decreased estrogen levels lead to imbalanced endocrine function, increasing bone resorption and decreasing bone creation. Increased release of parathyroid hormone due to high phosphate intake results in hyperphosphatemia and the removal of calcium from the bone loading. The goal of this work was to develop a new method for quickly inducing osteoporosis in contrast to existing conventional techniques. Wistar female rats were exposed to ovariectomy and subsequently 10% phosphoric acid orally for 30 days to induce osteoporosis. Thirty adult Wistar female rats were equally divided into three groups: Naïve rats served as the control group (C), Bilateral ovariectomized rats (OVX group), and Sham group were exposed to the same surgical operation steps of OVX group without removing the ovaries. One week of recovery post-surgical operation, the OVX and Sham groups were given 10% phosphoric acid in drinking water for 30 days, following the removal of all surgical sutures and an inspection for any flaws. The outcomes demonstrated that the OVX and Sham groups had significantly lower bone density than the control group, despite that they had significantly higher levels of alkaline phosphates, osteocalcin, and parathyroid hormone. Interestingly, the OVX group's serum calcium levels were significantly lower than those of the control group. In conclusion, ovariectomy and 10% phosphoric acid administration enforced osteoporosis status via hyperphosphatemia, hyperparathyroidism, and disruption in the bone metabolism in female rats in relatively short-term induction, this practice is highly useful in investigations of bone metabolism and health.

Background and Aim: The aryl hydrocarbon receptor (AhR) plays a pivotal role in spermatogenesis through its regulatory functions in redox balance and gene expression. This study aimed to investigate the effects of resveratrol (RES), a polyphenolic AhR modulator, and CH223191, a selective AhR antagonist, on male reproductive function in rats by assessing sperm quality, oxidative stress, testicular histopathology, and AhR gene expression. Materials and Methods: Forty adult male rats were randomly divided into four groups: (i) Control, (ii) dimethyl sulfoxide (vehicle), (iii) RES (100 mg/kg i.p., twice weekly), and (iv) AhR⁻ (CH223191, 10 mg/kg i.p., twice weekly), treated for 60 days. Post-treatment, sperm motility, survival, viability, and DNA fragmentation were evaluated. Total antioxidant capacity (TAC), malondialdehyde (MDA) levels, testicular histopathology, and AhR gene expression quantitative polymerase chain reaction (qPCR) were analyzed. Results: RES significantly enhanced sperm motility, survival, and viability, reduced DNA fragmentation, and increased TAC while decreasing MDA levels. Histologically, RES preserved normal testicular architecture. In contrast, AhR inhibition through CH223191 led to marked reductions in sperm quality, elevated oxidative stress, increased DNA fragmentation, and severe testicular degeneration. qPCR analysis revealed upregulation of AhR expression in the RES group (fold change: +23.1%) and significant downregulation in the AhR⁻ group (fold change: −72.6%), indicating differential modulation of AhR signaling pathways. Conclusion: RES positively modulates AhR activity, safeguarding testicular structure and enhancing sperm quality through antioxidant and anti-apoptotic mechanisms. Conversely, AhR antagonism disrupts spermatogenesis, underscoring the receptor’s essential role in male fertility. These findings suggest the therapeutic potential of AhR-targeting agents like RES in ameliorating male reproductive dysfunctions associated with oxidative stress and xenobiotic exposure. Keywords: antioxidant capacity, aryl hydrocarbon receptor, resveratrol, CH223191, oxidative stress, sperm DNA fragmentation, spermatogenesis.

Male reproductive health is intricately regulated by molecular and physiological processes, with the aryl hydrocarbon receptor (AhR) playing a crucial role. AhR is activated by various ligands and influences the onset and progression of diseases. The aim of this study was to evaluate the role of AhR on spermatogenesis in adult male rats were affected by resveratrol (RES) and CH223191, an AhR antagonist. The study include forty rats were randomly divided into four equal groups: Control group, DMSO group, RES group and AhR‾ group, the rats received respective treatments intraperitoneally twice weekly for 60 days, and various parameters related to male reproductive health were evaluated. The AhR that activation by the RES treatment were enhanced the sperm morphology, sperm acrosomal integrity and luteinizing hormone. Moreover, the Dnah1 gene expression, is has play major role in sperm morphology, was upregulated and testosterone levels were elevated by RES. On the other hand, sperm morphology, sperm acrosomal integrity, testosterone hormone levels, and Dnah1 expression were all reduced in AhR‍ rats. The testicular tissue integrity was maintained by RES, according to a histopathological analysis. These findings highlight the role of AhR in male reproductive health and suggest RES as a potential therapeutic agent.

Mercuric chloride (HgCl2) pollution and poisoning has been a worldwide health ‎concern for decades, especially after the industrial revolutions. The aim of this study ‎was to investigate the role of resveratrol in reversing the deleterious effects of ‎HgCl2 exposure to resume the normal functions of hepatocyte. To achieve the study, ‎mature Sprague Dawley rats were assigned to five groups. Negative control group ‎‎(C) kept without any treatment; vehicle-treated group (D) received dimethyl ‎sulfoxide (DMSO); resveratrol-treated group (R), received 100 mg/kg of resveratrol; ‎HgCl2-intoxicated group (HD), received i.p. injection of HgCl2 at a dose of 1 mg/kg ‎for 30 consecutive days along to oral gavage of DMSO; and finally HgCl2-‎intoxicated group treated with resveratrol (HR) as same treatment strategy of R-‎group. At the endpoint of the experiment, blood samples were collected for ‎biochemical liver function tests along with serum concentrations of ‎malondialdehyde (MDA), glutathione (GSH), body weight, as well as ‎histopathological investigation was done too. Study results revealed a significant ‎‎(P<0.05) elevation in serum AST, ALP, GGT, and MDA in HD group in comparison ‎with HR group. However, resveratrol treatment has led to a significant (P<0.05) ‎increase in serum levels of GSH in HR group in comparison with the HD group. ‎Histopathological sections showed vacuolar degeneration in HD hepatocytes while ‎resveratrol treatment protected the hepatocytes against the chemical injury. ‎Altogether, It is concluded that resveratrol administration has the ability to increase ‎the resistance of liver against the HgCl2-induced hepatotoxicity via increase the ‎antioxidant yields such as GSH resulted in reduction of hepatocellular texture ‎damage.

| This study is designed to highlight some of the physiological disorders taken place in the renal function, immunological response as well as the ability of the redox system represented by total antioxidant capacity and malondialdehyde levels to combat the toxic exposure of mercuric chloride (HgCl2) with or without collaboration of resveratrol (RES) supplement. Forty-five adult Sprague Dawley, 8-10 weeks old female rats weighing 170-220 g were randomly grouped as following; control group (C) kept without any medication. Dimethyl sulfoxide (DMSO) used as vehicle to prepare RES treatment was given to D-group. RES administered to R-group. Challenge group of rats (HD) was administered HgCl2. The last group of rats (HR) was given HgCl2 with RES in the same doses mentioned earlier. All treatments lasted for four weeks. At the termination of the experiment, blood samples were collected to evaluate the renal function as well as to evaluate the redox system activity. Furthermore, peritoneal exudate was collected to determine the population of infiltrating cells by using trypan blue dye. Analyzed data revealed that there was renal dysfunction represented by significant (P<0.05) increase in blood urea of HD and HR groups in comparison with control group. Total antioxidants were significantly (P<0.05) higher in the blood of HR group than all others. Moreover, peritoneal exudate showed significant (P<0.05) exacerbation of immunocyte counts in HgCl2-administered groups in comparison with others. However, resveratrol administration to HR group drove the inflammatory cell counts to be significantly (P<0.05) lower than of HD group. Altogether, we can conclude that the resveratrol has the required biological effects to support the body responses against deleterious consequences of mercuric chloride poisoning.

Physiological status and litter size can indeed have a significant impact on ewes' ‎hematological parameters, which are essential indicators of their health. Therefore, this study ‎examined the hematological profiles of ewes during pregnancy with single and twins in the ‎Awassi ewes. The present study involved 232 ewes in good health and at sexual maturity. ‎Among them, 123 ewes had single pregnancies, while 109 ewes had twin pregnancies. The age ‎range of the ewes included in the study was between 3.5 and 4.5 years. Hematological tests ‎were conducted on the sheep's blood samples promptly following collection. The findings ‎demonstrated variations in hematological parameters among pregnant ewes, with differences ‎based on litter size. Ewes carrying twin pregnancies exhibited significantly higher levels of ‎red blood corpuscular, hemoglobin, packed cell volume, and mean corpuscular hemoglobin ‎concentration during pregnancy. In comparison to single-pregnant ewes, Awassi ewes with ‎twin pregnancies displayed elevated counts of white blood cells, lymphocytes, granulocytes, ‎and granulocyte percentage compared to ewes with single pregnancies. Awassi ewes with twin ‎pregnancies also exhibited a strong positive correlation with the leukocytes and erythrocytes ‎constituents. In conclusion, these findings indicate that litter size significantly influences ‎hematological parameters, highlighting the importance of considering the physiological status ‎and litter size as indicators of ewes' health. The findings have practical implications in sheep ‎breeding and reproduction, as they can be utilized to enhance the diagnosis, prognosis, and ‎treatment of related conditions‎.