Sex Steroids Research Articles

Cellular and Molecular Effects of Steroid Sex Hormones on the Vocal Folds: A Scoping Review.

Steroid sex hormones (SSH) target cell nuclei to affect transcription. Although laryngeal tissue is theorized to be hormonally responsive, SSH receptor presence and cellular effects on the vocal folds are not well-established. A scoping review of this literature might inform future research. Medline, Embase, Scopus, and Web of Science were searched. This review followed JBI and PRISMA-ScR Guidelines. Two independent reviewers screened each title/abstract and full text according to eligibility criteria. Exclusion criteria included primary outcomes based on subjective interpretation and secondary effects on the vocal folds (e.g., voice). Three hundred and sixtyone articles were screened at the title/abstract level, 83 at the full-text level, and 32 met inclusion criteria. Fourteen studies were performed in humans and 15 in animals; 3 were review articles. In studies directly examining receptors (n = 17), estrogen receptors (ER) were found in 10 of 15 studies, progesterone receptors (PR) in 6/10, and androgen receptors (AR) in 6/9. When the effects of SSH on vocal folds were studied (n = 16), estrogen had effects in 10/13, progesterone in 3/3, and androgens in 4/5. ER and PR were mostly identified in epithelium and fibroblasts of lamina propria (LP) while AR was found in muscle, lamina propria, and epithelium. Existing evidence variably supports the presence of SSH receptors in vocal fold tissue; therefore, further clarification is needed. Estrogen and progesterone were most identified in mucosal tissue, where they decrease fibrosis and help maintain the epithelial barrier. Androgens appear to be pro-fibrotic in epithelium and hypertrophic in muscle. Laryngoscope, 2024.

Uterine cyclin A2 deficient mice as a model of female early pregnancy loss.

Proper action of the female sex steroids, 17β-estradiol (E2) and progesterone (P4) on endometrium is essential for fertility. Beyond its role in regulating the cell cycle, cyclin A2 (CCNA2) also mediates E2 and P4 signaling in vitro, but a potential role in modulating steroid action for proper endometrial tissue development and function is unknown. To fill this gap in our knowledge, we examined human endometrial tissue from fertile and infertile women for CCNA2 expression and correlated this with pregnancy outcome. Functional assessment of CCNA2 was validated in vivo using a conditional Ccna2 uterine deficient mouse model while in vitro function was assessed using human cell culture models. We found that CCNA2 expression was significantly reduced in endometrial tissue, specifically the stromal cells, from women undergoing in vitro fertilization who failed to achieve pregnancy. Conditional deletion of Ccna2 from mouse uterine tissue resulted in an inability to achieve pregnancy which appears to be due to alterations in the process of decidualization, which was confirmed using in vitro models. From these studies, we conclude that CCNA2 expression during the proliferative/regenerative stage of the menstrual cycle acts as a safeguard allowing for proper steroid responsiveness, decidualization and pregnancy. When CCNA2 expression levels are insufficient there is impaired endometrial responsiveness, aberrant decidualization and loss of pregnancy.

Identification of candidate genes and pathways involved in the establishment of sexual size dimorphism in the olive flounder (Paralichthys olivaceus) using RNA-seq

Olive flounder (Paralichthys olivaceus) is a valuable mariculture fish that shows female-biased sexual size dimorphism (SSD), yet the molecular mechanisms responsible for this phenomenon remain poorly understood. In this study, the growth differences between females and males were compared, and comparative transcriptome analyses of brains/pituitaries, livers, muscles, and gonads from 13-month-old females and males were performed. The critical time window for SSD was from 13- to 14-month-old, with females reaching significantly larger sizes than males. Muscle cell size and plasma growth hormone (GH), insulin-like growth factor 1 and 2 (IGF1, IGF2), 11-ketotestosterone (11-KT), and 17β-estradiol (E2) levels had no significant differences between the sexes of 13- and 14-month-old flounders. Furthermore, the RNA-seq data revealed differential expression in the genes encoding the receptors for these hormones, suggesting that regulation may occur at the receptor level, potentially leading to SSD during the critical window. RNA-seq analysis identified 88, 645, 414, and 15,833 differentially expressed genes between females and males in brains/pituitaries, livers, muscles, and gonads, respectively. KEGG (Kyoto Encyclopedia of Genes and Genomes) and GSEA-based KEGG analyses revealed that some pathways associated with growth and development, including “prolactin signaling pathway” in brains/pituitaries, “cell cycle”, “oocyte meiosis”, and “DNA replication” in livers, “focal adhesion”, “ECM-receptor interaction”, “protein digestion and absorption”, “arginine and proline metabolism”, and “cysteine and methionine metabolism” in muscles, and “Hippo signaling pathway” and “JAK-STAT signaling pathway” in gonads may be involved in the establishment of sexual growth differences. Notably, females had lower steroid hormone synthesis abilities than males in brains/pituitaries, livers, and gonads, indicating the importance of sex steroid hormones in the establishment of SSD. Moreover, genes including frizzled3 (fzd3) and prolactin (prl) in brains/pituitaries, and growth hormone receptor (ghr), estrogen receptor (esr1), insulin-like growth factor binding protein-3 (igfbp3), bone morphogenetic protein 8A-like (bmp8a), leptin receptor (lepr), and lipoprotein lipase-like (lpl) in livers emerge as potential candidates for the establishment of SSD. In conclusion, this study may help clarify the molecular mechanisms involved in SSD-related growth traits in flounder and provide basic data for genetic breeding of flounder.

Histological observations and transcriptome analyses reveal the dynamic changes in the gonads of the blotched snakehead (Channa maculata) during sex differentiation and gametogenesis

BackgroundBlotched snakehead (Channa maculata) displays significant sexual dimorphism, with males exhibiting faster growth rates and larger body sizes compared to females. The cultivation of the all-male population of snakeheads holds substantial economic and ecological value. Nonetheless, the intricate processes governing the development of bipotential gonads into either testis or ovary in C. maculata remain inadequately elucidated. Therefore, it is necessary to determine the critical time window of sex differentiation in C. maculata, providing a theoretical basis for sex control in production practices.MethodsThe body length and weight of male and female C. maculata were measured at different developmental stages to reveal when sexual dimorphism in growth initially appears. Histological observations and spatiotemporal comparative transcriptome analyses were performed on ovaries and testes across various developmental stages to determine the crucial time windows for sex differentiation in each sex and the sex-related genes. Additionally, qPCR and MG2C were utilized to validate and locate sex-related genes, and levels of E2 and T were quantified to understand sex steroid synthesis.ResultsSexual dimorphism in growth became evident starting from 90 dpf. Histological observations revealed that morphological sex differentiation in females and males occurred between 20 and 25 dpf or earlier and 30–35 dpf or earlier, respectively, corresponding to the appearance of the ovarian cavity or efferent duct anlage. Transcriptome analyses revealed divergent gene expression patterns in testes and ovaries after 30 dpf. The periods of 40–60 dpf and 60–90 dpf marked the initiation of molecular sex differentiation in females and males, respectively. Male-biased genes (Sox11a, Dmrt1, Amh, Amhr2, Gsdf, Ar, Cyp17a2) likely play crucial roles in male sex differentiation and spermatogenesis, while female-biased genes (Foxl2, Cyp19a1a, Bmp15, Figla, Er) could be pivotal in ovarian differentiation and development. Numerous biological pathways linked to sex differentiation and gametogenesis were also identified. Additionally, E2 and T exhibited sexual dimorphism during sex differentiation and gonadal development. Based on these results, it is hypothesized that in C. maculata, the potential male sex differentiation pathway, Sox11a–Dmrt1–Sox9b, activates downstream sex-related genes (Amh, Amhr2, Gsdf, Ar, Cyp17a2) for testicular development, while the antagonistic pathway, Foxl2/Cyp19a1a, activates downstream sex-related genes (Bmp15, Figla, Er) for ovarian development.ConclusionsThis study provides a comprehensive overview of gonadal dynamic changes during sex differentiation and gametogenesis in C. maculata, establishing a scientific foundation for sex control in this species.

Association of phthalates exposure and sex steroid hormones with late-onset preeclampsia: a case-control study

BackgroundThis study aimed to investigate the relationship between phthalates exposure and estrogen and progesterone levels, as well as their role in late-onset preeclampsia.MethodsA total of 60 pregnant women who met the inclusion and exclusion criteria were recruited. Based on the diagnosis of preeclampsia, participants were divided into two groups: normotensive pregnant women (n = 30) and pregnant women with late-onset preeclampsia (n = 30). The major metabolites of phthalates (MMP, MEP, MiBP, MBP, MEHP, MEOHP, MEHHP) and sex steroid hormones (estrogen and progesterone) were quantified in urine samples of the participants.ResultsNo significant differences were observed in the levels of MMP, MEP, MiBP, MBP, MEHP, MEOHP, and MEHHP between women with preeclampsia and normotensive pregnant women (P > 0.05). The urinary estrogen showed a negative correlation with systolic blood pressure (rs= -0.46, P < 0.001) and diastolic blood pressure (rs= -0.47, P < 0.001). Additionally, the urinary estrogen and progesterone levels were lower in women with preeclampsia compared to those in normotensive pregnant women (P < 0.05). After adjusting for confounding factors, we observed a significant association between reduced urinary estrogen levels and an increased risk of preeclampsia (aOR = 0.09, 95%CI = 0.02–0.46). Notably, in our decision tree model, urinary estrogen emerged as the most crucial variable for identifying pregnant women at a high risk of developing preeclampsia. A positive correlation was observed between urinary progesterone and MEHP (rs = 0.36, P < 0.05) in normotensive pregnant women. A negative correlation was observed between urinary estrogen and MEP in pregnant women with preeclampsia (rs= -0.42, P < 0.05).ConclusionsPhthalates exposure was similar in normotensive pregnant women and those with late-onset preeclampsia within the same region. Pregnant women with preeclampsia had lower levels of estrogen and progesterone in their urine, while maternal urinary estrogen was negatively correlated with the risk of preeclampsia and phthalate metabolites (MEP).Trial registrationRegistration ID in Clinical Trials: NCT04369313; registration date: 30/04/2020.

Sex steroid hormone residues in milk and their potential risks for breast and prostate cancer.

Milk was a source of important nutrients for humans and was especially important for children and adolescents. The modern dairy animal production pattern had contributed to residual sex steroid hormones in milk. When this milk was consumed by humans, these hormones entered the body leading to hormonal disruptions and potentially increasing the risk of various types of cancers. This article reviewed the presence of residual sex steroid hormones in milk, their potential risks on human health, and their possible association with the incidence of breast and prostate cancer. The potential linkage between dairy consumption and these cancers were described in detail. The hormones present in dairy products could affect the development and progression of these types of cancer. Sex steroid hormones could interact with different signaling pathways, influencing carcinogenic cascades that could eventually lead to tumorigenesis. Given these potential health risks, the article suggested appropriate consumption of dairy products. This included being mindful not just of the amount of dairy consumed, but also the types of dairy products selected. More scientific exploration was needed, but this review provided valuable insights for health-conscious consumers and contributed to the ongoing discussion on dietary guidelines and human health.

Gender-affirming hormonal therapy induces a gender-concordant fecal metagenome transition in transgender individuals

BackgroundLimited data exists regarding gender-specific microbial alterations during gender-affirming hormonal therapy (GAHT) in transgender individuals. This study aimed to investigate the nuanced impact of sex steroids on gut microbiota taxonomy and function, addressing this gap. We prospectively analyzed gut metagenome changes associated with 12 weeks of GAHT in trans women and trans men, examining both taxonomic and functional shifts.MethodsThirty-six transgender individuals (17 trans women, 19 trans men) provided pre- and post-GAHT stool samples. Shotgun metagenomic sequencing was used to assess the changes in gut microbiota structure and potential function following GAHT.ResultsWhile alpha and beta diversity remained unchanged during transition, specific species, including Parabacteroides goldsteinii and Escherichia coli, exhibited significant abundance shifts aligned with affirmed gender. Overall functional metagenome analysis showed a statistically significant effect of gender and transition (R2 = 4.1%, P = 0.0115), emphasizing transitions aligned with affirmed gender, particularly in fatty acid-related metabolism.ConclusionsThis study provides compelling evidence of distinct taxonomic and functional profiles in the gut microbiota between trans men and women. GAHT induces androgenization in trans men and feminization in trans women, potentially impacting physiological and health-related outcomes.Trial registrationClinicaltrials.gov NCT02185274.

Abstract P189: Maternal Hyperandrogenemia Programs Hypoandrogenemia and Intrarenal Activation of Histone Deacetylase in Adult Male Offspring

Polycystic ovary syndrome ( PCOS ) is the most common endocrinopathy in young women. In-utero, children of ~80% of PCOS women in the US are exposed to maternal “hyperandrogenemia and obesity”. It remains unclear whether this exposure affects their cardiovascular ( CV ) health later in life. Using a well-characterized rat model of maternal PCOS, the hyperandrogenemic obese ( HAO ) dams, we previously showed that adult male, not female, offspring ( HAO F1 ) have enhanced blood pressure ( BP ) response to chronic angiotensin ( Ang ) II compared to sex-matched control offspring ( CON F1 ), suggesting their increased risk of later CV disease. Sex steroids have the potential to modulate epigenetics. Histone deacetylase ( HDAC ) and histone acetyltransferase ( HAT ) are markers of epigenetic modifications. HDACs have been shown to promote tumor necrosis factor ( TNF )-α expression and play a role in Ang II-induced hypertension. The present study was designed to test the hypothesis that male HAO F1 have intra-renal activation of HDAC and increased TNF-α that could play a role in their Ang II BP response. Methods: At 4 weeks ( wks ) of age, female SD rats were implanted (s.c.) with either 5α-dihydrotestosterone pellets (7.5 mg/90 d; HAO) or placebo pellets (CON) and mated at 9-12 wks. Offspring were obtained and weaned at 3 wks. Serum testosterone ( T; by LC/MS-MS), renal cortical TNF-α (Bioplex) and renal cortical nuclear HDAC and HAT activities (colorimetric assays) were measured in male offspring (1/litter, 16-24 wks, n=5-9). Results: Male HAO F1 had significantly lower serum T, higher renal cortical HDAC activity and TNF-α (430.2±124 vs 120.6±14 ng/dl, 0.97±0.1 vs 4.51±0.96 OD/min/mg protein and 423.7±47 vs 579.8±47 pg/g tissue, in male CON F1 vs male HAO F1 , respectively, p&lt;0.05), and no change in their renal cortical HAT activity (vs male CON F1 ). Conclusion: Male offspring born to HAO dams develop hypoandrogenemia that is associated with intra-renal activation of HDAC that could be mediating their increased intra-renal inflammation (TNF-α expression) and mediating their exaggerated BP response to Ang II. Future studies will determine the causative relationship between hypoandrogenemia, HDAC activation and TNF-a and their role in the exaggerated pressor response to Ang II in those male offspring. Funding: AHA-24DIVSUP1273026 (JA), NIH-NIGMS P20GM121334 (JFR, NMS), R01HL135089 &amp; R01AG075963 (JFR), AHA-22CDA938320 and 2024 Dean Franklin Award (NMS).

Abstract P148: Loss of Ovarian Estrogen Downregulates Renal Steroidogenesis

Hypertension impacts half of US adults and importantly is more prevalent in men than premenopausal women. Sex hormones, particularly estrogen, have been implicated in this sex-difference. Recently we showed renal medullary estrogenic signaling via the G protein-coupled estrogen receptor 1 promotes sodium excretion in female, but not male, Sprague Dawley (SD) rats which implicates estrogen as a possible female-specific natriuretic factor. This led us to question whether the kidney could produce its own steroids, including estrogen, to respond to salt load changes locally. Evidence in cultured COS-7 and fetal kidney cells indicates the expression and activity of steroidogenic enzymes. Recently, we showed the outer medulla of the female SD rat kidney expresses key enzymes and metabolites involved in sex steroid biosynthesis. It is unknown how ovarian estrogen regulates steroidogenesis in the kidney. We hypothesize that ovarian estrogen stimulates the intrarenal capacity to biosynthesize sex steroids. To test this, we measured mRNA expression of several steroidogenic enzymes in the renal outer medulla of gonadally-intact female or ovariectomized SD rats (N=6). Cholesterol is the initial substrate for steroid synthesis. Thus, we first measured HMG-CoA reductase (HMGCR), the key synthesizing enzyme for cholesterol and steroidogenic acute regulatory protein (StAR), which helps commit cholesterol to steroid synthesis. Ovariectomy (OVX) reduced mRNA expression of both when compared to intact females (HMGCR: 63.5 ± 6.2 vs 100.0 ± 10.7 P=0.0169; StAR: 66.6 ± 12.4 vs 100.0 ± 6.4 P=0.0298). Although not significantly different, OVX seemed to reduce the expression of hydroxysteroid 3-β Dehydrogenase, which converts several intermediate steps in androgen and estrogen synthesis, compared to intact females (73.4 ± 13.3 vs 100.0 ± 9.7 P=0.1283). Hydroxysteroid 17-β Dehydrogenase (17β-HSD) 1, which converts estrone to estradiol, was unchanged in OVX compared to intact females (107.6 ± 13.2 vs 100.0 ± 10.1 P=0.6537). OVX reduced expression of 17β-HSD2 (28.34 ± 7.8 vs 100.0 ± 12.85 P=0.0008) and 17β-HSD3 (71.1 ± 7.5 vs 100.0 ± 5.7 P=0.0097) which interconvert androstenedione and testosterone compared to intact females. Combined these data suggest that ovariectomy blunts the intrarenal machinery for steroidogenesis. Additional experiments are required to test whether menopause downregulates renal sex steroid biosynthesis and predisposes postmenopausal women to hypertension.

Abstract P142: Cross Sex Steroid Therapy and Cardiac Function in a Rodent Model of Gender Affirming Hormone Therapy in the Male Rat.

Transgender females ( TGF ) are individuals born biologically male, but identify as female. Gender-Affirming Hormone Therapy ( GAHT ) consists of 17β-Estradiol ( E2 ) supplementation with androgen suppression or a surgical intervention in order to match physical characteristics with perceived gender. Whether the prevalence of cardiovascular ( CV ) disease is enhanced in TGFs on GAHT is not clear. We previously reported that baseline cardiac morphology and function is not altered in a rat model of cross sex hormone therapy ( CSHT ) that mimics GAHT in the TGF. This study tested the hypothesis that myocardial ischemia will result in enhanced cardiac susceptibility in the male rat on CSHT. Adult male Sprague Dawley rats (13 weeks of age) were randomly assigned to either Control or E2+CTX ; E2 at 5 mg/day, pellet sc, replaced every 3 weeks with castration ( CTX ) performed at 15 weeks of age. At 25 weeks of age, rats in each group were randomly subdivided into Sham (n=8) or myocardial ischemia/reperfusion ( MIR ) , 1 hour occlusion, n=6-7. Statistics: Two-way ANOVA with Tukey’s post-hoc test. *Denotes significance vs. Control Sham. Results ( Table ): At 27 weeks of age, total lean mass (EchoMRI) was significantly decreased in Sham and I/R E2+CTX (p&lt;0.05). At one week post I/R, stroke volume and cardiac output (echocardiogram, VEVO 3100) were significantly decreased in E2+CTX Sham vs. Control Sham (p&lt;0.05); yet, ejection fraction, end-diastolic volume, and end-systolic volume did not differ. Thus, these data suggest that the biological effects of CSHT in the male does not enhance susceptibility to cardiac ischemia in young adulthood; yet, the long-term effect of CSHT on CV health remains unknown.

Autotaxin Expression in the Uterus of Cycling Rats.

Autotaxin (ATX), also known as ectonucleotide pyrophosphatase/phosphodiesterase family member 2 (ENPP 2), is an enzyme with lysophospholipase D activity that converts lysophosphatidylcholine into lysophosphatidic acid (LPA). One of the LPA receptors, LPA3, is positively and negatively regulated by progesterone and estrogen, respectively. Furthermore, ATX expression in the rat uterus could be under the control of estrous cycle. In the present study, we used young normal cycling rats for further assess the uterine ATX expression and localization by reverse transcription PCR (RT-PCR) and immunohistochemistry, respectively. In the RT-PCR study, ATX mRNA level at Metestrus (1.00±0.026 AU) was significantly higher than that at Proestrus (0.42±0.046 AU, p<0.001) and the level at Diestrus (0.75±0.107 AU, p<0.05) was significantly higher than that at Proestrus. Among the luminal epithelial cells, the order of the ATX signal intensities was Metestrus>Diestrus>Proestrus>Estrus. Among the myometrial cells, the order of the signal intensities was Diestrus>Proestrus>Estrus>Metestrus. Among the glandular epithelial cells, the order of the signal intensities was Proestrus>Estrus=Metestrus= Estrus. The present study indicates that expression and localization of uterine ATX may be under the control of sex steroids during the estrous cycle. Further studies on the ATX signaling-sex steroid relationship will be providing better understanding on in normal and pathophysiological state of uterus.

Reduced voluntary wheel running behaviour in Kiss1r knockout mice

Kisspeptin and its receptor, Kiss1r, are novel players in the central balance of energy intake and expenditure. Recent evidence also indicates that kisspeptin signalling is important in thermoregulation and generation of the circadian rhythm. We used global Kiss1r knockout mice (Kiss1r KO), which are hypogonadal and develop obesity, to determine the impact of kisspeptin on circadian related behaviour. Voluntary wheel running was examined in Kiss1r KO and wild-type (WT) mice, using gonad intact and gonadectomised (GDX) mice to account for the effects of kisspeptin on gonadal sex steroids. Intact male and female Kiss1r KO mice covered only 10% and 30% of the distance travelled each day by their respective WT controls. In all mice, most of the running activity occurred during the dark phase. GDX WT mice ran significantly less during dark periods than the intact WT. GDX Kiss1r KO male mice ran significantly less than the GDX WT male mice, but the decrease was attenuated compared to intact mice. There was no difference between the female GDX Kiss1r KO and GDX WT. In contrast to the obese phenotype that develops in Kiss1r KO mice, body mass at the end of the study was significantly lower in the GDX Kiss1r KO than it was in the GDX WT mice. The difference in wheel running activity was not associated with any histological change in WAT, BAT, or muscle diameter. No difference in immunohistochemistry expression was seen in lateral hypothalamic orexin neurons or dopamine neurons in the ventral tegmental area / substantia nigra. We observed increased Iba1 expression (activation of microglia) in the arcuate nucleus of male Kiss1r KO mice. Overall, the circadian locomotor activity in male Kiss1r KO mice appears dependent on kisspeptin signalling and the obese phenotype does not develop in Kiss1r KO mice when they engage in voluntary activity.

Diverse modulatory effects of sex steroids on depressive-like behavior in socially stressed female rats.

Diverse modulatory effects of sex steroids on depressive-like behavior in socially stressed female rats.

Effects of inulin on intestinal flora and metabolism-related indicators in obese polycystic ovary syndrome patients

ContextPolycystic ovary syndrome (PCOS), a common endocrine disorder in women of reproductive age, is closely associated with chronic low-grade inflammation and metabolic disturbances. In PCOS mice, dietary inulin has been demonstrated to regulate intestinal flora and inflammation. However, the efficacy of dietary inulin in clinical PCOS remains unclear.ObjectiveThe intestinal flora and related metabolic indexes of obese patients with polycystic ovary syndrome (PCOS) after 3 months of inulin treatment were analyzed.Setting and designTo analyze the intestinal flora and related metabolic indexes in healthy controls and obese patients with polycystic ovary syndrome after 3 months of inulin treatment.ResultsThe results showed that dietary inulin improved sex hormone disorders, reduced BMI and WHR levels in obese women with PCOS. In addition, the inulin intervention reduced plasma TNF-α, IL-1β, IL-6, and MCP-1levels. Inulin intervention increased the abundance of Actinobacteria, Fusobacteria, Lachnospira, and Bifidobacterium, as well as decreased the ratio of F/B and the abundance of proteobacteria, Sutterella, and Enterobacter. Correlation analyses showed a strong relationship among plasma inflammatory factors, sex steroid hormones, and the intestinal flora of patients.ConclusionsDietary inulin may improve obese PCOS women disease through the gut flora–inflammation–steroid hormone pathway.The clinical trial registration number: ChiCTR-IOR-17012281.

Improving Beef Cattle Production: Safety and Effectiveness of New Immunocastration Vaccine.

Reproductive control in mammals, particularly in beef production systems, is crucial for managing behaviors driven by sex steroids, which can cause biosecurity issues, reduced weight gain, and decreased meat quality. Additionally, controlling sexual activity in females prevents unwanted pregnancies when both sexes are housed together for fattening. Surgical castration in cattle, commonly performed under field conditions, is associated with significant welfare concerns due to pain and infection risks. Furthermore, castrating female cattle in the field is often impractically expensive. Hence, new reproductive control methods that prioritize animal welfare and are suitable for both sexes are essential. Immunocastration (IC), which involves vaccination against the GnRH-I hormone, has emerged as a promising alternative, demonstrating efficacy and safety in various species. Immunocastration has proven to be an effective alternative to surgical castration in controlling reproduction and promoting animal welfare in several species. This study aims to evaluate the safety, immunogenicity, immunocastration effect, and productive impact of a novel IC vaccine developed in Chile for female cattle. Two consecutive trials were conducted, the first under controlled conditions and the second under field conditions. The results demonstrated that the new vaccine is safe and effective for use in beef cattle, inducing specific immunity against GnRH-I, reducing gonadal functionality, and improving productive parameters. These findings suggest that this new IC vaccine can significantly benefit the beef cattle industry by providing a welfare-friendly and efficient method of reproductive control.

Per- and polyfluoroalkyl substances (PFAS) and hypertensive disorders of Pregnancy- integration of epidemiological and mechanistic evidence

BackgroundHypertensive disorders of pregnancy (HDP) remain a significant global health burden despite medical advancements. HDP prevalence appears to be rising, leading to increased maternal and fetal complications, mortality, and substantial healthcare costs. The etiology of HDP are complex and multifaceted, influenced by factors like nutrition, obesity, stress, metabolic disorders, and genetics. Emerging evidence suggests environmental pollutants, particularly Per- and polyfluoroalkyl substances (PFAS), may contribute to HDP development. ObjectiveThis review integrates epidemiological and mechanistic data to explore the intricate relationship between PFAS exposure and HDP. Epidemiological evidenceStudies show varying degrees of association between PFAS exposure and HDP, with some demonstrating positive correlations, particularly with preeclampsia. Meta-analyses suggest potential fetal sex-specific differences in these associations. Mechanistic insightsMechanistically, PFAS exposure appears to disrupt vascular hemodynamics, placental development, and critical processes like angiogenesis and sex steroid regulation. Experimental studies reveal alterations in the renin-angiotensin system, trophoblast invasion, oxidative stress, inflammation, and hormonal dysregulation – all of which contribute to HDP pathogenesis. Elucidating these mechanisms is crucial for developing preventive strategies. Therapeutic potentialTargeted interventions such as AT2R agonists, caspase inhibitors, and modulation of specific microRNAs show promise in mitigating adverse outcomes associated with PFAS exposure during pregnancy. Knowledge gaps and future directionsFurther research is needed to comprehensively understand the full spectrum of PFAS-induced placental alterations and their long-term implications for maternal and fetal health. This knowledge will be instrumental in developing effective preventive and therapeutic strategies for HDP in a changing environmental landscape.

A Review on Testosterone: Estradiol Ratio-Does It Matter, How Do You Measure It, and Can You Optimize It?

There is a natural balance between the major sex steroids, testosterone and estradiol, controlled by gonadal secretion and peripheral conversion by aromatase. This balance is impacted by a variety of inborn and acquired conditions, and, more recently, by a growing use of exogenous testosterone therapy and off-label aromatase use under the guise of "men's health." We summarize reported testosterone:estradiol ratios, both naturally occurring and with pharmacologic manipulation and consider the ramifications of significant changes in these ratios. However, significant limitations exist in terms of steroid separation and measurement techniques, timing of samples, and lack of consistency from one assay to another, as well as definition of normative data. Limited data on the testosterone:estradiol ratio in men exists, particularly due to the scan data on concurrent estradiol values in men receiving testosterone therapy or aromatase inhibitors. Nonetheless, there seems to be a range of apparently beneficial values of the testosterone: estradiol radio at between 10 and 30, calculated as: testosterone in ng/dL/estradiol in pg/mL. Higher values appear to be associated with improved spermatogenesis and reduced bone density while lower values are associated with thyroid dysfunction. While there is growing awareness of the significance of the testosterone:estradiol ratio, and a sense of a desired range, the optimal value has not yet been determined. Further work is needed to clarify the measurement strategies and clearly-defined outcome measures related to the testosterone:estradiol ratio.

Molluscicidal activity and biochemical impacts of borrelidins against an aquatic invasive snail Pomacea canaliculata for crop protection

The invasive golden apple snail Pomacea canaliculata is one of the devastating threats to aquatic ecosystems and wetland agriculture worldwide. Macrolides from microbes display various advantages over other compounds in controlling snails. However, emergence of antibiotic-resistant phenotypes against certain macrolides in the field appeals for exploring more effectively molluscicidal macrolides. Here, two borrelidins, borrelidin BN1 and BN2, from the extract of a Streptomyces strain fermentation were evaluated for molluscicidal potential against P. canaliculata using both immersion and contact bioassay methods. Borrelidin BN1 (borrelidin A) presented a significant molluscicidal activity comparable to the chemical pesticide metaldehyde, and had a much lower median lethal concentration value (LC50, 522.984 μg·ml−1) than avermectin B1 at 72 h of contact-killing treatment. Snail growth was inhibited by borrelidin BN1 more than by metaldehyde at sublethal concentrations, consistent with responses of key biochemical parameters. Exposure to borrelidin BN1 decreased the activity of acetylcholinesterase (AChE), glutathione S-transferase (GST), aspartate aminotransferase (AST), alanine aminotransferase (ALT) as well as the levels of energy reserves and sex steroids in snail tissues, while increased the activity of superoxide dismutase (SOD), catalase (CAT), lactate dehydrogenase (LDH) and the level of lipid peroxidation (LPO). Further application assay confirmed that borrelidin BN1 protected crop plant Zizania latifolia from P. canaliculata damage via suppressing snail population density. These findings suggest great potential of borrelidin BN1 as a molluscicide. Additionally, its higher activity than the stereoisomeric borrelidin BN2 (borrelidin F) implied better molluscicidal borrelidins could be acquired through structural optimization.

Influence of estrogen on right ventricular mitochondrial function in pulmonary hypertension

There is a female predominance in pulmonary arterial hypertension (PAH) with a ~4:1 female-to-male ratio. However, female PAH patients exhibit better right ventricular (RV) function and thus better survival than the males. The majority of the current PAH therapies target pulmonary vascular remodeling and/or vasoconstriction in the pulmonary vasculature. However, no therapies directly target the RV, partially because the underlying mechanisms of RV failure in PAH are not fully understood. Since the RV serves as the main determinant of mortality, clarifying the mechanism of RV failure and the associated sex differences in PAH may promote the development of novel therapeutic strategies. Numerous molecular abnormalities have been detected in RV in PAH, particularly due to the suppression of mitochondrial function, including the inhibition of glucose oxidation and a shift to uncoupled aerobic glycolysis (Warburg metabolism) and excessive mitochondrial fission. The mitochondrial suppression is associated with hypocontractility and increased apoptosis in RV cardiomyocytes, and the hyperproliferative, pro-fibrotic, and apoptosis-resistant phenotypes in RV fibroblasts in PAH. Mitochondria also serve as the site for sex steroid synthesis, and in turn, the sex steroids, particularly estradiol (E2), influence the mitochondria both indirectly and directly. It is not well understood how E2 affects mitochondrial function in RV in PAH. Hence, this review focuses on the key mitochondrial genes and proteins that are influenced by PAH, E2, and sex.

Molecular characterization and expression profiling of 3 beta-hydroxysteroid dehydrogenase and hydroxysteroid 17-beta dehydrogenase in response to HCG stimulation in striped murrel, Channa striata (Bloch, 1793)

Striped murrel (Channa striata) is highly valued in the Indian subcontinent and Southeast Asia for its nutritional and medicinal benefits. However, the limited availability of high-quality seeds of murrel and the asynchronous maturation of brooders, particularly during peak spawning seasons creates problems in aquaculture. Beta-hydroxysteroid dehydrogenases (β-HSDs) are steroidogenic enzymes involved in the biosynthesis of active steroids in gametogenesis and steroidogenesis. This study aimed to clone and characterize the full-length cDNA sequences of two crucial enzymes, 3-beta hydroxysteroid dehydrogenase (Hsd3β) and 17-beta hydroxysteroid dehydrogenase (Hsd17β). It resulted in full-length cDNA sequences for Hsd3β and Hsd17β with 1101bp and 771bp length, respectively, encoding 366 and 256 amino acids. Signal peptide analysis indicated that both proteins are secretory, and hydropathy profiles suggested their hydrophilic nature. Notably, Rossmann-fold NAD(P)(+)-binding domains characteristic of Short-chain dehydrogenases/reductases (SDR) family genes were identified in Hsd3β (between 9-355 aa) and in Hsd17β (between 10-254 aa). Gene expression analyses were performed in testes and ovaries using qPCR at three key stages: preparatory, mature, and 16 h post human chorionic gonadotropin (hCG) injection (16 hpi). Results demonstrated a significant 2-fold upregulation of Hsd17β in mature and 16 hpi testes, while Hsd3β showed a significant 10-fold upregulation in mature testes compared to premature and 16 hpi stages. Ovarian expression of Hsd3β and Hsd17β showed minimal expression upon hCG injection (P < 0.05). These findings contribute to our understanding of Beta-hydroxysteroid dehydrogenases (β-HSDs), providing insights into regulating sex steroid hormone synthesis during the gonadal development of striped murrel.