Development Of Reproductive System Research Articles

Distribution of cytoskeletal proteins in the cat testis during the pre-pubertal and post-pubertal periods

Cytoskeletal proteins not only define the shape of cells, but also have critical roles in their proliferation, migration and motility, as well as in the establishment and maintenance of tissue organization and integrity. Furthermore, these proteins influence the physiological processes of the male reproductive system and are found in the structure of some cells. This study aimed to determine differences between the pre- and post-pubertal periods for the localization and distribution of actin, desmin, vimentin and cytokeratin-18 in the testes, epididymides and ductus deferentes of Persian and Turkish Angora and Van cats, using immunohistochemistry. The study material was grouped as belonging to the pre-pubertal and post-pubertal periods. The tissue samples of both groups were subjected to routine histological processing and embedded in paraffin. Serial sections cut from the paraffin-embedded tissue blocks were immunohistochemically stained with the indirect streptavidin-biotin complex method. Immunohistochemical findings demonstrated that there was no difference between the pre- and post-pubertal periods for the staining intensity and distribution of the proteins actin, vimentin, desmin and cytokeratin-18 in Persian and Turkish Angora and Van cats. On the other hand, differences were detected between the pre- and post-pubertal periods for the cellular expression and localization of these proteins in the testes, epididymides and ductus deferentes. Thus, the study results suggest that, based on the expression of actin, desmin, vimentin and cytokeratin-18 in the testes, epididymides and ductus deferentes during both periods, these molecular factors could have a contributory role in the development of the male reproductive system and the regulation of its physiological processes.

Exposure to Low Zearalenone Doses and Changes in the Homeostasis and Concentrations of Endogenous Hormones in Selected Steroid-Sensitive Tissues in Pre-Pubertal Gilts.

This study was undertaken to analyze whether prolonged exposure to low-dose zearalenone (ZEN) mycotoxicosis affects the concentrations of ZEN, α-zearalenol (α-ZEL), and β-zearalenol (β-ZEL) in selected reproductive system tissues (ovaries, uterine horn-ovarian and uterine sections, and the middle part of the cervix), the hypothalamus, and pituitary gland, or the concentrations of selected steroid hormones in pre-pubertal gilts. For 42 days, gilts were administered per os different ZEN doses (MABEL dose [5 µg/kg BW], the highest NOAEL dose [10 µg/kg BW], and the lowest LOAEL dose [15 µg/kg BW]). Tissue samples were collected on days seven, twenty-one, and forty-two of exposure to ZEN (exposure days D1, D2, and D3, respectively). Blood for the analyses of estradiol and progesterone concentrations was collected in vivo on six dates at seven-day intervals (on analytical dates D1-D6). The analyses revealed that both ZEN and its metabolites were accumulated in the examined tissues. On successive analytical dates, the rate of mycotoxin accumulation in the studied tissues decreased gradually by 50% and proportionally to the administered ZEN dose. A hierarchical visualization revealed that values of the carry-over factor (CF) were highest on exposure day D2. In most groups and on most exposure days, the highest CF values were found in the middle part of the cervix, followed by the ovaries, both sections of the uterine horn, and the hypothalamus. These results suggest that ZEN, α-ZEL, and β-ZEL were deposited in all analyzed tissues despite exposure to very low ZEN doses. The presence of these undesirable compounds in the examined tissues can inhibit the somatic development of the reproductive system and compromise neuroendocrine coordination of reproductive competence in pre-pubertal gilts.

Pathogenicity evaluation of GVI-1 lineage infectious bronchitis virus and its long-term effects on reproductive system development in SPF hens.

Infectious bronchitis virus (IBV) has gained increasing attention in the poultry industry due to its ability to cause tissue injuries not only in the respiratory system and kidney but also in the reproductive system of layers. Recently, the GVI-1 lineage IBVs have spread widely in China, whereas their pathogenicity in egg-laying chickens has rarely been studied, especially its long-term influence in egg production upon the early infection in chicks. In this study, 10-day-old SPF chicks were infected with the GVI-1 lineage JX181 strain and monitored over a 170-day period after infection. The pathogenicity evaluation of the JX181 strain included clinical observations, immunohistochemical assay, viral load, viral shedding, gross autopsy, and laying rate. The results showed that JX181 has a high pathogenicity, causing severe system lesions, and the decrease in egg production. In summary, this study describes the long-term damages caused by the early infection with the IBV GVI-1 lineage on the reproductive system of hens, providing a comprehensive understanding of the pathogenicity of the IBV GVI-1 lineage and emphasizing the importance of its early prevention.

PDGF-AA activates AKT and ERK signaling for testicular interstitial Leydig cell growth via primary cilia.

Testes control the development of male reproductive system. The testicular interstitial Leydig cells (Leydig cells) synthesize testosterone for promoting spermatogenesis and secondary sexual characteristics. Type A platelet-derived growth factor (PDGF-AA) is one of the most important growth factors in regulating Leydig cell growth and function. Knockout of PDGF-AA or its congenital receptor PDGFR-α leads to poor testicular development caused by reducing Leydig cell numbers, supporting PDGF-AA/PDGFR-α signaling regulates Leydig cell development. Primary cilium is a cellular antenna that functions as an integrative platform to transduce extracellular signaling for proper development and differentiation. Several receptors including PDGFR-α are observed on primary cilia for initiating signaling cascades in distinct cell types. Here we showed that PDGF-AA/PDGFR-α signaling promoted Leydig cells growth, migration, and invasion via primary cilia. Upon PDGF-AA treatment, AKT and ERK signaling were activated to regulate these cellular events. Interestingly, active AKT and ERK were detected around the base of primary cilia. Depletion of ciliary genes (IFT88 and CEP164) alleviated PDGF-AA-activated AKT and ERK, thus reducing Leydig cell growth, migration, and invasion. Thus, our study not only reveals the function of PDGF-AA/PDGFR-α signaling in maintaining testicular physiology but also uncovers the role of primary cilium and downstream signaling in regulating Leydig cell development.

Effects of Elevated Maternal Adiposity on Offspring Reproductive Health: A Perspective From Epidemiologic Studies.

One in seven couples in developed countries suffers from infertility. Maternal overweight or obesity have detrimental and lasting effects on offspring cardiometabolic health, and although substantially more data are needed, hormonal imbalances in utero resulting from excessive maternal adiposity could also disrupt reproductive programming and affect the future reproductive health of offspring. Therefore, this mini-review evaluates the human epidemiologic evidence that maternal overweight/obesity could be associated with poor reproductive health outcomes in offspring. We searched PubMed for relevant studies using terms such as "maternal obesity" and "reproductive development." While the human epidemiologic literature is limited, studies have thus far observed that maternal obesity is associated with disrupted external genital development and several other markers of reproductive health across the lifespan. Specifically, maternal obesity is associated with higher risks of hypospadias and cryptorchidism in males and disrupted anogenital distance both in males and females. Maternal obesity has also been linked to earlier age at menarche in daughters, and precocious puberty in both sons and daughters. Finally, daughters of women with overweight or obesity have higher risks of developing polycystic ovarian syndrome, which has implications for fertility. This body of research suggests that in utero exposure to maternal obesity could disrupt reproductive system development, but substantially more evidence is needed, as almost no human epidemiologic studies have evaluated the long-term consequences of maternal obesity with regard to offspring fertility/fecundity.

Relationship between long-term use of Ritalin and semen parameters in patients referred to psychiatric centres.

Some studies have shown that Ritalin can interfere with the growth and development of the reproductive system and can also have a serious and harmful effect on sperm parameters, so we decided to conduct studies in this field on the human sample. In a case-control study, 100 adult men aged 21-31 years with hyperactivity were divided into two groups of 50 past users and 50 current users and, 50 patients who had not used Ritalin before were included as the control group. Data were analysed using SPSS software, version 20. Analysis of variance, Pearson correlation coefficient, and regression analysis was used to assess the correlation between variables. The results also showed that there was a statistically significant difference between the current users and the control group in terms of sperm count, abnormality, and motility (p< .47). Comparison of the user group in the past and the control group showed that there was no statistically significant difference in terms of sperm count (p< .59), but there was a significant difference in terms of sperm motility and abnormality between the two groups (p< .001). The present study showed that long-term use of Ritalin can have negative effects on sperm parameters in humans.

Post-embryonic development of the female reproductive system of the Neotropical termite Silvestritermes euamignathus (Isoptera: Termitidae: Syntermitinae)

In termites, the maturation of the female reproductive system is progressive following post-embryonic development. In Silvestritermes euamignathus, the imaginal line is characterized by five nymphal instars that develop into the imago, but it can deviate in some instars to neotenic reproductives. In order to understand the rate of development of the female reproductive system throughout post-embryonic development, we analyzed the morphology of the reproductive system of nymphs, characterizing the stage of development and comparing it with neotenics and primary queens. We also followed embryonic development and compared eggs from neotenics and primary queens from incipient and mature colonies. Our results showed that gonadal development follows the post-embryonic instars, and previtellogenic oocytes are present in third-instar nymphs and are retained for the next two successive nymphal instars. The full maturation of the ovaries with vitellogenic oocytes requires molting to either imagos or neotenics. Eggs from neotenics follow the same embryonic development and each stage presents similar volume when compared to those of mature primary queens. Eggs of primary queens from incipient colonies are greater in volume than those of mature primary queens and of neotenics, suggesting an investment in egg quality rather than quantity during colony foundation.

An interactive analysis of the mouse oviductal miRNA profiles.

MicroRNAs are small non-coding molecules that control several cellular functions and act as negative post-transcriptional regulators of the mRNA. While their implication in several biological functions is already known, an important role as regulators of different physiological and pathological processes in fertilization and embryo development is currently emerging. Indeed, miRNAs have been found in the oviductal fluid packaged within the extracellular vesicles, which might act as natural nanoshuttles by transporting lipids, proteins, RNA molecules and miRNAs from the oviduct to the gametes or embryos. Here, an exhaustive bibliography search was carried out, followed by the construction of a computational model based on the networks theory in an attempt to recreate and elucidate the pathways potentially activated by the oviductal miRNA. The omics data published to date were gathered to create the Oviductal MiRNome, in which the miRNA target genes and their interactions are represented by using stringApp and the Network analyzer from Cytoscape 3.7.2. Then, the hyperlinked nodes were identified to investigate the pathways in which they are involved using the gene ontology enrichment analysis. To study the phenotypical effects after the removal of key genes on the reproductive system and embryo, knockout mouse lines for every protein-coding gene were investigated by using the International Mouse Phenotyping Consortium database. The creation of the Oviductal MiRNome revealed the presence of important genes and their interactions within the network. The functional enrichment analysis revealed that the hyperlinked nodes are involved in fundamental cellular functions, both structural and regulatory/signaling, suggesting their implication in fertilization and early embryo development. This fact was as well evidenced by the effects of the gene deletion in KO mice on the reproductive system and embryo development. The present study highlights the importance of studying the miRNA profiles and their enormous potential as tools to improve the assisted reproductive techniques currently used in human and animal reproduction.

Modern opportunities and prospects for preserving woman’s health

Among the variety of factors that affect the female organism, obesity is of great importance in the formation, development and functioning of the reproductive system, the development of gynecological diseases in which metabolic syndrome plays an important pathogenetic role (polycystic ovary syndrome is diagnosed in 35-60% of obese women; menstrual dysfunction – in 6 times more often, primary infertility – 2 times more). The components of the metabolic syndrome have a significant effect on the body: insulin resistance, hyperinsulinemia, dyslipoproteinemia, elevated levels of thrombosis factors. This article reviews the current scientific literature on the role of sirtuins in the regulatory cellular processes and metabolic cascades, with special emphasis on the possibilities of their pharmacological activation by resveratrol. The role of resveratrol as a promoter of sirtuin activity at different levels of homeostasis disturbance was analyzed, and the properties of resveratrol, its effects and impact on the female body in the presence of metabolic pathology were analyzed in order to prescribe timely treatment and slow down the reproductive aging process.Literature data prove the importance of polyphenols (resveratrol) use as an effective and pathogenetically determined activator of sirtuins for the regulation of oxidative stress, inflammation, correction of dysbiosis and imbalance of the immune system in the concept of treatment of women with gynecological diseases and metabolic disorders. Resveratrol itself has a wide range of pharmacological effects with proven antilipogenic properties and a safe harmonizing estrogen-like effect on various regulatory levels. The natural plant composition and long history of use of resveratrol have repeatedly revealed its clinical achievements, including polycystic ovary syndrome treatment. The high clinical effectiveness and safety profile allow to recommend the inclusion of resveratrol in treatment regimens and to prevent the relapses of metabolically determined gynecological and somatic diseases in women of various age periods.

Continuous 17α-ethinylestradiol exposure impairs the sperm quality of marine medaka (Oryzias melastigma).

17α-ethinylestradiol (EE2) is an anthropogenic estrogen that is widely used for hormone therapy and oral contraceptives. It was reported that EE2 exposure induced reproductive impairments through processes affecting reproduction behavior and inducing ovotestis. However, the effects of continuous EE2 exposure on the reproductive performance remain largely unknown. In this study, adult marine medaka fish (Oryzias melastigma) were exposed to EE2 (85ng/L) for one (F0) and two (F1) generations. Our results indicate that continuous EE2 exposure reduced fecundity and sperm motility. The testicular transcriptome, followed by bioinformatic analysis revealed the dysregulation of pathways related to steroidogenesis, sperm motility, and reproductive system development. Collectively, our findings indicate that continuous EE2 exposure directly affected sperm quality via the alteration of steroidogenesis and dysregulation of reproductive system development. The identified key factors including DNM1, PINK1, PDE7B, and SLC12A7 can serve as biomarkers to assess EE2-reduced sperm motility.

Reproductive Development of Male Rats Exposed In Utero to Stress and/or Sertraline.

Despite increased prescription of sertraline during pregnancy, little is known about its action on reproductive development. Therefore, this study aimed to investigate the impact that stress, associated or not with sertraline, causes on the reproductive development of male rats. Pregnant Wistar rats were divided into 4 groups (n = 16/group): CO-received filtered water; SE-received 20 mg/kg sertraline; ST-submitted to restraint stress and received filtered water; SS-submitted to restraint stress and received sertraline. The treatment was carried out from gestational days (GDs) 13-20. The animals were euthanized on GD 20 (n = 8/group), postnatal day (PND) 45 (n = 8/group), and PND 110 (n = 8/group). The testes and epididymis were analyzed histologically, and immunohistochemistry was performed on the testes by proliferating cell nuclear antigen (PCNA) and the Wilms tumor protein (Wt1). Sperm quality was also analyzed on PND 110. The evolution of body weight, anogenital distance (AGD), and puberty installation day were also verified. Statistical analysis: 2-way ANOVA or Kruskal-Wallis test (p ≤ .05). Fetal testes presented a large number of acidophilic cells in the sertraline-exposed groups. The SS group also showed a decrease in the nuclear volume of Leydig cells. This same group showed low expression of PCNA and Wt1, decreased weight of the testes and epididymis, lower AGD, and delayed puberty installation. The adulthood groups exposed to sertraline presented alterations in sperm morphology and motility. The results demonstrated that prenatal exposure to sertraline compromises the development of the rat reproductive system.

Bisulfite-assisted surface Fenton-like degradation of dimethyl phthalate by ferrihydrite-H2O2 system

As a common plasticizer, phthalic acid esters (PAEs) have been widely employed to improve the flexibility and workability of polymetric materials, thus leading to their widespread distribution in soils and wastewater. Moreover, PAEs raised great public concerns due to their endocrine-disrupting effects, which could damage reproductive system and body development at low exposure dose. In the present study, a ferrihydrite-H2O2-bisulfite ternary system was developed to achieve efficient degradation of dimethyl phthalate (DMP). Our results showed that 86.6 % of total DMP could be removed within 240 min by the ferrihydrite-H2O2-bisulfite ternary system, in which the respective optimum concentration of ferrihydrite, H2O2 and bisulfite was set as 1.0 g/L, 5.0 mM and 2.0 mM. For comparison, negligible DMP removal was observed in the binary systems of ferrihydrite-H2O2, ferrihydrite-bisulfite and H2O2-bisulfite. Hydroxyl radical (•OH) was identified as the dominant reactive species for DMP degradation based on the results of electron paramagnetic resonance (EPR) analysis and free radicals quenching experiments. By complexing with iron species, bisulfite could accelerate the reduction of Fe(III) to Fe(II), thus increasing the generation of •OH by ∼4 times in the heterogeneous ferrihydrite-H2O2 system. Furthermore, ferrihydrite exhibited excellent recyclability without any modification as indicated by the negligible decrease in the catalytic degradation efficiency of DMP. Thus, in addition to efficient degradation of PAEs in wastewater, our study would shed light on the in-situ soil remediation technology on the basis of bisulfite-assisted heterogeneous Fenton-like reactions.

Histological characteristics of spermatogenesis stages in annual reproductive cycles of male Siberian sturgeons in various types of industrial fish farming

The modern development of aquaculture industry is inseparably associated with brood stock formation and reproduction, breeding of seeding and commercial production. Specific breeding conditions, with longer periods of water temperatures favourable for fish growth, simultaneously affect the development of the reproductive system of fish. Studies of these processes enable the best approach to obtaining reproductive products whenever the farm needs them. The study was performed at the Konakovo Division of the Branch for Freshwater Fisheries of the Federal State Budget Scientific Institution ‘Russian Federal Research Institute of Fisheries and Oceanography’ (VNIIPRKH), in a recirculating aquaculture system (RAS) and flowthrough industrial farm. Even-aged Siberian sturgeons of generation 2017 were used in the study. Samples were taken by biopsy and fixed in 70% ethanol. The paper presents the data on spermatogenesis in Siberian sturgeons in a flow-through industrial farm with annual thermal constant of 5600 degree days and with combination housing of brood fish. During the first stage, the fish are kept in a recirculating aquaculture system for 210 days, with the thermal constant of 1511 degree days, with subsequent housing and breeding in a flow-through farm for 150 days, with the thermal constant of 2340 degree days. The histological characteristics of spermatogenesis and reproductive cycles of Siberian sturgeons are presented, with a detailed description and illustrations of the processes and respective differences depending on housing conditions. The studies showed that specific temperature conditions can prolong the spawning season by 2–3 months by shifting the reproductive cycles of male Siberian sturgeons at first spawning with combination housing in flow-through tanks and RAS (prolonged wintering conditions).

Relationship between the abdominal sagging index and the reproductive performance of the Roman goose.

This research aimed to explore the changes in the observed abdominal sagging index (ASI) and reproductive performance of Roman male and female geese during the breeding period. The 339 six-month-old breeding geese (109 male; 230 female) were used in this study, in which five male and five female geese were slaughtered on a monthly basis to record the ASI. The short diameter of the testes of the male goose when the female goose lays eggs and in the second, third, and fourth months was significantly wider than in the fifth months (19.0, 20.8, 21.4, and 19.6 vs 12.7 and 14.0 mm/bird; p = 0.0105). On the other hand, the testicular weight of the male goose in the second and third months after the female goose lays eggs was significantly higher than that in the second and fifth months after laying (0.33% and 0.37% vs 0.11% and 0.19%; p = 0.0212). During the exploring period, the length and weight of the fallopian tube, the weight of the ovary, the number of follicles in 2 to 3 cm, the number of follicles in 3 to 4 cm, the fallopian tube weight in the carcass weight percentage, and the ovary weight in the carcass weight percentage all demonstrated a significant curve response. Further, female ASI was positively correlated with reproductive tract length (r = 0.815; p<0.05) and egg production per female (r = 0.790; p<0.05). The ASI classification method is more objective and easy to distinguish. This scoring method has a high correlation with the number of eggs laid by each goose and the length of the reproductive tract, inferring that the goose observation could take advantage of ASI during egg-laying and can predict the reproductive system development during the laying period and determine when the breeding goose begins to lay eggs.

Quantitation of endogenous GnRH by validated nano-HPLC-HRMS method: a pilot study on ewe plasma

Gonadotropin-releasing hormone isoform I (GnRH), a neuro-deca-peptide, plays a fundamental role in development and maintenance of the reproductive system in vertebrates. The anomalous release of GnRH is observed in reproductive disorder such as hypogonadotropic hypogonadism, polycystic ovary syndrome (PCOS), or following prenatal exposure to elevated androgen levels. Quantitation of GnRH plasma levels could help to diagnose and better understand these pathologies. Here, a validated nano-high-performance liquid chromatography–high-resolution mass spectrometry (HPLC-HRMS) method to quantify GnRH in ewe plasma samples is presented. Protein precipitation and solid-phase extraction (SPE) pre-treatment steps were required to purify and enrich GnRH and internal standard (lamprey-luteinizing hormone-releasing hormone-III, l-LHRH-III). For the validation process, a surrogate matrix approach was chosen following the International Council for Harmonisation (ICH) and FDA guidelines. Before the validation study, the validation model using the surrogate matrix was compared with those using a real matrix such as human plasma. All the tested parameters were analogous confirming the use of the surrogate matrix as a standard calibration medium. From the validation study, limit of detection (LOD) and limit of quantitation (LOQ) values of 0.008 and 0.024 ng/mL were obtained, respectively. Selectivity, accuracy, precision, recovery, and matrix effect were assessed with quality control samples in human plasma and all values were acceptable. Sixteen samples belonging to healthy and prenatal androgen (PNA) exposed ewes were collected and analyzed, and the GnRH levels ranged between 0.05 and 3.26 ng/mL. The nano-HPLC-HRMS developed here was successful in measuring GnRH, representing therefore a suitable technique to quantify GnRH in ewe plasma and to detect it in other matrices and species.Graphical abstract

Expression of CSF1, AR, and SRD5A2 during Postnatal Development of the Boar Reproductive Tract.

Simple SummaryUnderstanding the initial development of the male reproductive system, including the prostate, should provide insight into malfunctions in the adult male. Although changes in circulating androgens during development are characterized in multiple species, potential changes in the androgen receptor, in the enzyme that converts testosterone to the presumably more potent dihydrotestosterone, and in colony stimulating factor 1, a critical mediator of macrophage influence on organ development, were previously unknown and anticipated to be influenced by androgens and estrogens. Gene expression in the testis, prostate, and seminal vesicles of these three mediators of development, including responses to reduced testosterone or estrogens, were evaluated. Each of these three genes had a unique temporal pattern of expression during postnatal reproductive tract development. However, surprisingly minimal effects of altered steroid signaling were reported on the expression of these presumed pivotal genes.The male reproductive system develops from a minimally functioning gonad and nonfunctioning accessory sex glands in the neonate; sex steroids, presumed to be primary influencers of these changes, have been characterized in multiple species. This study focused on the expression of the androgen receptor as the principal mediator of androgen-induced signaling; the 5α reductase enzyme that converts testosterone to the more active dihydrotestosterone; and colony stimulating factor 1, a mediator of macrophage influence on organ development in the pig. The time points chosen to evaluate normal developmental changes during the juvenile and prepubertal intervals included the inflection time points of 6.5 weeks of age at the nadir of circulating estradiol and testosterone concentrations in juveniles, and 11 weeks of age, when these concentrations begin to increase. The role of sex steroid signaling in the regulation of gene expression was evaluated by the blockade of androgen and estrogen receptors and reduction in endogenous estrogens. Expression of colony stimulating factor 1 in the testes gradually decreased during development; developmental profiles in the prostate and seminal vesicles were clearly different. Interference with sex steroid signaling had no effect on the expression of these three genes in testicular tissue and minimal and transient effects in prostate and seminal vesicles.

Prenatal ultrasound finding of atypical genitalia: Counseling, genetic testing and outcomes.

To report uptake of genetic counseling (GC) and prenatal genetic testing after the finding of atypical genitalia on prenatal ultrasound (US) and the clinical and genetic findings of these pregnancies. A retrospective cohort study (2017-2019) of atypical fetal genitalia in a large expert center for disorders/differences of sex development. We describe counseling aspects, invasive prenatal testing, genetic and clinical outcome of fetuses apparently without [group 1, n=22 (38%)] or with [group 2, n=36 (62%)] additional anomalies on US. In group 1, 86% of parents opted for GC versus 72% in group 2, and respectively 58% and 15% of these parents refrained from invasive testing. Atypical genitalia were postnatally confirmed in 91% (group 1) and 64% (group 2), indicating a high rate of false positive US diagnosis of ambiguous genitalia. Four genetic diagnoses were established in group 1 (18%) and 10 in group 2 (28%). The total genetic diagnostic yield was 24%. No terminations of pregnancy occurred in group 1. For optimal care, referral for an expert fetal US scan, GC and invasive diagnostics including broad testing should be offered after prenatal detection of isolated atypical genitalia.

Knockdown of the Halloween Genes spook, shadow and shade Influences Oocyte Development, Egg Shape, Oviposition and Hatching in the Desert Locust.

Ecdysteroids are widely investigated for their role during the molting cascade in insects; however, they are also involved in the development of the female reproductive system. Ecdysteroids are synthesized from cholesterol, which is further converted via a series of enzymatic steps into the main molting hormone, 20-hydoxyecdysone. Most of these biosynthetic conversion steps involve the activity of cytochrome P450 (CYP) hydroxylases, which are encoded by the Halloween genes. Three of these genes, spook (spo), phantom (phm) and shade (shd), were previously characterized in the desert locust, Schistocerca gregaria. Based on recent sequencing data, we have now identified the sequences of disembodied (dib) and shadow (sad), for which we also analyzed spatiotemporal expression profiles using qRT-PCR. Furthermore, we investigated the possible role(s) of five different Halloween genes in the oogenesis process by means of RNA interference mediated knockdown experiments. Our results showed that depleting the expression of SchgrSpo, SchgrSad and SchgrShd had a significant impact on oocyte development, oviposition and hatching of the eggs. Moreover, the shape of the growing oocytes, as well as the deposited eggs, was very drastically altered by the experimental treatments. Consequently, it can be proposed that these three enzymes play an important role in oogenesis.

The Development of Normal Fetal External Genitalia Throughout Gestation.

In this review, we describe normal development of fetal genitalia throughout gestation as well as the identification of normal male and female genitalia on ultrasound. We use abnormal and ambiguous genitalia as illustrative tools to assist with the identification of normal genitalia and recognition of some of the most common abnormalities in external genitalia development.

JQ-1 ameliorates schistosomiasis liver granuloma in mice by suppressing male and female reproductive systems and egg development of Schistosoma japonicum.

Schistosomiasis is a serious and widespread parasitic disease caused by infection with Schistosoma. Because the parasite's eggs are primarily responsible for schistosomiasis dissemination and pathogenesis, inhibiting egg production is a potential approach to control the spread and severity of the disease. The bromodomain and extra-terminal (BET) proteins represent promising targets for the development of epigenetic drugs against Schistosoma. JQ-1 is a selective inhibitor of the BET protein family. In the present study, JQ-1 was applied to S. japonicum in vitro. By using laser confocal scanning microscopy and EdU incorporation assays, we showed that application of JQ-1 to worms in vitro affected egg laying and the development of both the male and female reproductive systems. JQ-1 also inhibited the expression of the reproductive-related genes SjPlk1 and SjNanos1 in S. japonicum. Mice infected with S. japonicum were treated with JQ-1 during egg granuloma formation. JQ-1 treatment significantly reduced the size of the liver granulomas and levels of serum alanine aminotransferase and aspartate aminotransferase in mice and suppressed both egg laying and the development of male and female S. japonicum reproductive systems in vivo. Moreover, the mRNA expression levels of some proinflammatory cytokines were decreased in the parasites. Our findings suggest that JQ-1 treatment attenuates S. japonicum egg-induced hepatic granuloma due at least in part to suppressing the development of the reproductive system and egg production of S. japonicum. These findings further suggest that JQ-1 or other BET inhibitors warrant additional study as a new approach for the treatment or prevention of schistosomiasis.