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Sex steroids influence early organization of neural structures involved in expression of sexual behavior. A critical perinatal period during which testosterone surges occur has been identified in male rodents. Data are lacking for females, whose ovarian activity starts later in the postnatal period. Minipuberty has been described in female as a first postnatal period of gonadotropic axis activation. We transiently disrupted the minipubertal period, using daily injections of GnRH antagonist or aromatase inhibitor. The results showed unchanged puberty initiation and mild disturbance of estrus cyclicity. Minor modifications of some components of sexual behavior (olfactory preference, ability to attract male) were observed, but had no impact on lordosis behavior. Interestingly, letrozole-treated female mice showed increased anxiety state level at adulthood. This period therefore does not seem to be a key organizational window for female sexual behavior but appears to participate in the organization of neural structures involved in anxiety-related behavior. [ABSTRACT FROM AUTHOR]

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Grass carp belongs to Cypriniformes, Cyprinidae, and Cyprinus family, and is typically referred to as the four famous domestic fishes, black carp, silver carp, and bighead carp, respectively. The annual production of Chinese grass carp is consistently among the highest, with an output of 5.905 million tons in 2022, accounting for 24.3% of total of freshwater fish production. Reproduction is the core process of fish reproduction. Normal gonad development is a prerequisite for fish reproduction. At present, there are few reports on the sex differentiation of Chinese grass carp. Studying the differentiation and development of grass carp gonads can provide a typical model for gonadal development of cyprinid fish. In contrast, the start and completion time of gonadal differentiation are one of the key factors inducing sex reversal in fish using hormones. Research on gonadal differentiation and development in grass carp can also lay the foundation for the establishment of a unisexual population of grass carp.Sex-related genes play important roles in biological processes such as sex determination, gonadal differentiation, and reproduction and development in fish. In most differentiated teleost fish, genes such as dmrt1, sox9, foxl2, amh, and cyp19a1a, are considered the key genes involved in sex regulation. cyp19a1a plays a key role in the gonadal differentiation and ovarian development of teleost fish by aromatizing androgens into estrogen via aromatase activity. This gene is specifically expressed in the gonads and is used served as a characteristic gene for sex differentiation towards females. Anti-Müllerian hormone (amh) regulates the structure of reproductive organs and the differentiation and development of reproductive cells. In fish such as carp, rainbow trout, and grass carp, the expression level of the amh gene in the testes is significantly higher than that in the ovaries, and is often used as a characteristic gene for male differentiation.To explore the sex differentiation and developmental patterns of grass carp gonads, this study analyzed the tissue structure and expression differences of sex characteristic genes cyp19a1a and amh in the gonads of grass carp at 1, 2, 3, 4, 5, 6, 12, 24, 36, and 48 months of age using tissue sectioning technology and real-time fluorescence quantification technology. The results of tissue sectioning showed that grass carp exhibited reproductive ridges at 1-month-old. At 2 months of age, primitive germ cells were first observed in the reproductive crest, marking the formation of their primitive gonads. At 3-month- old, ovarian cavities and lobules were observed in the gonads of female grass carp. At 4-month-old, oogonia was observed, indicating anatomical differentiation at 3-month-old and cytological differentiation at 4-month-old. At the age of 4 and 5 months, ductus deferens and spermatogonia were respectively observed in male grass carp gonads, indicating anatomical differentiation at 4 months and cytological differentiation at 5 months. The ovaries of 24, 36, and 48-month-old grass carp were in the first, second, third, and fourth stages of development, respectively, while the testes were in the second, second, third, and fourth stages of development, respectively. At 48 months of age, the gonads of grass carp have matured. The fluorescence quantitative results showed that the expression level of the female characteristic gene cyp19a1a in the ovary showed an overall trend of first increasing, then decreasing, and then increasing again. The expression level of this gene was significantly upregulated at 2 months of age (P < 0.05), and reached its peak at 3, 6, and 48 months of age. During these three periods, anatomical changes were observed in the female gonads in the tissue sections, with a large proliferation of oocytes and the gonads tending to mature. The expression level of the male characteristic gene amh in the testes showed an overall trend of first increasing and then decreasing. At 2 months of age, the expression level of this gene was significantly upregulated (P < 0.05). At 5 months of age, it reached the peak when there were a large proliferation of spermatogonia in the gonads, and then remained low expression until gonadal maturity.In summary, this study confirmed that the initiation time of grass carp gonadal development is approximately 2 months old, and the differentiation time of male and female gonads is approximately 3 and 4 months old, respectively. By the age of 6 months, both male and female grass carp gonads completely differentiated. These results not only enrich the reproductive physiology data of grass carp but also provide a reference basis for the study of hormone-induced sex reversal technology in grass carp.

Introduction: Mammalian reproductive and somatic development is regulated by steroid hormones, growth hormone (GH), and insulin-like growth factor-1 (IGF-1). Based largely on information from humans, model organisms, and domesticated animals, testosterone (T) and the GH/IGF-1 system activate sexually differentiated development, promoting male-biased growth, often at a cost to health and survivorship. To test if augmented prenatal androgen exposure in females produces similar developmental patterns and trade-offs, we examine maternal effects in wild meerkats (Suricata suricatta), a non-model species in which adult females naturally, albeit differentially by status, express exceptionally high androgen concentrations, particularly during pregnancy. In this cooperative breeder, the early growth of daughters predicts future breeding status and reproductive success. Methods: We examine effects of normative and experimentally induced variation in maternal androgens on the ontogenetic patterns in offspring reproductive hormones (androstenedione, A4; T; estradiol, E2), IGF-1, growth from pup emergence at 1 month to puberty at 1 year, and survivorship. Specifically, we compare the male and female offspring of dominant control (DC or high-T), subordinate control (SC or lower-T), and dominant treated (DT or blocked-T) dams, the latter having experienced antiandrogen treatment in late gestation. Results: Meerkat offspring showed sex differences in absolute T and IGF-1 concentrations, developmental rates of A4 and E2 expression, and survivorship -- effects that were sometimes socially or environmentally modulated. Atypical for mammals were the early male bias in T that disappeared by puberty, the absence of sex differences in A4 and E2, and the female bias in IGF-1. Food availability was linked to steroid concentrations in females and to IGF-1, potentially growth, and survival in both sexes. Maternal treatment significantly affected rates of T, E2, and IGF-1 expression, and weight, with marginal effects on survivorship; offspring of DT dams showed peak IGF-1 concentrations and the best survivorship. Discussion: Maternal effects thus impact offspring development in meerkats, with associated trade-offs: Whereas prenatal androgens modify postnatal reproductive and somatic physiology, benefits associated with enhanced competitiveness in DC lineages may have initial costs of reduced IGF-1, delay in weight gain, and decreased survivorship. These novel data further confirm the different evolutionary and mechanistic pathways to cooperative breeding and call for greater consideration of natural endocrine variation in both sexes. [ABSTRACT FROM AUTHOR]

To bring about sexual dimorphism in form, information from the sex determination pathway must trigger sex-specific modifications in developmental programs. DM-domain encoding genes have been found to be involved in sex determination in a multitude of animals, often at the level of male somatic gonad formation. Here we report our findings that the DM-domain transcription factors MAB-3 and DMD-3 function together in multiple steps during the late stages of C. elegans male somatic gonad development. Both mab-3 and dmd-3 are expressed in the linker cell and hindgut of L4 males and dmd-3 is also expressed in presumptive vas deferens cells. Furthermore, dmd-3 , but not mab-3 , expression in the linker cell is downstream of nhr-67, a nuclear hormone receptor that was previously shown to control late stages of linker cell migration. In mab-3 ; dmd-3 double mutant males, the last stage of linker cell migration is partially defective, resulting in aberrant linker cell shapes and often a failure of the linker cell to complete its migration to the hindgut. When mab-3; dmd-3 double mutant linker cells do complete their migration, they fail to be engulfed by the hindgut, indicating that dmd-3 and mab-3 activity are essential for this process. Furthermore, linker cell death and clearance are delayed in mab-3; dmd-3 double mutants, resulting in the linker cell persisting into adulthood. Finally, DMD-3 and MAB-3 function to activate expression of the bZIP transcription factor encoding gene zip-5 and downregulate the expression of the zinc metalloprotease ZMP-1 in the linker cell. Taken together, these results demonstrate a requirement for DM-domain transcription factors in controlling C. elegans male gonad formation, supporting the notion that the earliest DM-domain genes were involved in male somatic gonad development in the last common ancestor of the bilaterians. [Display omitted] • Two C. elegans DM domain transcription factor encoding genes, mab-3 and dmd-3 , are expressed in multiple tissues involved in male somatic gonad development. • m ab-3; dmd-3 double mutants display defects in linker cell migration, resulting in aberrant linker cell morphology and premature arrest in many double mutant males. • m ab-3; dmd-3 double mutants also display defects in linker cell engulfment by the hindgut and subsequent linker cell death and clearance. • MAB-3 and DMD-3 partially inhibit expression of the zinc matrix metalloproteinase encoding gene zmp-1 and activate expression of a basic leucine zipper containing transcription factor encoding gene zip-5 in the linker cell. • These results support the hypothesis that ancestral DM-domain genes were involved in male somatic gonad development. [ABSTRACT FROM AUTHOR]

X chromosome centromeric drive may explain the prevalence of polycystic ovary syndrome and contribute to oocyte aneuploidy, menopause, and other conditions. The mammalian X chromosome may be vulnerable to meiotic drive because of X inactivation in the female germline. The human X pericentromeric region contains genes potentially involved in meiotic mechanisms, including multiple SPIN1 and ZXDC paralogs. This is consistent with a multigenic drive system comprising differential modification of the active and inactive X chromosome centromeres in female primordial germ cells and preferential segregation of the previously inactivated X chromosome centromere to the polar body at meiosis I. The drive mechanism may explain differences in X chromosome regulation in the female germlines of the human and mouse and, based on the functions encoded by the genes in the region, the transmission of X pericentromeric genetic or epigenetic variants to progeny could contribute to preeclampsia, autism, and differences in sexual differentiation. [ABSTRACT FROM AUTHOR]

The sex differentiation of Chinese alligator displays temperature-dependent sex determination, which occurs in the temperature-sensitive period (TSP) of embryonic development. Despite studies identifying genes involved in sex determination in the Chinese alligator, the complex mechanisms underlying their role remain a scientific mystery awaiting further exploration. In this study, before and after sex differentiation, six sampling points, FPT (F1-F6) and MPT (M1-M6), were established to explore TSP, candidate genes for sex differentiation, and lentivirus validation. We discovered that F4-vs-F5 and M4-vs-M5 exhibited the highest number of differential genes, with distinctive morphological characteristics of oocytes and spermatotubules during the F5 and M5 stages, respectively. Consequently, we speculate that the TSPs are F4 and M4. Through RNA-seq analysis, we identified genes potentially, such as MAEL, influencing sex differentiation and constructed lentivirus to explore its mechanism. LV-MAEL-shRNA and LV-MAEL-OE successfully invaded the gonads of Chinese alligator in vitro and in vivo experiments. knockdown of MAEL can reduce the male sex determining gene Dmrt1 by about 70 %. These findings suggest that MAEL, acting as a transcription factor, may play a role in sex determination by regulating Dmrt1. This study advances understanding of sex determination in Chinese alligator, establishing a foundation for future research.

Objectives: This study aimed at integrating the clinical and phenotypic characteristics, hormonal profile and genetic diagnosis of children with malformation syndromes associated with XY disorders of sex development (DSD) in a single-center in Egypt. Methods: This retrospective study included patients with syndromic XY DSD recruited from the Pediatric Endocrinology and Surgery units at Alexandria University Children's Hospital (AUCH), Alexandria, Egypt, between 2018 and 2023. All patients included in the study underwent a detailed clinical and laboratory evaluation, ultrasonography (and laparoscopy if needed). Results: The study included 30 children with syndromic XY DSD; most of these children were diagnosed at birth. The most common extragenital malformations included skeletal anomalies (70%), facial dysmorphism (46.7%), cerebral malformations (30%) and congenital heart disease (23.3%). Ventricular septal defect was the most common congenital heart disease. Conclusion: Integration between clinical, laboratory and genetic data is the cornerstone in the management of XY DSD patients for appropriate decision making of surgical intervention and sex assignment, in addition to screening for other associated features of each mutation. [ABSTRACT FROM AUTHOR]

The fission yeast Schizosaccharomyces pombe is an excellent model organism to explore cellular events owing to rich tools in genetics, molecular biology, cellular biology, and biochemistry. Schizosaccharomyces pombe proliferates continuously when nutrients are abundant but arrests in G1 phase upon depletion of nutrients such as nitrogen and glucose. When cells of opposite mating types are present, cells conjugate, fuse, undergo meiosis, and finally form 4 spores. This sexual differentiation process in S. pombe has been studied extensively. To execute sexual differentiation, the glucose-sensing cAMP-PKA (cyclic adenosine monophosphate-protein kinase A) pathway, nitrogen-sensing TOR (target of rapamycin) pathway, and SAPK (stress-activating protein kinase) pathway are crucial, and the MAPK (mitogen-activating protein kinase) cascade is essential for pheromone sensing. These signals regulate ste11 at the transcriptional and translational levels, and Ste11 is modified in multiple ways. This review summarizes the initiation of sexual differentiation in S. pombe based on results I have helped to obtain, including the work of many excellent researchers. [ABSTRACT FROM AUTHOR]

In ovo exposure to o,p′‐dichloro‐diphenyl‐trichloroethane (o,p′‐DDT) impairs reproduction by inducing malformation of the reproductive organs in birds, although the mechanism remains unclear. Here, we examined the effects of o,p′‐DDT on the development of the reproductive organs, the expression of genes controlling sexual differentiation, and the plasma concentrations of testosterone and estradiol in Japanese quail embryos. o,p′‐DDT‐containing sesame oil was injected into the yolk sac on Embryonic Day (E) 3 at a dose of 500, 2,000, or 8,000 μg per egg. On E15, the reproductive organs were observed; the gonads and Müllerian ducts (MDs) were sampled to measure the mRNA of steroidogenic enzymes, sex steroid receptors, anti‐Müllerian hormone (AMH), and AMH receptor 2 (AMHR2); blood samples were collected to assay plasma testosterone and estradiol levels; and the gonads were used for histological analysis. o,p′‐DDT dose‐dependently increased the prevalence of hypertrophic MDs in females and residual MDs in males. In female MDs, o,p′‐DDT dose‐dependently decreased estrogen receptor (ER) α, ERβ, and AMHR2 mRNA expression. o,p′‐DDT dose‐dependently induced left‐biased asymmetry of testis size, and ovary‐like tissue was found in the left testis after exposure to 8,000 μg per egg o,p′‐DDT, although asymmetric gene expression did not occur. o,p′‐DDT did not affect ovarian tissue but did decrease 17α‐hydroxylase/C17‐20 lyase mRNA expression and dose‐dependently increased ERβ mRNA expression. o,p′‐DDT decreased plasma testosterone concentrations in females. These findings suggest that o,p′‐DDT induces hypertrophy of the MDs and ovarian tissue formation in the left testis. Abnormal MD development may be linked to altered gene expression for sensing estrogens and AMH signals. The effects of in ovo exposure to o,p′‐dichloro‐diphenyl‐trichloroethane (o,p′‐DDT), a pesticide with estrogenic activity, on the morphology of and gene expression in the reproductive organs of Japanese quail embryos were examined. o,p′‐DDT induced Müllerian duct hypertrophy and decreased the mRNA expression of estrogen and anti‐Müllerian hormone receptors. o,p′‐DDT also induced testis size asymmetry and ovotestis formation. o,p′‐DDT may induce Müllerian duct hypertrophy and ovotestis formation via its endocrine‐disrupting actions. [ABSTRACT FROM AUTHOR]

Abstract Papaya (Carica papaya) is a trioecious species with female, male, and hermaphrodite plants. Given the sex segregation, selecting hermaphroditic plants is vital for orchard establishment due to their greater commercial value. However, selecting hermaphrodite plants through sexing is laborious and costly. Moreover, environmental stressors can exacerbate the issue by potentially inducing abnormal flower development, thus affecting fruit quality. Despite these challenges, the molecular mechanisms governing sex development in papaya remain poorly understood. Thus, this study aimed to identify proteins associated with sex development in female and hermaphrodite flowers of papaya through comparative proteomic analysis. Proteins from flower buds at the early and late developmental stages of three papaya genotypes (UENF-CALIMAN 01, JS12, and Sunrise Solo 72/12) were studied via proteomic analysis via the combination of the shotgun method and nanoESI-HDMSE technology. In buds at an early stage of development, 496 (35.9%) proteins exhibited significantly different abundances between sexes for the SS72/12 genotype, 139 (10%) for the JS12 genotype, and 165 (11.9%) for the UC-01 genotype. At the final stage of development, there were 181 (13.5%) for SS72/12, 113 (8.4%) for JS12, and 125 (9.1%) for UC-01. The large group of differentially accumulated proteins (DAPs) between the sexes was related to metabolism, as shown by the observation of only the proteins that exhibited the same pattern of accumulation in the three genotypes. Specifically, carbohydrate metabolism proteins were up-regulated in hermaphrodite flower buds early in development, while those linked to monosaccharide and amino acid metabolism increased during late development. Enrichment of sporopollenin and phenylpropanoid biosynthesis pathways characterizes hermaphrodite samples across developmental stages, with predicted protein interactions highlighting the crucial role of phenylpropanoids in sporopollenin biosynthesis for pollen wall formation. Most of the DAPs played key roles in pectin, cellulose, and lignin synthesis and were essential for cell wall formation and male flower structure development, notably in the pollen coat. These findings suggest that hermaphrodite flowers require more energy for development, likely due to complex pollen wall formation. Overall, these insights illuminate the molecular mechanisms of papaya floral development, revealing complex regulatory networks and energetic demands in the formation of male reproductive structures.

Abstract Meiosis is a specialized type of cell division that occurs physiologically only in germ cells. We previously demonstrated that MYC-associated factor X (MAX) blocks the ectopic onset of meiosis in embryonic and germline stem cells in culture systems. Here, we investigated the Max gene’s role in mouse primordial germ cells. Although Max is generally ubiquitously expressed, we revealed that sexually undifferentiated male and female germ cells had abundant MAX protein because of their higher Max gene expression than somatic cells. Moreover, our data revealed that this high MAX protein level in female germ cells declined significantly around physiological meiotic onset. Max disruption in sexually undifferentiated germ cells led to ectopic and precocious expression of meiosis-related genes, including Meiosin, the gatekeeper of meiotic onset, in both male and female germ cells. However, Max-null male and female germ cells did not complete the entire meiotic process, but stalled during its early stages and were eventually eliminated by apoptosis. Additionally, our meta-analyses identified a regulatory region that supports the high Max expression in sexually undifferentiated male and female germ cells. These results indicate the strong connection between the Max gene and physiological onset of meiosis in vivo through dynamic alteration of its expression.

Papaya (Carica papaya) is a trioecious species with female, male, and hermaphrodite plants. Given the sex segregation, selecting hermaphroditic plants is vital for orchard establishment due to their greater commercial value. However, selecting hermaphrodite plants through sexing is laborious and costly. Moreover, environmental stressors can exacerbate the issue by potentially inducing abnormal flower development, thus affecting fruit quality. Despite these challenges, the molecular mechanisms governing sex development in papaya remain poorly understood. Thus, this study aimed to identify proteins associated with sex development in female and hermaphrodite flowers of papaya through comparative proteomic analysis. Proteins from flower buds at the early and late developmental stages of three papaya genotypes (UENF-CALIMAN 01, JS12, and Sunrise Solo 72/12) were studied via proteomic analysis via the combination of the shotgun method and nanoESI-HDMSE technology. In buds at an early stage of development, 496 (35.9%) proteins exhibited significantly different abundances between sexes for the SS72/12 genotype, 139 (10%) for the JS12 genotype, and 165 (11.9%) for the UC-01 genotype. At the final stage of development, there were 181 (13.5%) for SS72/12, 113 (8.4%) for JS12, and 125 (9.1%) for UC-01. The large group of differentially accumulated proteins (DAPs) between the sexes was related to metabolism, as shown by the observation of only the proteins that exhibited the same pattern of accumulation in the three genotypes. Specifically, carbohydrate metabolism proteins were up-regulated in hermaphrodite flower buds early in development, while those linked to monosaccharide and amino acid metabolism increased during late development. Enrichment of sporopollenin and phenylpropanoid biosynthesis pathways characterizes hermaphrodite samples across developmental stages, with predicted protein interactions highlighting the crucial role of phenylpropanoids in sporopollenin biosynthesis for pollen wall formation. Most of the DAPs played key roles in pectin, cellulose, and lignin synthesis and were essential for cell wall formation and male flower structure development, notably in the pollen coat. These findings suggest that hermaphrodite flowers require more energy for development, likely due to complex pollen wall formation. Overall, these insights illuminate the molecular mechanisms of papaya floral development, revealing complex regulatory networks and energetic demands in the formation of male reproductive structures. [ABSTRACT FROM AUTHOR]

The Masculinizer gene, Masc, encodes a lepidopteran‐specific novel CCCH‐type zinc finger protein, which controls sex determination and dosage compensation in Bombyx mori. Considering the potential application of it in pest control, it is necessary to investigate the function of Masc gene in Hyphantria cunea, a globally invasive forest pest. In the present study, we identified and functionally characterized the Masc gene, HcMasc, in H. cunea. Sequence analysis revealed that HcMASC contained the conserved CCCH‐type zinc finger domain, nuclear localization signal, and male determining domain, in which the last was confirmed to be required for its masculinization in BmN cell line. However, expression data showed that unlike male‐biased expression in B. mori, HcMasc gene expresses in main all developmental stages or tissues in both sexes. Clustered regularly interspaced palindromic repeats (CRISPR) / CRISPR‐associated protein 9‐based disruption of the common exons 1 and 3 of the HcMasc gene resulted in imbalanced sex ratio and abnormal external genitalia of both sexes. Our results suggest that the HcMasc gene is required for both male and female sexual differentiation and dosage compensation in H. cunea and provide a foundation for developing better strategies to control this pest. [ABSTRACT FROM AUTHOR]

The neuroendocrine system that controls the preovulatory surge of gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH), which triggers ovulation in female mammals, is sexually differentiated in rodents. A transient increase in circulating testosterone levels in male rats within a few hours of birth is primarily responsible for the defeminization of anteroventral periventricular nucleus (AVPV) kisspeptin neurons, which are critical regulators of the GnRH/LH surge. The present study aimed to determine whether neonatal estradiol-17β (E2) converted from testosterone by aromatase primarily causes the defeminization of AVPV kisspeptin neurons and the surge of GnRH/LH in male rodents. The results of the present study showed that the neonatal administration of letrozole (LET), a nonsteroidal aromatase inhibitor, within 2 hours of birth rescued AVPV Kiss1 expression and the LH surge in adult male rats, while the neonatal administration of testosterone propionate (TP) irreversibly attenuated AVPV Kiss1 expression and the LH surge in adult female rats. Furthermore, the neonatal LET-treated Kiss1 - Cre –activated tdTomato reporter males exhibited a comparable number of AVPV Kiss1 - Cre –activated tdTomato-expressing cells to that of vehicle-treated female rats, while neonatal TP-treated females showed fewer AVPV Kiss1 - Cre –activated tdTomato-expressing cells than vehicle-treated females. Moreover, neonatal TP administration significantly decreased the number of arcuate Kiss1 -expressing and Kiss1 - Cre –activated tdTomato-positive cells and suppressed LH pulses in adult gonadectomized female rats; however, neonatal LET administration failed to affect them. These results suggest that E2 converted from neonatal testosterone is primarily responsible for the defeminization of AVPV kisspeptin neurons and the subsequent GnRH/LH surge generation in male rats. [ABSTRACT FROM AUTHOR]

Meiosis is a specialized type of cell division that occurs physiologically only in germ cells. We previously demonstrated that MYC-associated factor X (MAX) blocks the ectopic onset of meiosis in embryonic and germline stem cells in culture systems. Here, we investigated the Max gene's role in mouse primordial germ cells. Although Max is generally ubiquitously expressed, we revealed that sexually undifferentiated male and female germ cells had abundant MAX protein because of their higher Max gene expression than somatic cells. Moreover, our data revealed that this high MAX protein level in female germ cells declined significantly around physiological meiotic onset. Max disruption in sexually undifferentiated germ cells led to ectopic and precocious expression of meiosis-related genes, including Meiosin, the gatekeeper of meiotic onset, in both male and female germ cells. However, Max-null male and female germ cells did not complete the entire meiotic process, but stalled during its early stages and were eventually eliminated by apoptosis. Additionally, our meta-analyses identified a regulatory region that supports the high Max expression in sexually undifferentiated male and female germ cells. These results indicate the strong connection between the Max gene and physiological onset of meiosis in vivo through dynamic alteration of its expression. [ABSTRACT FROM AUTHOR]

We previously showed that the anti-Müllerian hormone (AMH), infiltrating from the testis to the mesonephros reaches the cranial and middle regions of the Müllerian duct (MD) and induces their regression using an organ culture in mice. However, it is difficult to maintain structural integrity, such as the length and diameter and normal direction of elongation of the caudal region of the MD, in conventional organ culture systems. Therefore, the pathway of AMH to the caudal MD region remains uncharted. In this study, we established an organ culture method that can maintain the morphology of the caudal region of the MD. The gonad--mesonephros complex, metanephros, and urinary bladder of mouse fetuses at 12.5 dpc attached to the body trunk were cultured on agarose gels for 72 hr. The cultured caudal region of the mesonephros was elongated along the body trunk, and the course of the mesonephros was maintained in many individuals. In males, mesenchymal cells aggregated around the MD after culture. Moreover, the male MD diameter was significantly smaller than the female. Based on these results, it was concluded that the development of the MD was maintained in the present organ culture system. Using this culture system, AMH infiltration to the caudal region of the MD can be examined without the influence of AMH in the blood. This culture system is useful for clarifying the regression mechanism of the caudal region of the MD. [ABSTRACT FROM AUTHOR]

Background: The Müllerian duct (MD), the primordium of the female reproductive tract, is also formed in males during the early stage of development, then regresses due to the anti‐Müllerian hormone (AMH) secreted from the testes. However, the detailed diffusion pathway of AMH remains unclear. We herein investigated the mechanism by which AMH reaches the middle region of the MD using an organ culture system. Results: Injection of recombinant human AMH into the testis around the start of MD regression induced diffuse immunoreactivity in the mesonephros near the injection site. When the testis and mesonephros were cultured separately, the diameters of both cranial and middle MDs were significantly increased compared to the control. In the testis–mesonephros complex cultured by inhibiting the diffusion of AMH through the cranial region, the cranial MD diameter was significantly increased compared to the control, and there was no difference in middle MD diameter. Conclusions: These results indicate that AMH, which infiltrates from the testis through the cranial region at physiological concentrations, induces regression of the cranial MD at the start of MD regression. They also indicate that AMH infiltrating through the caudal regions induces regression of the middle MD. Key Findings: In the early stage of Müllerian duct (MD) regression, testicular anti‐Müllerian hormone (AMH) reaches the vicinity of the MD without the circulatory system.AMH infiltrates the mesonephros from the region between the testis and the mesonephros.AMH infiltrating from the testis regresses both cranial MD and middle MD. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Guangxi Normal University - Natural Science Edition is the property of Gai Kan Bian Wei Hui and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Müllerian ducts are paired embryonic tubes that give rise to the female reproductive tract. In humans, the Müllerian ducts differentiate into the Fallopian tubes, uterus and upper portion of the vagina. In birds and reptiles, the Müllerian ducts develop into homologous structures, the oviducts. The genetic and hormonal regulation of duct development is a model for understanding sexual differentiation. In males, the ducts typically undergo regression during embryonic life, under the influence of testis-derived Anti-Müllerian Hormone, AMH. In females, a lack of AMH during embryogenesis allows the ducts to differentiate into the female reproductive tract. In the chicken embryo, a long-standing model for development and sexual differentiation, Müllerian duct development in females in asymmetric. Only the left duct forms an oviduct, coincident with ovary formation only on the left side of the body. The right duct, together with the right gonad, becomes vestigial. The mechanism of this avian asymmetry has never been fully resolved, but is thought to involve local interplay between AMH and sex steroid hormones. This mini-review re-visits the topic, highlighting questions in the field and proposing a testable model for asymmetric duct development. We argue that current molecular and imaging techniques will shed new light on this curious asymmetry. Information on asymmetric duct development in the chicken model will inform our understanding of sexual differentiation in vertebrates more broadly. [ABSTRACT FROM AUTHOR]

Senescence is the irreversible decline in physiological functioning and survival with age. While this phenomenon has been studied in a range of different taxa, including seabirds, it has seldom been assessed for both sexes of monomorphic species, and in conservation contexts. Here, we studied the effect of age and sex on the foraging trip characteristics and energetics of the monomorphic Cape gannet (Morus capensis). Between 2017 and 2020, we used GPS recorders and miniaturised three-dimensional accelerometers to obtain data on the foraging trip characteristics and energy expenditure of 39 Cape gannets rearing chicks on Malgas Island, South Africa. This sample included 11 females and 28 males between the ages of 4 and 23 years. No difference in foraging trip characteristics was apparent between sexes or individuals of different ages. The energy expenditure of aging females (> 17 years) was higher than that of aging males. Aging females spent both more energy flying and less energy resting than males, despite similar foraging trip durations and distances. Males spent more energy diving and taking off from the water than females. The age-related sexual differences in energy expenditure presented in our study might reflect niche and/or risk partitioning strategies to ensure adequate provisioning to the chick, or a possible earlier onset of senescence in females relative to males. The higher energy expenditure of aging females, which presumably requires a concomitantly higher energy intake, likely reduces their resilience to environmental change. [ABSTRACT FROM AUTHOR]

Introduction: Women are more vulnerable to cocaine's reinforcing effects and have a more rapid course to addiction after initial cocaine use as compared to men. Studies in rodents similarly indicate an enhanced sensitivity to the reinforcing effects of cocaine in females versus males. Levels of estradiol (E2) are correlated with vulnerability to the rewarding actions of cocaine. Here, we asked if sex chromosome complement (SCC) influences vulnerability to cocaine use. Methods: We used the four-core genotype mouse that produces gonadal males and females with either XX or XY SCC. Mice were gonadectomized and implanted with either an estradiol (E2) or cholesterol-filled pellet. This allowed us to determine the effects of SCC in the absence (cholesterol-treated) and presence of tonic high physiological hormone levels (estradiol). Acquisition of cocaine self-administration was determined over a 12-day period using an escalated dose procedure (0.3 mg/kg/infusion, sessions 1–6; 0.6 mg/kg/infusion, sessions 6–12). Results: Without estradiol treatment, a greater percentage of castrated XY mice acquired cocaine self-administration and did so at a faster rate than XX castrates and ovariectomized XY females. These same XY males acquired sooner, infused more cocaine, and directed more nose pokes to the rewarded nose-poke hole than XX castrates and XY males receiving E2. Conclusion: Our results suggest that in gonadal male mice, SCC and estradiol can modulate the reinforcing effects of cocaine which may influence the likelihood of cocaine use. [ABSTRACT FROM AUTHOR]

The neurohormone crustacean female sex hormone (CFSH) contains a highly conserved interleukin-17 (IL-17) domain in the mature peptide. Although CFSH has been demonstrated to stimulate female sexual differentiation in crustaceans, its receptors (CFSHR) have been poorly reported. The present study identified an IL-17 receptor (named Lvit-IL-17R), a candidate of CFSHR, from the protandric simultaneous hermaphroditic (PSH) shrimp Lysmata vittata through GST pulldown assays and RNAi experiments. Lvit-IL-17R is a transmembrane protein with an SEFIR (similar expression as the fibroblast growth factor and IL-17R) domain, as determined through sequence analysis. A GST pulldown experiment confirmed the interactions between the type I CFSHs (CFSH1a and CFSH1b) and Lvit-IL-17R. Meanwhile, the RNAi results revealed that Lvit-IL-17R displays similar functions to type I CFSHs in regulating sexual differentiation and gonad development. In brief, Lvit-IL-17R is a potential receptor for type I CFSHs aimed at regulating the sexual differentiation of the PSH species. This study helps shed new light on the mechanism of sexual differentiation among crustaceans. [ABSTRACT FROM AUTHOR]

Despite the notable progress made in recent years, the understanding of the genetic control of gonadal sex differentiation and asymmetrical ovariogenesis in chicken during embryonic development remains incomplete. This study aimed to identify potential key genes and speculate about the mechanisms associated with ovary and testis development via an analysis of the results of PacBio and Illumina transcriptome sequencing of embryonic chicken gonads at the initiation of sexual differentiation (E4.5, E5.5, and E6.5). PacBio sequencing detected 328 and 233 significantly up-regulated transcript isoforms in females and males at E4.5, respectively. Illumina sequencing detected 95, 296 and 445 DEGs at E4.5, E5.5, and E6.5, respectively. Moreover, both sexes showed asymmetrical expression in gonads, and more DEGs were detected on the left side. There were 12 DEGs involved in cell proliferation shared between males and females in the left gonads. GO analysis suggested that coagulation pathways may be involved in the degradation of the right gonad in females and that blood oxygen transport pathways may be involved in preventing the degradation of the right gonad in males. These results provide a comprehensive expression profile of chicken embryo gonads at the initiation of sexual differentiation, which can serve as a theoretical basis for further understanding the mechanism of bird sex determination and its evolutionary process. [ABSTRACT FROM AUTHOR]

We previously demonstrated that treating fetal lambs on gestational day 62 with the long-acting gonadotrophin-releasing hormone (GnRH) antagonist degarelix (DG) suppresses pituitary-testicular function during midgestation. The objective of this study was to investigate whether impaired gonadotrophic drive during this fetal period has enduring effects on sexual differentiation and reproductive function in adult male sheep. We assessed the effects of prenatal administration of DG, with or without testosterone (T) replacement, on various sexually dimorphic behavioral traits in adult rams, including sexual partner preferences, as well as neuroendocrine responsiveness and testicular function. Our findings revealed that DG treatment had no effect on genital differentiation or somatic growth. There were some indications that DG treatment suppressed juvenile play behavior and adult sexual motivation; however, male-typical sexual differentiation of reproductive behavior, sexual partner preference, and gonadotropin feedback remained unaffected and appeared to be fully masculinized and defeminized. DG-treated rams showed an increased LH response to GnRH stimulation and a decreased T response to human chorionic gonadotropin stimulation, suggesting impaired Leydig cell function and reduced T feedback. Both effects were reversed by cotreatment with T propionate. DG treatment also suppressed the expression of CYP17 messenger RNA, a key enzyme for T biosynthesis. Despite the mild hypogonadism induced by DG treatment, ejaculate volume, sperm motility, and sperm morphology were not affected. In summary, these results suggest that blocking GnRH during midgestation does not have enduring effects on brain sexual differentiation but does negatively affect the testes' capacity to synthesize T. [ABSTRACT FROM AUTHOR]

The formation of Wolffian ducts (WDs) includes three highly coordinated developmental stages, specification, elongation, and maintenance, prior to sexual differentiation. After their initial formation in both sexes, the WD epithelium and mesenchyme have sexually dimorphic fates depending on the presence of androgen action and local genetic programs. Postnatal differentiation of the epithelial lineage into principal, basal, and clear cells is controlled by androgens, lumicrine, and local factors. A lineage progression for epithelial cells is established. Aberrant cell differentiation is one underlying cause of WD abnormalities and associated pathologies in both men and women. Wolffian ducts (WDs) are the paired embryonic structures that give rise to internal male reproductive tract organs. WDs are initially formed in both sexes but have sex-specific fates during sexual differentiation. Understanding WD differentiation requires insights into the process of fate decisions of epithelial and mesenchymal cells, which are tightly coordinated by endocrine, paracrine, and autocrine signals. In this review, we discuss current advances in understanding the fate-decision process of WD epithelial and mesenchymal lineages from their initial formation at the embryonic stage to postnatal differentiation. Finally, we discuss aberrant cell differentiation in WD abnormalities and pathologies and identify opportunities for future investigations. [ABSTRACT FROM AUTHOR]

The spotted hyaena (Crocuta crocuta) is a unique species, even amongst the Hyaenidae. Extreme clitoral development in female spotted hyaenas challenges aspects of the accepted framework of sexual differentiation and reproductive function. They lack a vulva and instead urinate, copulate and give birth through a single, long urogenital canal that traverses a clitoris superficially resembling a penis. Recent and historical evidence is reviewed to describe our changing understanding of the biology of this species. Expanding upon observations from hyaenas in nature, much has been learned from studies utilising the captive colony at the University of California, Berkeley. The steroid environment of pregnancy is shaped by placental androgen and oestrogen secretion and a late gestational increase in sex hormone binding globulin, the regulated expression and steroid-binding characteristics of which are unique within the Hyaenidae. While initial external genital development is largely free of androgenic influence, the increase in testosterone concentrations in late gestation influences foetal development. Specifically, anti-androgen (AA) treatment of pregnant females reduced the developmental influence of androgens on their foetuses, resulting in reduced androstenedione concentrations in young females and easier birth through a 'feminised' clitoris, but precluded intromission and mating by 'feminised' male offspring, and altered social interactions. Insight into the costs and benefits of androgen exposure on spotted hyaena reproductive development, endocrinology and behaviour emphasises the delicate balance that sustains reproductive success, forces a re-evaluation of how we define masculine vs feminine sexual characteristics, and motivates reflection about the representative value of model species.

Autism spectrum disorder (ASD) is associated with the altered functional connectivity of 3 neurocognitive networks that are hypothesized to be central to the symptomatology of ASD: the salience network (SN), default mode network (DMN), and central executive network (CEN). Due to the considerably higher prevalence of ASD in males, however, previous studies examining these networks in ASD have used primarily male samples. It is thus unknown how these networks may be differentially impacted among females with ASD compared to males with ASD, and how such differences may compare to those observed in neurotypical individuals. Here, we investigated the functional connectivity of the SN, DMN, and CEN in a large, well-matched sample of girls and boys with and without ASD (169 youth, ages 8-17). Girls with ASD displayed greater functional connectivity between the DMN and CEN than boys with ASD, whereas typically developing girls and boys differed in SN functional connectivity only. Together, these results demonstrate that youth with ASD exhibit altered sex differences in these networks relative to what is observed in typical development, and highlight the importance of considering sex-related biological factors and participant sex when characterizing the neural mechanisms underlying ASD.

The behavioural ecology of host species is likely to affect their microbial communities, because host sex, diet, physiology, and movement behaviour could all potentially influence their microbiota. We studied a wild population of barn owls (Tyto alba) and collected data on their microbiota, movement, diet, size, coloration, and reproduction. The composition of bacterial species differed by the sex of the host and female owls had more diverse bacterial communities than their male counterparts. The abundance of two families of bacteria, Actinomycetaceae and Lactobacillaceae, also varied between the sexes, potentially as a result of sex differences in hormones and immunological function, as has previously been found with Lactobacillaceae in the microbiota of mice. Male and female owls did not differ in the prey they brought to the nest, which suggests that dietary differences are unlikely to underlie the differences in their microbiota. The movement behaviour of the owls was associated with the host microbiota in both males and females because owls that moved further from their nest each day had more diverse bacterial communities than owls that stayed closer to their nests. This novel result suggests that the movement ecology of hosts can impact their microbiota, potentially on the basis of their differential encounters with new bacterial species as the hosts move and forage across the landscape. Overall, we found that many aspects of the microbial community are correlated with the behavioural ecology of the host and that data on the microbiota can aid in generating new hypotheses about host behaviour.

This paper is part of the celebration of the 50th anniversary of founding of the journal Hormones and Behavior, the official journal of the Society for Behavioral Neuroendocrinology. All sex differences in phenotypic development stem from the sexual imbalance in X and Y chromosomes, which are the only known differences in XX and XY zygotes. The sex chromosome genes act within cells to cause differences in phenotypes of XX and XY cells throughout the body. In the gonad, they determine the type of gonad, leading to differences in secretion of testicular vs. ovarian hormones, which cause further sex differences in tissue function. These current ideas of sexual differentiation are briefly contrasted with a hormones-only view of sexual differentiation of the last century. The multiple, independent action of diverse sex-biasing agents means that sex-biased factors can be synergistic, increasing sex differences, or compensatory, making the two sexes more equal. Several animal models have been fruitful in demonstrating sex chromosome effects, and interactions with gonadal hormones. MRI studies of human brains demonstrate variation in brain structure associated with both differences in gonadal hormones, and in the number of X and Y chromosomes. Five unanswered questions are posed as a challenge to future investigators to improve understanding of sexual differentiation throughout the body.

In addition to their role in the breakdown of H 2 O 2 , some peroxiredoxins (Prxs) have chaperone and H 2 O 2 sensing functions. Acting as an H 2 O 2 sensor, Prx Gpx3 transfers the oxidant signal to the transcription factor Yap1, involved in the antioxidant response in Saccharomyces cerevisiae. We have shown that Aspergillus nidulans Yap1 ortholog NapA is necessary for the antioxidant response, the utilization of arabinose, fructose and ethanol, and for proper development. To address the Prx roles in these processes, we generated and characterized mutants lacking peroxiredoxins PrxA, PrxB, PrxC, or TpxC. Our results show that the elimination of peroxiredoxins PrxC or TpxC does not produce any distinguishable phenotype. In contrast, the elimination of atypical 2-cysteine peroxiredoxins PrxA and PrxB produce different mutant phenotypes. ΔprxA , ΔnapA and ΔprxA ΔnapA mutants are equally sensitive to H 2 O 2 and menadione, while PrxB is dispensable for this. However, the sensitivity of ΔprxA and ΔprxA ΔnapA mutants is increased by the lack of PrxB. Moreover, PrxB is required for arabinose and ethanol utilization and fruiting body cell wall pigmentation. PrxA expression is partially independent of NapA, and the replacement of peroxidatic cysteine 61 by serine (C61S) is enough to cause oxidative stress sensitivity and prevent NapA nuclear accumulation in response to H 2 O 2 , indicating its critical role in H 2 O 2 sensing. Our results show that despite their high similarity, PrxA and PrxB play differential roles in Aspergillus nidulans antioxidant response, carbon utilization and development. [ABSTRACT FROM AUTHOR]

A variety of intestinal-derived culture systems have been developed to mimic in vivo cell behavior and organization, incorporating different tissue and microenvironmental elements. Great insight into the biology of the causative agent of toxoplasmosis, Toxoplasma gondii, has been attained by using diverse in vitro cellular models. Nonetheless, there are still processes key to its transmission and persistence which remain to be elucidated, such as the mechanisms underlying its systemic dissemination and sexual differentiation both of which occur at the intestinal level. Because this event occurs in a complex and specific cellular environment (the intestine upon ingestion of infective forms, and the feline intestine, respectively), traditional reductionist in vitro cellular models fail to recreate conditions resembling in vivo physiology. The development of new biomaterials and the advances in cell culture knowledge have opened the door to a next generation of more physiologically relevant cellular models. Among them, organoids have become a valuable tool for unmasking the underlying mechanism involved in T. gondii sexual differentiation. Murine-derived intestinal organoids mimicking the biochemistry of the feline intestine have allowed the generation of pre-sexual and sexual stages of T. gondii for the first time in vitro, opening a window of opportunity to tackling these stages by "felinizing" a wide variety of animal cell cultures. Here, we reviewed intestinal in vitro and ex vivo models and discussed their strengths and limitations in the context of a quest for faithful models to in vitro emulate the biology of the enteric stages of T. gondii. [ABSTRACT FROM AUTHOR]

Sex hormones and genes on the sex chromosomes are not only key factors in the regulation of sexual differentiation and reproduction but they are also deeply involved in brain homeostasis. Their action is crucial for the development of the brain, which presents different characteristics depending on the sex of individuals. The role of these players in the brain is fundamental in the maintenance of brain function during adulthood as well, thus being important also with respect to age-related neurodegenerative diseases. In this review, we explore the role of biological sex in the development of the brain and analyze its impact on the predisposition toward and the progression of neurodegenerative diseases. In particular, we focus on Parkinson's disease, a neurodegenerative disorder that has a higher incidence in the male population. We report how sex hormones and genes encoded by the sex chromosomes could protect from the disease or alternatively predispose toward its development. We finally underline the importance of considering sex when studying brain physiology and pathology in cellular and animal models in order to better understand disease etiology and develop novel tailored therapeutic strategies. [ABSTRACT FROM AUTHOR]

Sphaeropteris lepifera (J.Sm. ex Hook.) R. M. Tryon is a rare and endangered tree fern. 5-azacytidine (5-azaC), an inhibitor of DNA methylation, promotes male gametophyte differentiation and increases the abundance of antheridia. To explore the relationship between DNA methylation and sex differentiation in S. lepifera, RNA sequencing was performed to analyze the transcriptome of 5-azaC-treated S. lepifera gametophytes. RNA-seq yielded a total of 39.16 Gb clean data, and 56,349 unigenes were obtained. Functional annotation of the unigenes was achieved by comparison to the Nr, Swiss-Prot, KEGG, COG, KOG, GO, and Pfam databases. In total, 26,744 unigenes annotation results were obtained. A total of 1091 differentially expressed genes (372 upregulated, 719 downregulated) were screened. A total of 351 genes were annotated using the KEGG database, and 60 pathways were involved. The four pathways containing the most differentially expressed genes were related to ribosomes, plant hormone signal transduction, starch and sucrose metabolism, and phenylpropane biosynthesis. Expression analysis of 17 genes in male and female S. lepifera gametophytes and in S. lepifera gametophytes under 5-azaC treatment was performed. We identified four genes that can be used to further explore the relationship between DNA methylation and sex differentiation in S. lepifera. [ABSTRACT FROM AUTHOR]

[Objective] The paper aims to explore whether calmodulin-like CMLs participate in the sexual differentiation process in Cucumis sativus L., so as to provide reference for improving the regulatory network of sexual differentiation furtherly. [Method] In the study, CMLS, ACSIG, ACS2 and ACS11 genes of cucumber were cloned, qPCR was used to detect the expressions of CMLS gene in different types of the flowers, and the interactions between CMLS and proteins encoded by major genes of cucumber sex differentiation were detected by the method of yeast two-hybrid. [Result】 CML8 was cloned from cucumber which contained a complete ORF of 441 bp, encoding 146 aa without signal peptide. It was an extracellular protein without transmembrane domain and introns, and contained 4 EF-hand domains with Ca2+ binding ca- pacity, and subcellular was located in cell membrane and cytoplasm. ACSIG, ACS2 and ACSII, three key genes of cucumber sexual differ- entiation were cloned, and sequence alignment showed that the nucleotide sequences and encoded protein sequences of the three genes were consistent with those in the cucumber database. There were significant differences in the expression levels of three genes in the female flow- ers, male flowers and bisexual flowers, and extremely significant differences in male flowers. The yeast two-hybrid experiment showed that CMLS could interact with ACSIG and ACS2, but not with ACS11. [Conclusion] Calmodulin-like 8 (CMLS) was cloned, and CMLS could interact with ACSIG and ACS2, which might participate in the sexual differentiation of cucumber, and the study was the first time to explore the involvement of calmodulin in the process of plant sexual differentiation, and expect to provide reference for calcium signaling system to participate in the process of plant sexual differentiation. [ABSTRACT FROM AUTHOR]

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