Genetic Sex Research Articles

Photosynthetic and antioxidant activity in the sex-related heat stress response of the dioecious species Rumex thyrsiflorus Fingerh.

Rumex thyrsiflorus Fingerh. is a dioecious species with heteromorphic sex chromosomes. Due to sexual dimorphism and the content of bioactive constituents used in pharmacology, this species is an interesting object of study. A complex analysis of selected physiological and biochemical aspects of the sex-related response to heat stress in vitro and in vivo was carried out. The experiment included in vitro regenerated plants and plants obtained from seeds. Regenerants were obtained from hypocotyls on Murashige and Skoog (MS) medium supplemented with 2.27 μM thidiazuron (TDZ). The sex of the plants was determined by molecular analysis based on genetic sex markers. Analysis of the main photosynthetic parameters indicated that in vitro regenerated plants showed a decrease in photosystem II (PSII) activity when directly exposed to a stressor. However, in contrast to the seed-derived plants, they adapted efficiently to the recovery conditions within 1 week after the stress was terminated. Furthermore, in vitro regenerated male and female plants acclimatised well to field conditions and showed greater stress tolerance based on better efficiency of the photosynthetic apparatus and the highest chlorophyll a/b ratio. In case of plants derived from seeds, male plants were less sensitive to heat stress and showed greater stability of PSII at high temperatures compared to female plants. The results showed that the response to high-temperature stress depends on the sex and the origin of the plants, i. e. in vitro regenerated plants versus plants obtained from seeds. Even short-term heat stress resulted in differences in photosynthetic efficiency. Biochemical analysis of antioxidant activity in response to heat stress, carried out for the first time in Rumex thyrsiflorus, has allowed the identification of the following forms of superoxide dismutase (SOD): manganese (MnSOD), iron (FeSOD) and two copper-zinc isoforms (Cu/ZnSOD I and Cu/ZnSOD II).

Management challenges of disorders of sex development- Case Series


 
 
 INTRODUCTION: Disorders of sex development (DSDs) are genetic abnormalities characterized by discordance between phenotypic, gonadal, and genetic sex. They are grouped into two categories based on karyotype: 46, XX DSD and 46, XY DSD.CASES: We reviewed two patients referred to the Rwanda Military Hospital genetic unit. The first patient was a 3-year-old toddler who was referred for confusing sex organs. Physical examination showed ambiguous genital organs with hypospadias and micropenis. Pelvic examination showed a swelling solid mass hat leading to a suspicion of ovary or undescended testes or combined ovary and testes (ovotestes). The second patient was a 17 years old teenager who presented with primary amenorrhea and lack of female secondary sexual characteristics at her age. The karyotype test was performed to investigate the genotypic sex of the patients and results revealed the karyotype formula of 46, XX/XY indicating the presence of two cell lines in the patient for the toddler and 46XYinv9 (p11q13) indicating the mismatch between the genotype and phenotype of the patients for the teenager.
 CONCLUSION: Patients were diagnosed with Disorder of Sex Development with 46, XX/XY and 46, XY genotypes respectively. A multidisciplinary team of a geneticist, urologist, endocrinologist and a psychologist reviewed the patient for the effective management.
 
 

Molecular Cloning and Expression Responses of Jarid2b to High-Temperature Treatment in Nile Tilapia (Oreochromis niloticus).

Nile tilapia is a GSD + TE (Genetic Sex Determination + Temperature Effect) fish, and high-temperature treatment during critical thermosensitive periods (TSP) can induce the sex reversal of Nile tilapia genetic females, and brain transcriptomes have revealed the upregulation of Jarid2 (Jumonji and AT-rich domain containing 2) expression after 36 °C high-temperature treatment for 12 days during TSP. It was shown that JARID2 forms a complex with polycomb repressive complex 2 (PRC2) that catalyzed H3K27me3, which was strongly associated with transcriptional repression. In this study, Jarid2b was cloned and characterized in Nile tilapia, which was highly conserved among the analyzed fish species. The expression of Jarid2b was upregulated in the gonad of 21 dpf XX genetic females after 12-day high-temperature treatment and reached a similar level to that of males. Similar responses to high-temperature treatment also appeared in the brain, heart, liver, muscle, eye, and skin tissues. Interestingly, Jarid2b expression was only in response to high-temperature treatment, and not to 17α-methyltestosterone (MT) or letrozole treatments; although, these treatments can also induce the sex reversal of genetic Nile tilapia females. Further studies revealed that Jarid2b responded rapidly at the 8th hour after high-temperature treatment. Considering that JARID2 can recruit PRC2 and establish H3K27me3, we speculated that it might be an upstream gene participating in the regulation of Nile tilapia GSD + TE through regulating the H3K27 methylation level at the locus of many sex differentiation-related genes.

Rising Hemoglobin A1c in the Nondiabetic Range Predicts Progression of Type 1 Diabetes As Well As Oral Glucose Tolerance Tests.

Biomarkers predicting risk of type 1 diabetes (stage 3) among children with islet autoantibodies are greatly needed to prevent diabetic ketoacidosis and facilitate prevention therapies. Children in the prospective The Environmental Determinants of Diabetes in the Young (TEDDY) study (n = 707) with confirmed diabetes-associated autoantibodies (GAD antibody, IA-2A, and/or insulin autoantibody) and two or more HbA1c measurements were followed to diabetes or median age 11.1 years. Once confirmed autoantibody positive, HbA1c was measured quarterly. Cox models and receiver operative characteristic curve analyses revealed the prognostic utility for risk of stage 3 on a relative HbA1c increase from the baseline visit or an oral glucose tolerance test (OGTT) 2-h plasma glucose (2-hPG). This HbA1c approach was then validated in the Type 1 Diabetes TrialNet Pathway to Prevention Study (TrialNet) (n = 1,190). A 10% relative HbA1c increase from baseline best marked the increased risk of stage 3 in TEDDY (74% sensitive; 88% specific). Significant predictors of risk for HbA1c change were age and HbA1c at the baseline test, genetic sex, maximum number of autoantibodies, and maximum rate of HbA1c increase by time of change. The multivariable model featuring a HbA1c ≥10% increase and these additional factors revealed increased risk of stage 3 in TEDDY (hazard ratio [HR] 12.74, 95% CI 8.7-18.6, P < 0.0001) and TrialNet (HR 5.09, 95% CI 3.3-7.9, P < 0.0001). Furthermore, the composite model using HbA1c ≥10% increase performed similarly to an OGTT 2-hPG composite model (TEDDY area under the curve [AUC] 0.88 and 0.85, respectively) and to the HbA1c model in TrialNet (AUC 0.82). An increase of ≥10% in HbA1c from baseline is as informative as OGTT 2-hPG in predicting risk of stage 3 in youth with genetic risk and diabetes-associated autoantibodies.

Identifying susceptibility factors for methylmercury-induced developmental neurotoxicity

Background and aim: Methylmercury (MeHg) exposures during pregnancy or childhood can cause developmental neurotoxicity (DNT), including cognitive, behavioral, and other effects. While many studies have reported on these effects, fewer have examined other factors that contribute to susceptibility to MeHg-induced DNT. The first objective of this project is to determine whether there are demographic, biological, psychosocial, societal, environmental, or other factors that may make developmentally exposed individuals more susceptible to these effects. A second objective is to develop a replicable approach for identifying susceptibility data in assessments of the health effects of chemicals. Methods: A systematic literature search for 2019-2021 aimed to identify all epidemiology studies that examined methylmercury exposure and DNT. Identified studies were then screened for susceptibility information at the title/abstract and full text levels by two reviewers. A search string was also developed and applied to title/abstracts to determine whether these studies could be identified without extensive screening. Susceptibility information was then summarized. Results: Data examining several potential susceptibility factors for MeHg were identified, including genetic polymorphisms, sex, maternal factors, nutritional status, and multi-chemical exposures. Conclusion: This project identifies potential susceptibility factors associated with MeHg and DNT. The methods applied to MeHg may be adapted and utilized for identifying and interpreting the literature on susceptibility factors for adverse health effects from other chemical exposures. Keywords: methylmercury, developmental neurotoxicity, susceptibility, systematic review, environmental justice Disclaimer: The views expressed in this abstract are those of the author and do not necessarily represent the views or the policies of the U.S. Environmental Protection Agency.

Identification of Male-Specific Molecular Marker and Development of PCR-Based Genetic Sex Identification Technique in Spotted Knifejaw (Oplegnathus punctatus).

Spotted knifejaw (Oplegnathus punctatus) is a marine teleost species that is economically important for aquaculture and marine pasture proliferation and shows obvious bisexual growth dimorphism, but molecular sex markers are currently lacking. A 290bp (base pair) insertion with two fragments (230bp and 60bp) was identified in male individuals of O. punctatus based on whole-genome sequencing scanning and structural variation analyses. The gene annotation results showed that the insertion event occurred in the Igfn1 gene of male O. punctatus. The results of amino acid analysis further showed that the insertion event resulted in the functional variation of Igfn1 in male O. punctatus, and recombination caused the inactivation of Igfn1. According to the male-specific insertion information, we designed a PCR-based genetic amplification technique for rapid sex identification in O. punctatus. The results of agarose gel electrophoresis showed that two DNA fragments of 635bp and 925bp were amplified in male O. punctatus, while only a single DNA fragment of 635bp was amplified in female individuals. The sex of individuals identified by this method was consistent with their known phenotypic sex, which will improve sex identification efficiency. This method provides a new DNA marker for rapid sex identification in O. punctatus, which has great significance and application value in monosex breeding and provides new insights for the study of Igfn1 gene recombination and inactivation in male O. punctatus.

Evaluating Morphological Methods for Sex Estimation on Isolated Human Skeletal Materials: Comparisons of Accuracies between German and South African Skeletal Collections

Objectives: The focus of this research is to evaluate the sex estimation methods on isolated human materials by applying morphological methods published in various forensic and anthropological literature on different skeletal series. Materials and Methods: 165 individuals from the 19th to 20th century Inden skeletal series, 252 individuals from the 13th to 14th century Lübeck skeletal series of German ancestry housed at the Department of Historical Anthropology and Human Ecology, the University of Göttingen, Germany, and 161 individuals from the 19th and 20th century of South African African ancestry housed within the Raymond A. Dart collection of modern human skeletons at the University of Witwatersrand, South Africa, with crania, mandibles, and pelves, were assessed. The evaluation criteria are burial information on the Inden series, genetic sex on both the Inden and the Lübeck series, and previous demography on cadavers from the South African African series. Results and Discussion: The sex estimation with cranial traits perform better in Inden and South Africa samples and worse in Lübeck sample. The mandible accuracies for pooled sexes are not exemplary, but the individual traits perform better for males in the Inden, Lübeck, and South Africa samples, except for gonion and angle, which performs better in females. The pelvic traits perform better in the Inden and South Africa samples compared to the Lübeck sample. The statistical tests show that there is a huge difference in the accuracy rates and the performance between both population groups from Germany itself, considering that Inden and Lübeck samples share the same ancestry. The accuracy rates improve with the exclusion of ambiguous individuals.

Whole-Genome Inter-Sex Variation in Russian Sturgeon (Acipenser gueldenstaedtii).

The Russian sturgeon (Acipenser gueldenstaedtii, AG) is an endangered fish species increasingly raised on fish farms for black caviar. Understanding the process of sex determination in AG is, therefore, of scientific and commercial importance. AG lacks sexual dimorphism until sexual maturation and has a predominantly octoploid genome without a definite sex chromosome. A conserved short female-specific genomic sequence was recently described, leading to the development of a genetic sex marker. However, no biological function has been reported for this sequence. Thus, the mechanism of sex determination and the overall inter-sex genomic variation in AG are still unknown. To comprehensively analyze the inter-sex genomic variation and assess the overall inter-species variation between AG and A. ruthenus (AR, sterlet), a related tetraploid sturgeon species, we performed whole-genome sequencing on DNA from 10 fish-farm-raised adult AG (5 males and 5 females). We produced a partially assembled, ~2390 MBp draft genome for AG. We validated in AG the female-specific region previously described in AR. We identified ~2.8 million loci (SNP/indels) varying between the species, but only ~7400 sex-associated loci in AG. We mapped the sex-associated AG loci to the AR genome and identified 15 peaks of sex-associated variation (10 kb segments with 30 or more sex-associated variants), 1 of which matched the previously reported sex-variable region. Finally, we identified 14 known and predicted genes in proximity to these peaks. Our analysis suggests that one or more of these genes may have functional roles in sex determination and/or sexual differentiation in sturgeons. Further functional studies are required to elucidate these roles.

Investigation of genetic sex of GIFT strain of tilapia in Bangladesh using Y‐linked Amh marker

Investigation of genetic sex of <scp>GIFT</scp> strain of tilapia in Bangladesh using Y‐linked <i>Amh</i> marker

Evolutionary Transitions Between Hermaphroditism and Dioecy in Animals and Plants

We review transitions between hermaphroditism and dioecy in animals and (mainly flowering) plants. Although hermaphroditism and dioecy represent two end states in a sex-allocation continuum, both vary in major ways among clades. However, drawing on sex-allocation theory and distinguishing between self-fertilization and outcrossing, we recognize five broad paths to dioecy and two broad paths to hermaphroditism. Which path is taken likely depends on the starting state (especially in terms of the mating system), as well as the ecological setting or genetic context of the transition. Androdioecy may have been more important in some transitions to dioecy than current theory would suggest, and gynodioecy may often be an evolutionary end point in itself rather than a step between hermaphroditism and dioecy. Transitions between environmental and genetic sex determination may also play an important role in sexual-system evolution. Further theory is required to address these possibilities. Detailed empirical work is also greatly needed, especially in animal clades that vary in their sexual system.

Host genetics and pathogen species modulate infection-induced changes in social aggregation behaviour.

Identifying how infection modifies host behaviours that determine social contact networks is important for understanding heterogeneity in infectious disease dynamics. Here, we investigate whether group social behaviour is modified during bacterial infection in fruit flies (Drosophila melanogaster) according to pathogen species, infectious dose, host genetic background and sex. In one experiment, we find that systemic infection with four different bacterial species results in a reduction in the mean pairwise distance within infected female flies, and that the extent of this change depends on pathogen species. However, susceptible flies did not show any evidence of avoidance in the presence of infected flies. In a separate experiment, we observed genetic- and sex-based variation in social aggregation within infected, same-sex groups, with infected female flies aggregating more closely than infected males. In general, our results confirm that bacterial infection induces changes in fruit fly behaviour across a range of pathogen species, but also highlight that these effects vary between fly genetic backgrounds and can be sex-specific. We discuss possible explanations for sex differences in social aggregation and their consequences for individual variation in pathogen transmission.

A Fish of Multiple Faces, Which Show Us Enigmatic and Incredible Phenomena in Nature: Biology and Cytogenetics of the Genus Carassius.

Sexual vs. asexual reproduction—unisexual vs. bisexual populations—diploid vs. polyploid biotypes—genetic vs. environmental sex determination: all these natural phenomena are associated with the genus of teleost fish, Carassius. This review places emphasis on two Carassius entities with completely different biological characteristics: one globally widespread and invasive Carassius gibelio, and the other C. carassius with a decreasing trend of natural occurrence. Comprehensive biological and cytogenetic knowledge of both entities, including the physical interactions between them, can help to balance the advantages of highly invasive and disadvantages of threatened species. For example, the benefits of a wide-ranged colonization can lead to the extinction of native species or be compensated by parasitic enemies and lead to equilibrium. This review emphasizes the comprehensive biology and cytogenetic knowledge and the importance of the Carassius genus as one of the most useful experimental vertebrate models for evolutionary biology and genetics. Secondly, the review points out that effective molecular cytogenetics should be used for the identification of various species, ploidy levels, and hybrids. The proposed investigation of these hallmark characteristics in Carassius may be applied in conservation efforts to sustain threatened populations in their native ranges. Furthermore, the review focuses on the consequences of the co-occurrence of native and non-native species and outlines future perspectives of Carassius research.

The Rattlesnake W Chromosome: A GC-Rich Retroelement Refugium with Retained Gene Function Across Ancient Evolutionary Strata.

Sex chromosomes diverge after the establishment of recombination suppression, resulting in differential sex-linkage of genes involved in genetic sex determination and dimorphic traits. This process produces systems of male or female heterogamety wherein the Y and W chromosomes are only present in one sex and are often highly degenerated. Sex-limited Y and W chromosomes contain valuable information about the evolutionary transition from autosomes to sex chromosomes, yet detailed characterizations of the structure, composition, and gene content of sex-limited chromosomes are lacking for many species. In this study, we characterize the female-specific W chromosome of the prairie rattlesnake (Crotalus viridis) and evaluate how recombination suppression and other processes have shaped sex chromosome evolution in ZW snakes. Our analyses indicate that the rattlesnake W chromosome is over 80% repetitive and that an abundance of GC-rich mdg4 elements has driven an overall high degree of GC-richness despite a lack of recombination. The W chromosome is also highly enriched for repeat sequences derived from endogenous retroviruses and likely acts as a “refugium” for these and other retroelements. We annotated 219 putatively functional W-linked genes across at least two evolutionary strata identified based on estimates of sequence divergence between Z and W gametologs. The youngest of these strata is relatively gene-rich, however gene expression across strata suggests retained gene function amidst a greater degree of degeneration following ancient recombination suppression. Functional annotation of W-linked genes indicates a specialization of the W chromosome for reproductive and developmental function since recombination suppression from the Z chromosome.

Omics approaches to discover pathophysiological pathways contributing to human pain.

Omics approaches to discover pathophysiological pathways contributing to human pain.

Karyotypic Analysis of Children with Disorders of Sex Development (DSD) at Children Hospital &amp; ICH, Lahore

Aim: To determine the frequency of different karyotypes in children with DSD presented at The Children Hospital &amp; ICH, Lahore Study design: Cross sectional analytical Place and Duration of Study: Department of Genetics, Children Hospital and ICH, Lahore, from Jan 2016 to June 2017. Methodology: The study was conducted on 83 adolescent children with any form of DSD after taking an informed consent. A detailed history was taken and sex of rearing was noted. Physical examination was done to know the morphological sex while karyotyping of all the cases was done for the confirmation of their genetic sex. All the findings were recorded on a predesigned proforma. The cases that have undergone any surgical correction procedure for genital ambiguity were excluded. Data was analyzed by SPSS 21. Results: Out of 83 cases, 27(32.5%) cases were reared as male at birth while 56(67.4%) were reared as female. Karyotypic analysis was done in all 83 cases. 27 cases who were reared as male, their karyotypic analysis of male sex of rearing showed a chromosomal compliment of 46XY in 25(92.5%), 46XX in 01(3.7%), 46XXY in 01(3.7%). Out of 56 cases of female sex of rearing, 45(80.3%) had 46XX karyotype 03(5.3%) had 46XY karyotype, 45X0 in 07(12.5%) and one case (1.7%) showed a XXX karyotype. Conclusion: To ensure the high-quality life for such an individual, there is an urgent need for correct sex assignment. Chromosomal analysis is important as a first step in determining an accurate genetic sex before the costly diagnostic tests and surgical procedure. Keywords: Intersex, Ambiguous genitalia, Karyotyping

Corazonin Neurons Contribute to Dimorphic Ethanol Sedation Sensitivity in Drosophila melanogaster.

Exposure to alcohol has multiple effects on nervous system function, and organisms have evolved mechanisms to optimally respond to the presence of ethanol. Sex differences in ethanol-induced behaviors have been observed in several organisms, ranging from humans to invertebrates. However, the molecular mechanisms underlying the dimorphic regulation of ethanol-induced behaviors remain incompletely understood. Here, we observed sex differences in ethanol sedation sensitivity in Drosophila Genome Reference Panel (DGRP) lines of Drosophila melanogaster compared to the absence of dimorphism in standard laboratory wildtype and control lines. However, in dose response experiments, we were able to unmask dimorphic responses for the control mutant line w1118 by lowering the testing ethanol concentration. Notably, feminization of the small population of Corazonin (Crz) neurons in males was sufficient to induce female-like sedation sensitivity. We also tested the role of the transcription factor apontic (apt) based on its known expression in Crz neurons and its regulation of sedation responses. Interestingly, loss of function apt mutations increased sedation times in both males and females as compared to controls. No significant difference between male and female apt mutants was observed, suggesting a possible role of apt in the regulation of dimorphic ethanol-induced responses. Thus, our results shed light into the mechanisms regulating sex-differences in ethanol-induced behaviors at the cellular and molecular level, suggesting that the genetic sex in a small neuronal population plays an important role in modulating sex differences in behavioral responses to ethanol.

Sex-specific association between coffee consumption and incident chronic kidney disease: a population-based analysis of 359,906 participants from the UK Biobank.

Background:The risk for chronic kidney disease (CKD) is influenced by genetic predisposition, sex, and lifestyle. Previous research indicates that coffee is a potentially protective factor in CKD. The current study aims to investigate whether sex disparity exists in the coffee–CKD association, and whether genetic risk of CKD or genetic polymorphisms of caffeine metabolism affect this association.Methods:A total of 359,906 participants from the UK Biobank who were enrolled between 2006 and 2010 were included in this prospective cohort study, which aimed to estimate the hazard ratios for coffee intake and incident CKD using a Cox proportional hazard model. Allele scores of CKD and caffeine metabolism were additionally adjusted for in a subsample with qualified genetic data (n = 255,343). Analyses stratified by genetic predisposition, comorbidities, and sex hormones were performed. Tests based on Bayesian model averaging were conducted to ascertain the robustness of the results.Results:Coffee was inversely associated with CKD in a dose-dependent manner. The effects of coffee did not differ across different strata of genetic risk for CKD, but were more evident among slower genetically predicted caffeine metabolizers. Significant sex disparity was observed (P value for interaction = 0.013), in that coffee drinking was only associated with the risk reduction of CKD in females. Subgroup analysis revealed that testosterone and sex hormone-binding globulin (SHBG), but not estradiol, modified the coffee–CKD association.Conclusions:In addition to the overall inverse coffee–CKD association that was observed in the general population, we could also establish that a sex disparity existed, in that females were more likely to experience the benefit of the association. Testosterone and SHBG may partly account for the sex disparity.

Abstract 1532: Short RNAs v2.0: isomiRs, tRFs, and rRFs represent numerous novel opportunities for developing potent, precision-medicine-aware diagnostics, prognostics, and therapeutics

Abstract Background: It has been twenty-eight years since the first microRNA (miRNA) was reported in the worm C. elegans. Since then, researchers have discovered miRNAs in animals, plants, and viruses. They also showed that miRNAs are critical regulators of many cellular processes in homeostasis and disease. The advent of deep sequencing helped discover many novel miRNAs, pinpointed miRNAs that are dysregulated in cancers and other diseases, and established that miRNAs have isoforms (isomiRs). Deep sequencing also proved instrumental in discovering two more populous classes of short RNAs, the tRNA-derived fragments (tRFs) and the rRNA-derived fragments (rRFs). In the last decade, others and we generated strong evidence that isomiRs, tRFs, and rRFs regulate messenger RNA (mRNA) and protein abundance, directly and indirectly. Methods: IsomiRs, tRFs, and rRFs arise from precursors whose genomic distribution is non-random. Many of these precursors contain sequence segments that resemble one another's or are present in unrelated genomic sequences. These factors obfuscate the molecules’ identity and genomic origin, muddle their biogenesis details, and complicate the design of experiments. Thus, to help study isomiRs, tRFs, and rRFs we had to develop specialized tools that tackle these complications. We analyzed tens of thousands of human samples using these tools, including specimens of primary human tissues, cancer cell lines, and biofluids. Results: We were the first to show that the expression of isomiRs, tRFs, and rRFs is regimented and depends on tissue type and disease. We were also first to show that their expression additionally depends on genetic ancestry, sex, and age. Our findings highlight the involvement of isomiRs, tRFs, and rRFs in previously unsuspected regulatory interactions. These interactions are currently uncharacterized and depend on cell context and, unexpectedly, on personal attributes. These dependencies are consequential. Indeed, we showed for many cancers that specific isomiRs, tRFs, and rRFs predispose patients of a given sex or ancestry to aggressive cancer biology. Conclusions: Our pan-cancer analyses show that isomiRs, tRFs, and rRFs offer unparalleled granularity when studying normal physiology, cancer, and the molecular biology of health disparities. Improving our understanding of the molecules’ dependence on tissue, disease, and personal attributes (e.g., sex, ancestry, age) will help develop better diagnostics, prognostics, and new approaches to personalized therapies. Preliminary reports provide strong evidence in this regard. Because very little is known currently about these three classes of short RNAs, data-driven approaches will be essential to all these efforts. Citation Format: Isidore Rigoutsos. Short RNAs v2.0: isomiRs, tRFs, and rRFs represent numerous novel opportunities for developing potent, precision-medicine-aware diagnostics, prognostics, and therapeutics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1532.

Biotechnological manipulation of the transition from genetic to temperature-dependent sex determination to obtain high quality neomale in aquaculture

Sex control is an essential technology to produce mono-sex populations with high growth rates and product quality in aquaculture. To produce an all-female population in fish with the XX/XY sex determination system, the generation of XX neomales is the critical step and they have been successfully created by different approaches, such as androgens, aromatase inhibitors and high temperature treatment. However, there is no comprehensive comparison of testis structure, quality of sperm and offspring in XX neomales produced by different approaches. Yellow catfish are an excellent model to study sex determination and sex reversal since robust sex-specific molecular markers and genetic sex determination have been identified. Previously, we observed that 17α-methyltestosterone (MT) treatment could not induce functional testes in XX yellow catfish. In this study, we found that high-temperature treatment caused a delay in ovarian development instead of sex reversal in yellow catfish. However, high temperature combined with aromatase inhibitor (Letrozole, LZ) treatment could dramatically improve the efficiency of sex reversal compared with using LZ alone (the neomale was designated XXm-LZ), while they showed the same testis phenotype. Interestingly, the offspring of XXm-LZ transitioned from genetic to temperature-dependent sex determination, which could be easily sex reversed after treatment with high temperature (the neomale was designated XXm-HT-1). Then, we evaluated the reproductive performances and sperm parameters in XY male, XXm-LZ and XXm-HT-1 neomales. Strikingly, the fertilization rate, hatching rate and survival rate of XXm-HT-1 catfish were as good as those of XYm yellow catfish and better than those of XXm-LZ yellow catfish, while the malformation rate of fries produced by XXm-HT-1 catfish was significantly lower than that of XXm-LZ catfish. In addition, the expression of miR-141/−200a/−429b and dmrt1/pfpdz1 was negatively and positively correlated with sperm quality, respectively. However, the transition from genetic to temperature-dependent sex determination was transient and cannot be completely inherited by the next generation in yellow catfish. We concluded that precise application of the transition from genetic to temperature-dependent sex determination could produce the highest quality neomales for sex control in aquaculture after comparing different approaches.

Sex Differences in Acute Neuroendocrine Responses to Stressors in Rodents and Humans.

Sex differences in the neuroendocrine response to acute stress occur in both animals and humans. In rodents, stressors such as restraint and novelty induce a greater activation of the hypothalamic-pituitary-adrenal axis (HPA) in females compared to males. The nature of this difference arises from steroid actions during development (organizational effects) and adulthood (activational effects). Androgens decrease HPA stress responsivity to acute stress, while estradiol increases it. Androgenic down-regulation of HPA responsiveness is mediated by the binding of testosterone (T) and dihydrotestosterone (DHT) to the androgen receptor, as well as the binding of the DHT metabolite, 3β-diol, to the β form of the estrogen receptor (ERβ). Estradiol binding to the α form of the estrogen receptor (ERα) increases HPA responsivity. Studies of human sex differences are relatively few and generally employ a psychosocial paradigm to measure stress-related HPA activation. Men consistently show greater HPA reactivity than women when being evaluated for achievement. Some studies have found greater reactivity in women when being evaluated for social performance. The pattern is inconsistent with rodent studies but may involve the differential nature of the stressors employed. Psychosocial stress is nonphysical and invokes a significant degree of top-down processing that is not easily comparable to the types of stressors employed in rodents. Gender identity may also be a factor based on recent work showing that it influences the neural processing of positive and negative emotional stimuli independent of genetic sex. Comparing different types of stressors and how they interact with gender identity and genetic sex will provide a better understanding of sex steroid influences on stress-related HPA reactivity.