Hormonal Manipulation Research Articles

VmSpm1: a secretory protein from Valsa mali that targets apple's abscisic acid receptor MdPYL4 to suppress jasmonic acid signaling and enhance infection.

Pathogenic fungi such as Valsa mali secrete effector proteins to manipulate host defenses and facilitate infection. Subtilases are identified as potential virulence factors, yet their specific roles in fruit tree pathogens, such as those affecting apple trees, are poorly understood. Our research shows VmSpm1 as a virulence factor in V. mali. Knocking it out decreased virulence, whereas its heterologous expression in apple led to reduced disease resistance. Using Y2H, BiFC, SLC, and Co-IP techniques, we demonstrated an interaction between VmSpm1 and MdPYL4. MdPYL4 levels increased during V. mali infection. The stable transgenic apple lines inoculation experiment showed that MdPYL4 correlates with enhanced resistance to Apple Valsa canker when overexpressed in apples. Furthermore, through in vitro and in vivo assays, we showed the degradative role of VmSpm1 on MdPYL4. MdPYL4 promotes the synthesis of jasmonic acid (JA) in apples in an abscisic acid-dependent manner. The degradation of MdPYL4 leads to a reduction in JA content in apples during V. mali infection, thereby impairing JA signal transduction and decreasing disease resistance in apple plants. In summary, this study reveals how V. mali utilizes VmSpm1 to subvert JA signaling, shedding light on fungal manipulation of plant hormones to disrupt immunity.

Estrogen receptor α regulates the IKKs/NF-kB activity involved in the development of mechanical allodynia induced by REM sleep deprivation in rats

Several signaling pathways that converge in NF-kB activation have been linked to developing and maintaining different types of pathological pain. In addition, some mechanisms implied in the establishment of chronic pain have been demonstrated to have a sex-dependent correlation. This study aimed to determine if the IKKs/NF-kB signaling pathway is involved in establishing REM sleep deprivation (REMSD) induced mechanical allodynia in rats and its possible regulation depending on estradiol and estrogen receptors. Intrathecal administration of BMS-345541 or minocycline, two drugs that reduce the IKKs/NF-kB activity, avoided the development of mechanical allodynia in female but not in male rats subjected to 48 h of REMSD. Ovariectomy in female rats abolished the effect of BMS-345541 and minocycline. Meanwhile, the 17-β-estradiol restitution restored it. Intrathecal administration of MPP, a selective ERα antagonist, but not PHTPP, a selective ERβ antagonist, avoided the effect of BMS-345541 in female rats without hormonal manipulation. In addition, the transient run-down of ERα in female rats abolished the effect of BMS-345541. All data suggest an important role of ERα as a regulator of the IKKs/NF-kB activity. REMSD increased the ERα protein expression in the dorsal root ganglia and the dorsal spinal cord in females but not in male rats. Interestingly, ERα activation or ERα overexpression allowed the effect of BMS-345541 in male rats. Data suggest an important regulatory role of ERα in the IKKs/NF-kB activity on establishing mechanical allodynia induced by REMSD in female rats.

Role of Platelet-Rich Plasma in the Management of Non-obstructive Azoospermia.

Non-obstructive azoospermia (NOA) is a common cause of infertility in males, which is characterized by the absence of sperm in the ejaculate, resulting from impaired spermatogenesis. The primary therapeutic approaches for the management of NOA include testicular sperm extraction, varicocelectomy in case of clinical varicoceles, and hormonal manipulation. While traditional treatments are found to have a limited role in the management of NOA, recent studies have explored the potential of platelet-rich plasma (PRP) as a safer and promising therapeutic option. Autologous PRP preparations are derived from the patient's blood and comprise growth factors and cytokines, promoting tissue repair and regeneration. PRP has a wide range of applications in the medical field, including managing infertility in males and females. This literature review aimed to evaluate the existing evidence on the efficacy and safety of PRP in the management of NOA. After a thorough review of relevant data from observational and experimental studies, the findings of this study suggested that PRP may positively influence spermatogenesis, sperm quality, DNA integrity, and sperm retrieval during assisted reproductive procedures. Further research is needed to establish the optimal PRP preparation, administration method, and long-term benefits. The newer studies shall include a diverse patient population and employ long-term follow-up to assess the durability of any positive effects of PRP treatment. The growing body of evidence regarding the therapeutic potential for NOA in humans offers greater opportunities for men seeking fertility treatment, informing clinical practice, and optimizing the use of PRP.

Manipulating hormones to mitigate trade-offs in crops.

Summary statementAddressing trait coupling due to gene pleiotropy presents challenges in conventional breeding system. However, targeted hormonal manipulation and precise genetic engineering designs hold promise to alleviate trade‐offs and unlock the potential of crops for multiple desirable traits.

Prostate cancer in transgender women: A propensity score-matched analysis of disease severity and survival.

Despite the rise in gender-affirming care, our understanding of prostate cancer (PCa) in transgender women (TGW) remains in its infancy. Health disparities and lack of PCa awareness and screening are possible barriers to providing quality care for this population. In addition, the implication of hormonal manipulation for the aggressiveness of PCa in TGW is yet to be determined. Here, this study sought to compare oncological characteristics and survival outcomes between transgender and cisgender (CG) patients with PCa via two national data sets. The Veterans Affairs Informatics and Computing Infrastructure database (1999-2020) and the Surveillance, Epidemiology, and End Results-Medicare database (2010-2017) were reviewed. Demographic and clinical details were analyzed. Logistic regression analysis was performed on propensity score-matched groups to identify predictors of high-risk disease and metastasis in patients with PCa. Groups were matched 5:1 (CG:TGW) on the basis of age, race, year of diagnosis, and Charlson Comorbidity Index score. Primary outcomes included metastatic presentation, high-risk localized disease, overall survival (OS), and prostate cancer-specific mortality (PCSM). A total of 1194 patients were included (199 TGW; 995 CG). Associations between transgender identity and metastatic presentation (odds ratio [OR], 0.38; p=.2), high-risk localized disease (OR, 1.19; p=.50), or PCSM (hazard ratio [HR], 0.65; p=.3) were not detected. Transgender identity was associated with improved OS (HR,0.67; p=.014). PCa-specific outcomes seem comparable between TGW and CG men, although the study was underpowered to detect modest differences. Further investigation into the incidence and outcomes of PCa in TGW is warranted.

Sex- and caste-specific developmental responses to juvenile hormone in an ant with maternal caste determination.

Juvenile hormone is considered to be a master regulator of polyphenism in social insects. In the ant Cardiocondyla obscurior, whether a female egg develops into a queen or a worker is determined maternally and caste-specific differentiation occurs in embryos, so that queens and workers can be distinguished in a non-invasive manner from late embryogenesis onwards. This ant also exhibits two male morphs - winged and wingless males. Here, we used topical treatment with juvenile hormone III and its synthetic analogue methoprene, a method that influences caste determination and differentiation in some ant species, to investigate whether hormone manipulation affects the development and growth of male, queen- and worker-destined embryos and larvae. We found no effect of hormone treatment on female caste ratios or body sizes in any of the treated stages, even though individuals reacted to heightened hormone availability with increased expression of krüppel-homolog 1, a conserved JH first-response gene. In contrast, hormone treatment resulted in the emergence of significantly larger males, although male morph fate was not affected. These results show that in C. obscurior, maternal caste determination leads to irreversible and highly canalized caste-specific development and growth.

CLINICAL PRESENTATIONS AND SURGICAL MANAGEMENT OF UTERINE SEPTUM-ASSOCIATED INFERTILITY: A CASE SERIES STUDY

Uterine septum, a congenital uterine anomaly, is implicated in female infertility and adverse reproductive outcomes. This retrospective descriptive case series examines eight patients treated for primary or secondary infertility associated with uterine septum. Diagnostic evaluations, surgical interventions, and postoperative outcomes are presented. Hysteroscopic septum resection emerged as the primary surgical intervention, with varying success rates in achieving pregnancy postoperatively. Factors influencing outcomes include patient age, septum morphology, and associated comorbidities. Individualized treatment strategies and adjunctive therapies such as hormonal manipulation and assisted reproductive techniques are crucial for optimizing fertility outcomes. While promising, long-term reproductive prognosis post-surgery remains uncertain, warranting further research and prospective studies. This study underscores the complexity of uterine septum-associated infertility and emphasizes the need for a multidisciplinary approach to management, aiming to enhance reproductive outcomes and fulfill the reproductive aspirations of affected individuals.

Refuting Six Misconceptions about Romantic Love.

Scientific research on romantic love has been relatively sparse but is becoming more prevalent, as it should. Unfortunately, several misconceptions about romantic love are becoming entrenched in the popular media and/or the scientific community, which hampers progress. Therefore, I refute six misconceptions about romantic love in this article. I explain why (1) romantic love is not necessarily dyadic, social, or interpersonal, (2) love is not an emotion, (3) romantic love does not just have positive effects, (4) romantic love is not uncontrollable, (5) there is no dedicated love brain region, neurotransmitter, or hormone, and (6) pharmacological manipulation of romantic love is not near. To increase progress in our scientific understanding of romantic love, I recommend that we study the intrapersonal aspects of romantic love including the intensity of love, that we focus our research questions and designs using a component process model of romantic love, and that we distinguish hypotheses and suggestions from empirical findings when citing previous work.

Abstract ED01-01: Optimizing endocrine therapy in premenopausal women

Abstract Premenopausal women with early-stage hormone receptor (HR)-positive breast cancer are candidates for adjuvant endocrine therapy and have several treatment options. The clinical team should assess an individual woman’s risk of recurrence, estimate benefits from specific endocrine manipulations, and consider co-morbidities, adverse event profile and host factors. Risk stratification strategies including clinic-pathologic features, genomic assays and composite scores can guide recommendations regarding type and duration of endocrine therapy, in particular in node-negative disease. Adjuvant tamoxifen for 5 to 10 years significantly reduces breast cancer recurrence and death. Premenopausal women who are at high risk of recurrence benefit from ovarian function suppression (OFS) with tamoxifen or an aromatase inhibitor for 5 years. Those include women with high-risk clinico-pathological features and younger age, and for whom chemotherapy is commonly recommended. There are currently no available data regarding the use of extended OFS beyond 5 years. Newer data support the addition of CDK 4/6 inhibitors to endocrine therapy in women with high-risk disease. Endocrine therpay is associated with frequent bothersome and few significant side effects that can negatively impact quality of life and adherence to treatment. Clinicians must carefully weigh the benefits associated with specific endocrine therapies, and possible short- and long-term side effects to individualize therapy, and to consider interventions to enhance adherence. Citation Format: V. Stearns. Optimizing endocrine therapy in premenopausal women [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr ED01-01.

A Comprehensive Review and Androgen Deprivation Therapy and Its Impact on Alzheimer's Disease Risk in Older Men with Prostate Cancer.

Prostate cancer (PCa) is one of the most prevalent malignancies affecting males worldwide. Despite reductions in mortality rates due to advances in early identification and treatment methods, PCa remains a major health concern. Recent research has shed light on a possible link between PCa and Alzheimer's disease (AD), which is a significant neurological ailment that affects older males all over the world. Androgen deprivation therapy (ADT), a cornerstone therapeutic method used in conjunction with radiation and palliative care in advanced metastatic PCa cases, is critical for disease management. Evidence reveals a relationship between ADT and cognitive impairment. Hormonal manipulation may cause long-term cognitive problems through processes such as amyloid beta (Aβ) aggregation and neurofibrillary tangles (NFTs). Fluctuations in basal androgen levels can upset the delicate balance of genes that are sensitive to androgen levels, contributing to cognitive impairment. This detailed review dives into the various aspects of PCa aetiology and its relationship with cognitive decline. It investigates the discovery of particular biomarkers, as well as microRNAs (miRNAs), which play important roles in pathogenic progression. The review attempts to identify potential biomarkers associated with ADT-induced cerebral changes, including Aβ oligomer buildup, NFT formation, and tauopathy, which can contribute to early-onset dementia and cognitive impairment. Besides it further aims to provide insights into innovative diagnostic and therapeutic avenues for alleviating PCa and ADT-related cognitive sequelae by unravelling these complicated pathways and molecular mechanisms.

Divergent NMJ Development Supports Female Vocal Suppression in the Zebra Finch Songbird (Taeniopygia guttata)

Songbirds have long been central to the study of vocal learning and production, and in most species, males and females sing. However, in the best-studied species, the zebra finch ( Taeniopygia guttata), only males sing. Most theories of this sexual dimorphism had suggested that male zebra finches have specializations, e.g. to promote song, that females do not. We recently found the opposite. At the synapses that connect motoneurons to muscle fibers (neuromuscular junctions; NMJs) of the avian voicebox (syrinx, analogous to larynx), we found female synaptic specializations that support song suppression: Female syrinx, and only female syrinx (not tongue, latissimus dorsi, or any male muscle measured) has specialized NMJs that could work to suppress singing ability in this species. Specifically, the female syrinx shows a high proportion of putatively weaker en grappe NMJs, biased towards smaller and weaker muscle fibers, which fail to form a motor endplate band (MEB). However, these results raise an unanswered question: are male and female syringes born differently, or do they have divergent developmental programs? We analyzed males and females (n=3) across critical ages - the robust onset of sensory song learning (post-hatch day P30), song-like vocalizations (P50), and the end of sensorimotor learning (P70). We find that NMJs in male and female syrinx muscles are similar early in development and diverge around the age that vocal behavior becomes sexually dimorphic, approaching their different adult phenotypes by the end of this learning phase. We find that outside the MEB, en grappe NMJs are pruned away in males, while en plaque NMJs are lost here in females. Additionally, these NMJ features are highly labile in development, as there are many examples of NMJs intermediate between the vertebrate-typical en plaque and the less well-described en grappe, implying some transitory nature of NMJ class. Preliminary work using developmental hormonal manipulations, which induces sex-reversal of vocal behavior (i.e., promoting female song, or suppressing male song), indicates the en grappe NMJs specifically outside the MEB are most directly tied to vocal ability. Interestingly, the songbird syrinx lacks the tonic muscle fibers on which en grappe NMJs are typically found in mammals, opening the question of the functional attributes of these NMJs. Future work aims to characterize the physiological properties of these putatively weaker synapses, as well as their functional consequences to vocal sexual dimorphism. NSF-GRFP awarded to JVG; Neuronex awarded to NBK. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Gender and kidney transplantation.

Kidney transplantation provides the best form of kidney replacement therapy with improvement in quality of life and longevity. However, disparity exists in its availability, utilisation and outcomes, not only due to donor availability or financial constraints but also arising from the influence of biological sex and its sociocultural attribute i.e., Gender. Women make up the majority of kidney donors but are less likely to be counselled regarding transpantation, be waitlisted or receive living/deceased donor kidney. Biological differences also contribute to differences in kidney transplantation among the sexes. Women are more likely to be sensitised owing to pregnancy, especially in multiparous individuals, complicating donor compatibility. A heightened immune system in women, evidenced by more autoimmune illnesses, increases the risk of allograft rejection and loss. Differences in the pharmacokinetics of transplant drugs owing to biological variances could also contribute to variability in outcomes. Transgender medicine is also increasingly becoming a relevant topic of study, providing greater challenges in the form of hormonal manipulations and anatomic changes. It is thus important to determine and study transplantation and its nuances in this backdrop to be able to provide relevant sex and gender-specific interventions and design better practices for optimum kidney transplant utilisation and outcomes.

Comprehensive Review on Recent Strategies for Management of Prostate Cancer: Therapeutic Targets and SAR.

Prostate cancer is a disease that is affecting a large population worldwide. Androgen deprivation therapy (ADT) has become a foundation for the treatment of advanced prostate cancer, as used in most clinical settings from neo-adjuvant to metastatic stage. In spite of the success of ADT in managing the disease in the majority of men, hormonal manipulation fails eventually. New molecules are developed for patients with various hormone-refractory diseases. Advancements in molecular oncology have increased understanding of numerous cellular mechanisms which control cell death in the prostate and these insights can lead to the development of more efficacious and tolerable therapies for carcinoma of the prostate. This review is focused on numerous therapies that might be a boon for prostate therapy like signaling inhibitors, vaccines, and inhibitors of androgen receptors. Along with these, various bioactive molecules and their derivatives are highlighted, which act as potential antiprostate cancer agents. This article also emphasized the recent advances in the field of medicinal chemistry of prostate cancer agents.

The impact of estradiol on serotonin, glutamate, and dopamine systems.

Estradiol, the most potent and prevalent member of the estrogen class of steroid hormones and is expressed in both sexes. Functioning as a neuroactive steroid, it plays a crucial role in modulating neurotransmitter systems affecting neuronal circuits and brain functions including learning and memory, reward and sexual behaviors. These neurotransmitter systems encompass the serotonergic, dopaminergic, and glutamatergic signaling pathways. Consequently, this review examines the pivotal role of estradiol and its receptors in the regulation of these neurotransmitter systems in the brain. Through a comprehensive analysis of current literature, we investigate the multifaceted effects of estradiol on key neurotransmitter signaling systems, namely serotonin, dopamine, and glutamate. Findings from rodent models illuminate the impact of hormone manipulations, such as gonadectomy, on the regulation of neuronal brain circuits, providing valuable insights into the connection between hormonal fluctuations and neurotransmitter regulation. Estradiol exerts its effects by binding to three estrogen receptors: estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), and G protein-coupled receptor (GPER). Thus, this review explores the promising outcomes observed with estradiol and estrogen receptor agonists administration in both gonadectomized and/or genetically knockout rodents, suggesting potential therapeutic avenues. Despite limited human studies on this topic, the findings underscore the significance of translational research in bridging the gap between preclinical findings and clinical applications. This approach offers valuable insights into the complex relationship between estradiol and neurotransmitter systems. The integration of evidence from neurotransmitter systems and receptor-specific effects not only enhances our understanding of the neurobiological basis of physiological brain functioning but also provides a comprehensive framework for the understanding of possible pathophysiological mechanisms resulting to disease states. By unraveling the complexities of estradiol's impact on neurotransmitter regulation, this review contributes to advancing the field and lays the groundwork for future research aimed at refining understanding of the relationship between estradiol and neuronal circuits as well as their involvement in brain disorders.

Phytohormones-mediated strategies for mitigation of heavy metals toxicity in plants focused on sustainable production.

In this manuscript, authors reviewed and explore the information on beneficial role of phytohormones to mitigate adverse effects of heavy metals toxicity in plants. Global farming systems are seriously threatened by heavy metals (HMs) toxicity, which can result in decreased crop yields, impaired food safety, and negative environmental effects. A rise in curiosity has been shown recently in creating sustainable methods to reduce HMs toxicity in plants and improve agricultural productivity. To accomplish this, phytohormones, which play a crucial role in controlling plant development and adaptations to stress, have emerged as intriguing possibilities. With a particular focus on environmentally friendly farming methods, the current review provides an overview of phytohormone-mediated strategies for reducing HMs toxicity in plants. Several physiological and biochemical activities, including metal uptake, translocation, detoxification, and stress tolerance, are mediated by phytohormones, such as melatonin, auxin, gibberellin, cytokinin, ethylene, abscisic acid, salicylic acid, and jasmonates. The current review offers thorough explanations of the ways in which phytohormones respond to HMs to help plants detoxify and strengthen their resilience to metal stress. It is crucial to explore the potential uses of phytohormones as long-term solutions for reducing the harmful effects of HMs in plants. These include accelerating phytoextraction, decreasing metal redistribution to edible plant portions, increasing plant tolerance to HMs by hormonal manipulation, and boosting metal sequestration in roots. These methods seek to increase plant resistance to HMs stress while supporting environmentally friendly agricultural output. In conclusion, phytohormones present potential ways to reduce the toxicity of HMs in plants, thus promoting sustainable agriculture.

Gender minorities in breast cancer – Clinical trials enrollment disparities: Focus on male, transgender and gender diverse patients

BackgroundThe last years have seen unprecedented improvement in breast cancer (BC) survival rates. However, this entirely apply to female BC patients, since gender minorities (male, transgender/gender-diverse) are neglected in BC phase III registration clinical trials. MethodsWe conducted a scoping review of phase III clinical trials of agents with a current positioning within the therapeutic algorithms of BC. ResultsWe selected 51 phase III trials. Men enrollment was allowed in 35.3% of trials. In none of the trial inclusion/exclusion criteria referred to transgender/gender-diverse people. A numerical higher rate of enrolled men was observed in the contemporary as compared to historical group.We found a statistically significant association between the drug class and the possibility of including men: 100%, 80%, 50%, 33.3%, 25%, 10% and 9.1% of trials testing ICI/PARP-i, ADCs, PI3K/AKT/mTOR-i, anti-HER2 therapy, CDK4/6-i, ET alone, and CT alone.Overall, 77409 patients were enrolled, including 112 men (0.2%). None of the trial reported transgender/gender-diverse people proportion. Studies investigating PARP-i were significantly associated with the highest rate of enrolled men (1.42%), while the lowest rates were observed for trials of CT (0.13%), ET alone (0.10%), and CDK 4/6-I (0.08%), p < 0.001. ConclusionsWe confirmed that gender minorities are severely underrepresented among BC registration trials. We observed a lower rate of men in trials envisaging endocrine manipulation or in less contemporary trials. This work sought to urge the scientific community to increase the awareness level towards the issue of gender minorities and to endorse more inclusive criteria in clinical trials.

Enhancing rice panicle branching and grain yield through tissue-specific brassinosteroid inhibition.

Crop yield potential is constrained by the inherent trade-offs among traits such as between grain size and number. Brassinosteroids (BRs) promote grain size, yet their role in regulating grain number is unclear. By deciphering the clustered-spikelet rice germplasm, we show that activation of the BR catabolic gene BRASSINOSTEROID-DEFICIENT DWARF3 (BRD3) markedly increases grain number. We establish a molecular pathway in which the BR signaling inhibitor GSK3/SHAGGY-LIKE KINASE2 phosphorylates and stabilizes OsMADS1 transcriptional factor, which targets TERMINAL FLOWER1-like gene RICE CENTRORADIALIS2. The tissue-specific activation of BRD3 in the secondary branch meristems enhances panicle branching, minimizing negative effects on grain size, and improves grain yield. Our study showcases the power of tissue-specific hormonal manipulation in dismantling the trade-offs among various traits and thus unleashing crop yield potential in rice.

(244) Optimization of Sperm Retrieval in Non-Obstructive Azoospermic Patients using Conventional TESE

Abstract Introduction Sperm retrieval in NOA patients remain to be the only hope for these patients for fatherhood using assisted reproductive techniques. Micro-TESE is the gold standard with the best retrieval rate. Microsurgical facilities are not available at every center and conventional TESE techniques are not standardized between different centers. Objective Our aim is To improve the spermatogenic function of NOA patients to enable the appearance of sperm in their ejaculate or to improve the chances of a successful retrieval from the testis for ICSI and To optimize and standardize our conventional TESE technique Methods Over last 7 years 94 cases of NOA patients were subjected to conventional TESE. We Exclude the cases of Obstructive Azoospermia, Cases with abnormal chromosomal analysis were referred for higher center for genetic counselling and diagnosis. Laboratory workup including at least two semen samples, hormonal valuation (FSH, LH, Prolactin, Testosterone) and chromosomal analysis (Karyotyping and Testing for Y chromosome micro-deletions. Pre-TESE medical Treatment: included Clomiphene citrate: 50 mg OD for 3–6 months, Anti-oxidant therapy (Vitamin E 200mg BID and Vitamin C, 1 gm, OD). 6 biopsies from each testis: upper pole 2(medial &amp;Lateral), mid zone 2 (medial &amp; Lateral), lower pole 2(medial &amp;Lateral). Separate biopsy from each testis was sent for definitive histopathological correlation. Experienced embryologist attends each procedure examining each biopsy until sperms are retrieved. Samples taken were centrifuged and re-examined at lab for any missed sperm Results sperm retrieval was successful in 38patients (40.4%). All cases were done as day case No single case of wound infection or intra-testicular hematoma.Post-operative pain was tolerable and managed by paracetamol ±NSAID Negative cases for sperms were continued on higher dose of CC and referred for microTESE Conclusions Though of low-evidence, empiric Pre-TESE enhancement of spermatogenesis should be attempted whenever possible and after proper patients counselling. This systematic anatomical approach for biopsies yielded high SRR compared to other conventional TESE. Exact localization of + ve testicular site and side If patient needed Re-do TESE for more sperms in the future. Although micro TESE remains to be the best modality for SR in NOA, in our hands and in canters without Micro-TESE facilities, applying this standardized technique with pre-operative hormonal manipulation yields accepted rate of sperm retrieval Disclosure No.

Abstract 1101 Enhancing the reproductive capacity of female blue swimming crabs, Portunus pelagicus through hormonal manipulation and its potential for implementation in aquaculture

Abstract 1101 Enhancing the reproductive capacity of female blue swimming crabs, Portunus pelagicus through hormonal manipulation and its potential for implementation in aquaculture

The Estrogen Receptor Alpha Regulates the Sex-dependent Expression and Pronociceptive Role of Bestrophin-1 in Neuropathic Rats

Bestrophin-1, a calcium-activated chloride channel (CaCC), is involved in neuropathic pain; however, it is unclear whether it has a dimorphic role in female and male neuropathic rats. This study investigated if 17β-estradiol and estrogen receptor alpha (ERα) activation regulate bestrophin-1 activity and expression in neuropathic rats. Neuropathic pain was induced by L5-spinal nerve transection (SNT). Intrathecal administration of CaCCinh-A01 (.1–1 µg), a CaCC blocker, reversed tactile allodynia induced by SNT in female but not male rats. In contrast, T16Ainh-A01, a selective anoctamin-1 blocker, had an equal antiallodynic effect in both sexes. SNT increased bestrophin-1 protein expression in injured L5 dorsal root ganglia (DRG) in female rats but decreased bestrophin-1 protein in L5 DRG in male rats. Ovariectomy prevented the antiallodynic effect of CaCCinh-A01, but 17β-estradiol replacement restored it. The effect of CaCCinh-A01 was prevented by intrathecal administration of MPP, a selective ERα antagonist, in rats with and without prior hormonal manipulation. In female rats with neuropathy, ovariectomy prevented the increase in bestrophin-1 and ERα protein expression, while 17β-estradiol replacement allowed for an increase in both proteins in L5 DRG. Furthermore, ERα antagonism (with MPP) prevented the increase in bestrophin-1 and ERα protein expression. Finally, ERα activation with PPT, an ERα selective activator, induced the antiallodynic effect of CaCCinh-A01 in neuropathic male rats and prevented the reduction in bestrophin-1 protein expression in L5 DRG. In summary, data suggest ERα activation is necessary for bestrophin-1’s pronociceptive action to maintain neuropathic pain in female rats. PerspectiveThe mechanisms involved in neuropathic pain differ between male and female animals. Our data suggest that ERα is necessary for expression and function of bestrophin-1 in neuropathic female but not male rats. Data support the idea that a therapeutic approach to relieving neuropathic pain must be based on patient's gender.