Hormonal Control Research Articles

Role of L-glutamine in the regulation of rat Sertoli cell proliferation by FSH.

FSH leads to glutamine dependence, which is required for mTORC1 activation and in consequence Sertoli cell proliferation. The spermatogenic capacity of adult individuals depends on, among other factors, the number of Sertoli cells (SCs) that result from the proliferative waves during development. FSH upregulates SC proliferation at least partly, through the activation of the PI3K/Akt/mTORC1 pathway, among other mechanisms. It is widely known that mTORC1 is a sensor of amino acids. Among amino acids, glutamine acquires relevance since it might contribute to cell cycle progression through the modulation of mTORC1 activity. It has not been studied yet whether glutamine intervenes in FSH-mediated regulation of SC proliferation and cell cycle progression, or if FSH has any effect on glutamine metabolism. Eight-day-old rat SCs were incubated in culture media without glutamine or with glutamine in the absence or presence of a glutamine transporter inhibitor or a glutaminase activity inhibitor under basal conditions or stimulated with FSH. The results obtained show that FSH does not promote SC proliferation and mTORC1 activation in the absence of glutamine. Also, FSH modulates glutamine metabolism increasing glutaminase isoform 2 and reducing glutamine synthetaseexpression. FSH did not promote SC proliferation and mTORC1 activation when glutaminase activity was inhibited. The results suggest that glutamine or its metabolites might cooperate with FSH in the upregulation of SC proliferation through mTORC1. In addition, as FSH modulates glutamine metabolism through the induction of glutaminase isoform 2, the hormonal control of glutamine metabolism might be part of the intricate signaling network triggered by FSH, which is crucial to establish the population of mature SCs that supports the reproductive function.

Astrocytes: a star emerges in the control of reproductive hormones.

Kisspeptin is an essential neuropeptide sitting at the apex of the hypothalamo-pituitary-gonadal (HPG) endocrine axis to regulate gonadotropin-releasing hormone (GnRH) neurons and downstream reproductive hormones. Kisspeptin neurons integrate feedback from sex steroids facilitating regulation of the menstrual cycle and mediate the effects of metabolic stressors on the reproductive axis. In this issue of the JCI, Torres and colleagues describe another pathway for kisspeptin signaling in astrocytes to influence GnRH neuronal output. Astrocytes had kisspeptin receptors that activated canonical intracellular signaling pathways to constrain the magnitude of kisspeptin-induced GnRH neuronal stimulation. Additionally, the appositions between kisspeptin and GnRH neurons were dynamic during the ovarian cycle, with astrocyte kisspeptin signaling proposed as a putative modulator of this neuroplasticity. Importantly, astrocyte kisspeptin signaling also mediated susceptibility to metabolic stressors and the development of obesity-induced hypogonadism, underscoring the physiological and pathological importance of this pathway and revealing the importance of nonneuronal signaling in reproductive health.

EFFECTS OF HORMONAL THERAPY IN TRANSGENDERS

People who change their gender after birth are known as transgender people. They underwent surgical transformation along with hormonal therapy. Hormonal imbalance is the most common phenomenon in the transgender community due to hormonal therapy and other related issues. Hormonal therapy is essential for gender transformation, but this therapy poses several risks to the individual who is taking this therapy. Transgender people who are under hormonal therapy are more at risk of cardiovascular disorders as certain hormones like estrogen and testosterone, besides their intended function, also induce side effects, due to which individuals taking these hormones become more prone to cardiovascular disorder, irregular blood pressure, brain function, and structure start changing. The cross-sex hormone therapy is also associated with brain tumors, changes in body mass index, and several skin conditions. Such hormones also affect bone density in different individuals due to changes in the deposition pattern of calcium into the bone under hormonal control. Hormonal therapy causes certain metabolic disorders as well, and certain hormones interact with other hormones in a different way when they are not naturally produced in the body. The voice of such people undergoing gender transformation also changes due to the testosterone level. This review summarizes some aspects of hormonal therapy, but whether or not a person undergoes such transition is their choice.

Adaptive endocrine PID control for active suspension based on reinforcement learning

Adaptive endocrine PID control for active suspension based on reinforcement learning

Effects and action mechanism of gonadotropins on ovarian follicular cells: A novel role of Sphingosine-1-Phosphate (S1P). A review

Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) control antral follicular growth by regulating several processes, such as the synthesis of hormones and signaling molecules, proliferation, survival, apoptosis, luteinization, and ovulation. To exert these effects, gonadotropins bind to their respective Gs protein-coupled receptors, activating the protein kinase A (PKA) pathway or recruiting Gq proteins to activate protein kinase C (PKC) signaling. Although the action mechanism of FSH and LH is clear, recently, it has been shown that both gonadotropins promote the synthesis of sphingosine-1-phosphate (S1P) in granulosa and theca cells through the activation of sphingosine kinase 1. Moreover, the inhibition of SPHKs reduces S1P synthesis, cell viability, and the proliferation of follicular cells in response to gonadotropins, and the addition of S1P to the culture medium increases the proliferation of granulosa and theca cells without apparent effects on sexual steroid synthesis. Therefore, we consider that S1P is a crucial signaling molecule that complements the canonical gonadotropin pathway to promote the proliferation and viability of granulosa and theca cells.

Bruton's tyrosine kinase (BTK) inhibitors alter blood glucose and insulin in obese mice but reduce inflammation independent of BTK.

Obesity is associated with metabolic inflammation, which can contribute to insulin resistance, higher blood glucose, and higher insulin indicative of prediabetes progression. The nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a metabolic danger sensor implicated in metabolic inflammation. Many features of metabolic disease can activate the NLRP3 inflammasome; however, it is not yet clear which upstream triggers to target, and there are no clinically approved NLRP3 inflammasome inhibitors for metabolic disease. Bruton's tyrosine kinase (BTK) mediates activation of the NLRP3 inflammasome. Ibrutinib is the most-studied pharmacological inhibitor of BTK, and it can improve blood glucose control in obese mice. However, inhibitors of tyrosine kinases are permissive, and it is unknown if BTK inhibitors require BTK to alter endocrine control of metabolism or metabolic inflammation. We tested whether ibrutinib and acalabrutinib, a new generation BTK inhibitor with higher selectivity, require BTK to inhibit the NLRP3 inflammasome, metabolic inflammation, and blood glucose in obese mice. Chronic ibrutinib administration lowered fasting blood glucose and improved glycemia, whereas acalabrutinib increased fasting insulin levels and increased markers of insulin resistance in high-fat diet-fed CBA/J mice with intact Btk. These metabolic effects of BTK inhibitors were absent in CBA/CaHN-Btkxid/J mice with mutant Btk. However, ibrutinib and acalabrutinib reduced NF-κB activity, proinflammatory gene expression, and NLRP3 inflammasome activation in macrophages with and without functional BTK. These data highlight that the BTK inhibitors can have divergent effects on metabolism and separate effects on metabolic inflammation that can occur independently of actions on BTK.NEW & NOTEWORTHY Bruton's tyrosine kinase (BTK) is involved in immune function. It was thought that BTK inhibitors improve characteristics of obesity-related metabolic disease by lowering metabolic inflammation. However, tyrosine kinase inhibitors are permissive, and it was not known if different BTK inhibitors alter host metabolism or immunity through actions on BTK. We found that two BTK inhibitors had divergent effects on blood glucose and insulin via BTK, but inhibition of metabolic inflammation occurred independently of BTK in obese mice.

Hormonal and Genetic Controls of Hirsutism: Link Between hyperprolactinemia, Polycystic ovary syndrome and Hirsutism

Hormonal and Genetic Controls of Hirsutism: Link Between hyperprolactinemia, Polycystic ovary syndrome and Hirsutism

Astounding the anxiolytic and eudemonic potential of certain fruits

Anxiety is a state of mind with some fear that affects physical health by disrupting neurotransmission and hormonal control. Both diet (inadequate and unhealthy dietary patterns) and environment (social and financial factors) trigger its progression; therefore, diet is considered to have a significant involvement in its prevention or adjunct therapy. A unique nutrient profile and bioactive ingredients are seen in fruits to provide health outcomes beyond nutritive properties. The relaxing potential of such fruits is attributed to the functional nature and therapeutic ingredients i.e., catecholamines, myricetin, quercetin, betalains, etc. that enhance the efficiency of hormones, neurotransmitters, and metabolic pathways. This review presented certain fruits having positive associations with mental health and anxiety amelioration. Various types of research evidenced the anxiolytic effect of certain fruits through clinical trials. Among them, berries, opuntia, and black pepper also have shown anxiety-relieving effects in clinical studies by restoring antioxidant enzymes, hormonal modulations, and managing neurotransmitters. Citrus species are loaded with flavonoids which are involved in the expression of GABA (Gamma-Amino Butyric Acid) to calm the nervous system. Some other fruits also potentiate memory and cognition when taken in ample amounts owing to their secondary metabolites. Thus, the incorporation of such fruits into a regular diet has been found to have a significant impact on mental well-being and brain health.

Surgical outcome of endoscopic endonasal approach as a modality of management for large and giant pituitary adenomas: a retrospective case series

BackgroundLarge and giant pituitary adenomas (defined as tumors of maximal diameter ≥ 3–3.9 cm and ≥ 4 cm, respectively) present considerable surgical challenges regarding the extent of resection and perioperative morbidity. Endoscopic endonasal resection is considered the most effective treatment for pituitary adenomas. It allows for better visualization, maneuverability, and access to distant and lateral tumor compartments, ultimately enhancing the extent of resection. This article evaluates our initial experience with endoscopic endonasal resection of large and giant pituitary adenomas. The clinical outcomes, perioperative complications, and extent of tumor resection would be specifically addressed.Patients and methodsThe primary goal of surgery was to decompress the optic pathways, and the secondary goals were to achieve maximal safe resection and hormonal control in hormone-secreting adenomas. The degree of tumor resection was classified as gross-total resection (100%), near-total resection (90–100%), subtotal resection (70–90%), and partial resection (< 70%).Results42 patients were included in this study. A good visual outcome achieved with 80% improvement in visual symptoms. Gross-total resection (GTR) was achieved in 19 patients (45.2%), near-total resection (NTR) was achieved in 12 patients (28.6%), subtotal resection (STR) in 6 patients (14.3%), and partial resection in the remaining 5 patients (11.9%). Subgroup analysis revealed that GTR, NTR rates were higher in large, compared to giant tumors. GTR, NTR rates of large adenomas were 59.3%, and 29.6%, compared to 20%, and 26.7% in giant adenomas respectively (p-value: 0.01428). Surgical complications were observed in 19 patients (45.2%) with CSF leakage being the most common complication (11 patients, 26.2%). Post-operative diabetes insipidus was observed in 5 patients (11.9%), major vascular injury in one case (2.4%), transient post-op 6th nerve palsy observed in 3 patients (7.1%), while two patients (4.8%) presented with post-operative paranasal sinuses infection.ConclusionsEndoscopic endonasal transsphenoidal resection of large and giant pituitary adenomas is a safe and efficient procedure. Large adenomas (3–3.9 cm) have excellent resection rates and lower complications than giant adenomas (≥ 4 cm), which may require extending our approach to achieve more tumor resection rates in the future. However, only adequate resection of these giant adenomas can be enough to achieve the main surgical goals of visual improvement, hormonal control, and decompression of surrounding structures.

The Effects of Interval and Traditional Resistance Exercise on Hormonal Control of Adipose-tissue Lipolysis in Healthy Young Men

Purpose: Lipolysis is regulated by lipolytic hormones, like insulin, cortisol, growth Hormone (GH), and catecholamines. Unregulated lipolysis results in the accumulation of free fatty acids (FFAs), leading to dysfunction of cells and death. Thus, the main aim of this study was to determine the effects of interval and traditional resistance exercise on hormonal control of adipose-tissue lipolysis in healthy young men. Methods: Twelve healthy males (Mean ± SD; age, 25.5 ± 3.1 years; Body mass index, 24.2 ± 2.0 kg/m2) performed tradition resistance exercise (TRE) at 80% of 1RM (3 sets of 6 repetitions) with 2 min passive recovery, and an interval resistance exercise (IRE) trial at 60% of 1RM (3 sets of 6 repetitions) followed by active recovery (1 set of 6 repetitions at 20% of 1RM). Three blood samples were taken before and immediately after exercise, and after one-hour recovery and were analyzed to measure epinephrine, norepinephrine, cortisol, and GH. Results: Statistical analyses of the data revealed that concentrations of cortisol and GH increased in response to resistance exercise and significantly decreased (p &lt; 0.05) during the recovery period. Although there were no significant differences between the two protocols for cortisol concentration, GH increases following IRE were profoundly higher than TRE protocol. Epinephrine and norepinephrine increased (p &lt; 0.05) in response to both resistance exercise trials, though, no between-group differences were found for these variables. Conclusion: The results of our study showed increases in GH, cortisol, epinephrine, and norepinephrine in two resistance exercise protocols which may lead to increases in fat oxidation.

The mlpt smORF gene is essential for digestive physiology and molting during nymphal stages in the kissing bug Rhodnius prolixus

Chagas disease affects around 8 million people globally, with Latin America bearing approximately 10,000 deaths each year. Combatting the disease relies heavily on vector control methods, necessitating the identification of new targets. Within insect genomes, genes harboring small open reading frames (smORFs - < 100 amino acids) present numerous potential candidates. In our investigation, we elucidate the pivotal role of the archetypal smORF-containing gene, mille-pattes/polished-rice/tarsalless (mlpt/pri/tal), in the post-embryonic development of the kissing bug Rhodnius prolixus. Injection of double-stranded RNA targeting mlpt (dsmlpt) during nymphal stages yields a spectrum of phenotypes hindering post-embryonic growth. Notably, fourth or fifth stage nymphs subjected to dsmlpt do not undergo molting. These dsmlpt nymphs display heightened mRNA levels of JHAMT-like and EPOX-like, enzymes putatively involved in the juvenile hormone (JH) pathway, alongside increased expression of the transcription factor Kr-h1, indicating changes in the hormonal control. Histological examination reveals structural alterations in the hindgut and external cuticle of dsmlpt nymphs compared to control (dsGFP) counterparts. Furthermore, significant changes in the vector's digestive physiology were observed, with elevated hemozoin and glucose levels in the posterior midgut of dsmlpt nymphs. Importantly, dsmlpt nymphs exhibit impaired metacyclogenesis of Trypanosoma cruzi, the causative agent of Chagas disease, underscoring the crucial role of proper gut organization in parasite differentiation. Thus, our findings constitute the first evidence of a smORF-containing gene's regulatory influence on vector physiology, parasitic cycle, and disease transmission.

Effects of preduodenal ileal surgical transposition on enteroendocrine intestinal cells in wistar rats: Histomorphological and serum changes.

In our study, we focused on the role of the distal ileum as a main endocrine actor in relation to the pancreas. We investigated the effects of intestinally released hormones on the pancreas in terms of type 2 diabetes mellitus (T2DM) improvement, as a main effect of bariatric surgeries. To specifically study the importance of the ileum, we used an experimental surgical model performed in healthy Wistar rats. After preduodenal transposition of the ileum, we analyzed the histology and enterohormonal cells of the intestine. We measured the plasma level of several hormones and effectors in this enteropancreatic axis. We used a surgical control (Sham) group and a surgical group, where ileum preduodenal transposition (PDIT) was performed. We measured basal glycemia and serum levels of several incretins, including GLP-1, PYY, and GIP, and we performed a glucose overdose test. After two test periods, the basal glycemia and glucose overdose results were not different between groups, however, the PDIT group had significantly increased expression of GLP-1, with increased cellular release in the ileum and duodenum compared with the Sham group. Both plasma GIP levels and GIP tissue expression were decreased in the PDIT group compared with the sham group. There were no differences in PPY hormone levels. The ileum crypts and villi of the PDIT group showed improvement in histological parameters. We concluded that model animals had an altered transposed ileum related to the enterohormonal adaptation of the ileum. Our results indicated that the ileum is important in the hormonal control of the enteropancreatic axis.

Surgical Outcome of the Endoscopic Endonasal Approach in Giant Pituitary Adenomas: A Systematic Review

Abstract Background Pituitary adenomas are the third most common intracranial tumors comprising about 10%–15% of all tumors. Giant pituitary adenomas (GPAs) are a subset of pituitary tumors. Most giant adenomas are slowly growing and histologically benign in nature despite the giant in size and difficulties to manage. Diverse surgical techniques including microscopic transsphenoidal, endoscopic transsphenoidal, transcranial transcavernous, and a combination of both suprasellar and infrasellar techniques have been developed to treat giant tumors with extension into surrounding structures. The development of the endonasal endoscopic approach for the resection of pituitary adenomas has been one of the most important advances for the treatment of pituitary tumors in the last decades since 1997. Aim of the Work analyze the collective outcomes from studies discussing endoscopic endonasal transsphenoidal approach in managing giant pituitary adenomas regarding extent of tumor resection, visual improvement and hormonal control. Methodology This systematic review included a discussion of all available studies meeting the eligible criteriaincluding: well conducted descriptive studies, cohort, articles, analytic studies and the literature of reviews. Results Surgical intent of gross or near total resection, primarily for the purpose of improving outcome, can be complicated by injuries that lead to a worse outcome and protracted clinical course. In this respect, patient-oriented outcomes (POEMs) are a point of emphasis in this review. Conclusion The endoscopic endonasal approach is an effective approach for giant pituitary adenomas with high rates of near or complete resection, visual improvement, and low rate of complications.

Contrary to phylogenetic predictions, crown coloration of the Eared Dove is not regulated by sex hormones

The mechanisms regulating plumage coloration appear to be phylogenetically conserved in avian species: the plesiomorphic character state is estrogen-dependent regulation, while testosterone, luteinizing hormone, and non-hormonal control are derived states. Limited data exist on the underlying regulatory processes of sexual dichromatism in the Eared Dove ( Zenaida auriculata (Des Murs, 1847)). Since the Columbiformes order is close to basal branches, we hypothesized that estrogen and testosterone play a central role in the regulation of crown plumage coloration in the Eared Dove. To test this, we subjected adult males to a forced molt accompanied by an exogenous increase of estradiol and testosterone to determine whether the presence of these hormones during molting modified the spectrophotometric characteristics of the plumage. No significant differences were found between treatments and controls in the colorimetric variables hue, ultraviolet saturation, and brightness. Similarly, the avian visual model showed no perceptible changes in chromatic and achromatic signals in the individual male adults. We also analyzed the effects of estrogen and testosterone on the growth speed of the new feathers. The hormone-treated groups increased in the speed of molting compared to the control group. These results suggest that the Eared Dove is an exception to basal branch models: rather than regulating coloration, sex hormones speed up the growth of the new feathers.

Cytokinins regulate spatially specific ethylene production to control root growth in Arabidopsis

Two principal growth regulators, cytokinins and ethylene, are known to interact in the regulation of plant growth. However, information about the underlying molecular mechanism and positional specificity of cytokinin/ethylene crosstalk in the control of root growth is scarce. We have identified the spatial specificity of cytokinin-regulated root elongation and root apical meristem (RAM) size, both of which we demonstrate to be dependent on ethylene biosynthesis. Upregulation of the cytokinin biosynthetic gene ISOPENTENYLTRANSFERASE (IPT) in proximal and peripheral tissues leads to both root and RAM shortening. By contrast, IPT activation in distal and inner tissues reduces RAM size while leaving the root length comparable to that of mock-treated controls. We show that cytokinins regulate two steps specific to ethylene biosynthesis: production of the ethylene precursor 1-aminocyclopropane-1-carboxylate (ACC) by ACC SYNTHASEs (ACSs) and its conversion to ethylene by ACC OXIDASEs (ACOs). We describe cytokinin- and ethylene-specific regulation controlling the activity of ACSs and ACOs that are spatially discrete along both proximo/distal and radial root axes. Using direct ethylene measurements, we identify ACO2, ACO3, and ACO4 as being responsible for ethylene biosynthesis and ethylene-regulated root and RAM shortening in cytokinin-treated Arabidopsis. Direct interaction between ARABIDOPSIS RESPONSE REGULATOR 2 (ARR2), a member of the multistep phosphorelay cascade, and the C-terminal portion of ETHYLENE INSENSITIVE 2 (EIN2-C), a key regulator of canonical ethylene signaling, is involved in the cytokinin-induced, ethylene-mediated control of ACO4. We propose tight cooperation between cytokinin and ethylene signaling in the spatially specific regulation of ethylene biosynthesis as a key aspect of the hormonal control of root growth.

Personalized medicine in acromegaly: The ACROFAST study.

prospective trial (21 university hospitals) comparing the effectiveness and time-to control of two treatment protocols during 12 months: A) A personalized protocol in which first option were fgSRLs as monotherapy or in combination with pegvisomant or, pegvisomant as monotherapy depending on the short Acute Octreotide Test (sAOT) results, tumor T2 Magnetic Resonance (MRI) signal or immunostaining for E-cadherin and, B) A control group with treatment always started by fgSRLs and the other drugs included after demonstrating inadequate control. Eighty-five patients participated; 45 in the personalized and 40 in the control group. More patients in the personalized protocol achieved hormonal control compared to those in the control group (78% vs 53%, p < 0.05). Survival analysis revealed a hazard ratio for achieving hormonal control adjusted by age and sex of 2.53 (CI 1.30-4.80). Patients from personalized arm were controlled in a shorter period of time (p = 0.01). Personalized medicine is feasible using a relatively simple protocol and allows a higher number of patients achieving control in a shorter period of time.

Sex and gender differences in adverse events following influenza and COVID-19 vaccination

IntroductionActive and passive surveillance studies have found that a greater proportion of females report adverse events (AE) following receipt of either the COVID-19 or seasonal influenza vaccine compared to males. In a predominately young adult female population of healthcare workers, we sought to determine the intersection of biological sex and sociocultural gender differences in prospective active reporting of vaccine outcomes, which remains poorly characterized.MethodsThis cohort study enrolled Johns Hopkins Health System healthcare workers (HCWs) who were recruited from the mandatory annual fall 2019–2022 influenza vaccine and the fall 2022 COVID-19 bivalent vaccine campaigns. Vaccine recipients were enrolled the day of vaccination and AE surveys were administered two days post-vaccination for bivalent COVID-19 and influenza vaccine recipients. Data were collected regarding the presence of a series of solicited local and systemic AEs. Open-ended answers about participants’ experiences with AEs also were collected for the COVID-19 vaccine recipients.ResultsFemales were more likely to report local AEs after either influenza (OR = 2.28, p = 0.001) or COVID-19 (OR = 2.57, p = 0.008) vaccination compared to males, regardless of age or race. Males and females had comparable probabilities of reporting systemic AEs after either influenza (OR = 1.18, p = 0.552) or COVID-19 (OR = 0.96, p = 0.907) vaccination. Hormonal birth control use did not impact the rates of reported AEs following influenza vaccination among reproductive-aged female HCWs. Women reported more interruptions in their daily routine following COVID-19 vaccination than men and were more likely to seek out self-treatment. More women than men scheduled their COVID-19 vaccination before their days off in anticipation of AEs.ConclusionsOur findings highlight the need for sex- and gender-inclusive policies to inform more effective mandatory occupational health vaccination strategies. Further research is needed to evaluate the potential disruption of AEs on occupational responsibilities following mandated vaccination for healthcare workers, a predominately female population, and to more fully characterize the post-vaccination behavioral differences between men and women.

Vitamin D is involved in the regulation of Cl− uptake in zebrafish (Danio rerio)

Cl− is a major anion in the bodily fluids of vertebrates, and maintaining its homeostasis is essential for normal physiological functions. Fishes inhabiting freshwater (FW) passively lose body fluid ions, including Cl−, to the external environment because of the electrochemical gradient of ions across the body surface. Therefore, FW fishes have to actively absorb Cl− from the surroundings to maintain ion homeostasis in their bodily fluids. Hormonal control is vital for modulating ion uptake in fish. Vitamin D is involved in the regulation of Ca2+ uptake and acid secretion in fish. In the present study, we found that the levels of bioactive vitamin D, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), significantly increased in zebrafish embryos and adults after exposure to water containing low levels of Cl−. Moreover, the administration of 1α,25(OH)2D3 treatment (20 μg/L) in zebrafish embryos, and intraperitoneal (i.p.) injection of 1α,25(OH)2D3 (5 μg/kg body mass) in zebrafish adults, resulting the increased Cl− content in bodily fluid in zebrafish. Na+-Cl− cotransporter 2b (NCC2b) and Cl− channel 2c (CLC2c) are specifically expressed during Cl− uptake by ionocytes in zebrafish. Our results indicated that the mRNA and protein expression of NCC2b and CLC2c considerably increased in the zebrafish with exogenous 1α,25(OH)2D3 treatment. Additionally, exogenous 1α,25(OH)2D3 administration increased the number of NCC2b- and CLC2c-expressing cells in yolk skins of zebrafish embryos and the gill filaments of zebrafish adults. Transcript signals of vitamin D receptors (VDRs) were identified in NCC2b-expressing cells. Knockdown of VDRa and VDRb significantly reduced the expression of NCC2b and CLC2c and the number of NCC2b- and CLC2c-expressing cells. These results indicate that vitamin D can affect Cl− uptake in zebrafish and extend our knowledge of the role of vitamin D in fish physiology.

The Protective Role of Magnoliae Flos in Preventing Ovotoxicity and Managing Ovarian Function: An In Vitro and In Vivo Study.

Magnoliae Flos (MF) is a medicinal herb widely employed in traditional medicine for relieving sinusitis, allergic rhinitis, headaches, and toothaches. Here, we investigated the potential preventive effects of MF extract (MFE) against 4-vinylcyclohexene diepoxide (VCD)-induced ovotoxicity in ovarian cells and a mouse model of premature ovarian insufficiency (POI). The cytoprotective effects of MFE were assessed using CHO-K1 or COV434 cells. In vivo, B6C3F1 female mice were intraperitoneally injected with VCD for two weeks to induce POI, while MFE was orally administered for four weeks, beginning one week before VCD administration. VCD led to a significant decline in the viabilities of CHO-K1 and COV434 cells and triggered excessive reactive oxygen species (ROS) production and apoptosis specifically in CHO-K1 cells. However, pretreatment with MFE effectively prevented VCD-induced cell death and ROS generation, while also activating the Akt signaling pathway. In vivo, MFE increased relative ovary weights, follicle numbers, and serum estradiol and anti-Müllerian hormone levels versus controls under conditions of ovary failure. Collectively, our results demonstrate that MFE has a preventive effect on VCD-induced ovotoxicity through Akt activation. These results suggest that MFE may have the potential to prevent and manage conditions such as POI and diminished ovarian reserve.

Anti-COVID-19 Vaccination Alters the Menstrual Cycle and Dose Accumulation Enhances the Effect.

Background and Objectives: New investigations have detected an enhanced probability for women to develop menstrual cycle alterations after anti-COVID-19 vaccination. Moreover, given that the protective immunity provided by anti-COVID-19 vaccination appears to wane quickly, booster vaccination has been recommended. Nonetheless, whether adverse events arise from such repeated immunization has not been studied. Materials and Methods: We studied the incidence of menstrual cycle alterations, the quantity of menstrual cycle alterations per subject, and of altered menstrual cycles in nonpregnant women of fertile age after anti-COVID-19 vaccination in a cohort of vaccinated female subjects by the means of a standardized questionary that was applied via telephone calls each month. Subjects that received up to four doses were studied for 6 months after each dose. We calculated the odds ratio for enhanced incidence, as well as quadratic functions for the tendencies. A sensitivity analysis excluding subjects taking hormonal birth control and those with polycystic ovary syndrome was performed. Results: Anti-COVID-19 vaccination enhanced the probability to develop menstrual cycle alterations (OR 1.52, CI at 95% 1.2-1.8, p < 0.0001) and, interestingly, such a tendency was enhanced when subjects received more doses (R2 = 0.91). Furthermore, the same trends repeated for the quantity of alterations per subject, and of altered cycles. Such an effect was further demonstrated to be independent upon the vaccine brand being applied, the birth control status, and the diagnosis of polycystic ovary syndrome. Conclusions: Vaccination is the most cost-effective measure for primary prevention and is considered to be safe. Nonetheless, in this article, we show data that suggest that repeated vaccination of adult female subjects may lead to an enhanced incidence of menstrual cycle-related adverse events, quantity of alterations per subject, and altered cycles. We therefore think that the development of new vaccine formulations that produce longer-lasting immunity is of paramount importance to reduce the potential for dose accumulation-dependent enhanced risk.