Development Of Male Reproductive Organs Research Articles

Galaxolide and Irgacure 369 are novel environmental androgens

Endocrine disruptors are environmental chemicals that can interfere with the endocrine system. However, research on endocrine disruptors that interfere with androgen's actions is still limited. The purpose of this study is to use in silico computation, i.e., molecular docking to facilitate the identification of environmental androgens. Computational docking was used to study the binding interactions of environmental/industrial compounds with the three dimensional structure of human androgen receptor (AR). Then reporter assay and cell proliferation assay using AR-expressing LNCaP prostate cancer cells were used to determine their in vitro androgenic activity. Animal studies using immature male rats were also carried out to test their in vivo androgenic activity. Two novel environmental androgens were identified. As a photoinitiator, 2-benzyl-2-(dimethylamino)-4′-morpholinobutyrophenone (Irgacure 369, abbreviated as IC-369) is widely used in the packaging and electronics industries. Galaxolide (HHCB) is widely used in the production of perfume, fabric softeners and detergents. We found that both IC-369 and HHCB could activate AR transcriptional activity and promote cell proliferation in AR-sensitive LNCaP cells. Furthermore, IC-369 and HHCB could induce cell proliferation and histological changes of seminal vesicles in immature rats. RNA sequencing and qPCR analysis showed that androgen-related genes in seminal vesicle tissue were up-regulated by IC-369 and HHCB. In conclusion, IC-369 and HHCB are new environmental androgens that bind AR and induce AR transcriptional activity, thereby exerting toxicological effects on the development of male reproductive organs.

Intronic Enhancer Is Essential for Nr5a1 Expression in the Pituitary Gonadotrope and for Postnatal Development of Male Reproductive Organs in a Mouse Model.

Nuclear receptor subfamily 5 group A member 1 (NR5A1) is expressed in the pituitary gonadotrope and regulates their differentiation. Although several regulatory regions were implicated in Nr5a1 gene expression in the pituitary gland, none of these regions have been verified using mouse models. Furthermore, the molecular functions of NR5A1 in the pituitary gonadotrope have not been fully elucidated. In the present study, we generated mice lacking the pituitary enhancer located in the 6th intron of the Nr5a1 gene. These mice showed pituitary gland-specific disappearance of NR5A1, confirming the functional importance of the enhancer. Enhancer-deleted male mice demonstrated no defects at fetal stages. Meanwhile, androgen production decreased markedly in adult, and postnatal development of reproductive organs, such as the seminal vesicle, prostate, and penis was severely impaired. We further performed transcriptomic analyses of the whole pituitary gland of the enhancer-deleted mice and controls, as well as gonadotropes isolated from Ad4BP-BAC-EGFP mice. These analyses identified several genes showing gonadotrope-specific, NR5A1-dependent expressions, such as Spp1, Tgfbr3l, Grem1, and Nr0b2. These factors are thought to function downstream of NR5A1 and play important roles in reproductive organ development through regulation of pituitary gonadotrope functions.

Exploration and utilization of maize male sterility resources.

Male sterility refers to the defective development of male reproductive organs, which led to plants incapable of producing normal and functional pollens. Maize (Zea mays L.) is one of the most important food crops, as well as one of the earliest crops to utilize heterosis in breeding. Single cross hybrid has been the main type of maize heterosis utilization for a long time. The planting area of maize hybrid in China has been stable at about 620 million mu. More than one billion kilograms of commercial hybrid seeds are needed each year, and the annual seed production area has been stable at about 2.5 million mu in recent years. So far, manual emasculation has been the major way of maize hybrid seed production in China, which is laborious and time consuming. Generally, spatial isolation is necessary for maize hybrid seed production, this requirement results in only some regions in the country suitable for maize hybrid seed production. Manual emasculation requires seasonal demand of labors. At present, with the urbanization of a large number of rural laborers, the seed production regions experience a serious labor shortage. Accordingly, the cost of seed production increases with the rising of land rent and labor costs. In addition, it is difficult to guarantee the seed purity with manual or mechanical emasculation for hybrid seed production. However, incorporating male sterility into maize hybrid seed production could reduce its cost and ensure hybrid seed purity. It can also avoid the difficulties of manual or mechanical emasculation in field operation under extreme weather conditions. Therefore, it is the inevitable trend of development in the maize seed industry. In this review, we summarize the exploitation and creation of maize cytoplasmic male sterility (CMS), maize genic male sterility (GMS) resources in China, and the developing process from natural discovery to targeted creation of male sterility resources in plants, and the research progress of maize male sterility. We then analyze the application status and existing problems of maize male sterility, based on the development trend of maize seed industry, as well as the research and application status of male sterility in China. We also identify seven aspects that need to be further strengthen, thereby providing the reference for the creation, research and utilization of maize male sterility in the future.

Effect of Bisphenol A on the Testis of Offspring of White Albino Rats during Pregnancy and Lactation: (Light and Electron Microscopic Study)

Introduction: The synthetic industrial and biomedical chemicals suspected to threat the health of the living organisms by disrupting their endocrine systems, referred to as endocrine disrupting chemicals (EDCs). Objective: To study the effects of Bisphenol A (BPA) on the natal and postnatal testis by the light and electron microscope to make sure if it is harmful or not on the development of male reproductive organs in albino rats. Matrial and Methods: Chemical used: Bisphenol A. The daily single oral dose was (0.3 mg/kg BW./day). Experimental animals: Adult female rats in proestrus cycle were caged overnight with adult males of proven fertility (1 male / 2 females / cage) and produced neonatal male rats.The offspring rats were divided into five main groups: Group I (Control offspring group), Group II (Experimental low dose treated offspring group with Bisphenol A (0.3 mg/kg BW./day) for two weeks, Group III (Experimental high dose treated offspring group; 12 mg/kg b.w/day), Group IV (First recovery group ), Group V (Second recovery group), Results: Chronic Bisphenol A administration produced testicular toxicity leading to marked serious histological changes of the testis including the spermatogenic cells, spermatids, Sertoli cells and Leydig cells. These testicular changes increased with the high dose intake of BPA indicating its cumulative toxic effects that caused hypospermatogenesis, leading to infertility. Conclusion: Bisphenol A administration causes testicular toxicity. So, these serious complications on testicular structure should be considered when buying any canned foods or drinks, because it is used nowadays on a large scale allover the world.

Iprodione and chlorpyrifos induce testicular damage, oxidative stress, apoptosis and suppression of steroidogenic- and spermatogenic-related genes in immature male albino rats.

The fungicide iprodione (IPR) and the insecticide chlorpyrifos (CPF) are concurrently applied for early disease control in fruits and other crops. However, there are no available data about the impacts of their co-exposure. Additionally, IPR and CPF are known as endocrine disruptors that can cause reproductive toxicity. The outcomes of their co-exposure on the development of male reproductive organs are still unknown. Therefore, this study aimed to assess the risk of exposure to these pesticides, particularly on the postnatal development of the male albino rat reproductive system from postnatal days 23-60. The results revealed that a single IPR or CPF exposure has harmful consequences on the reproductive development and function manifested by reduced testicular weight, serious changes in sperm characteristics, reproductive hormone level imbalance, testicular enzymes, oxidative stress and apoptosis-related enzymes, which correlated with transcription levels of steroidogenic- and spermatogenic-related genes. Histopathologically, both compounds caused severe damage in the testis and accessory glands architecture. Notably, co-exposure to IPR and CPF in rats caused more serious damage, indicative of an additive effect than individual exposure, so concurrent exposure should be avoided as it is more hazardous, especially on male fertility.

SAP130 and CSN1 interact and regulate male gametogenesis in Arabidopsis thaliana.

COP9 signalosome (CSN) is a nuclear complex composed of eight distinct subunits that governs vast developmental processes in Arabidopsis thaliana (L.) Heynh. The null alleles of csn mutants display pleiotropic phenotypes that result in seedling lethality. To date, several partially complemented transgenic plants, expressing the particular CSN subunit in its corresponding null mutant allele, were utilized to bypass seedling lethality and investigate CSN regulation at later stages of development. One such transgenic plant corresponding to CSN1 subunit, fus6/CSN1-3-4, accumulates wild-type level of CSN1 and displays normal plant architecture at vegetative stage. Here we show through histological analyses that fus6/CSN1-3-4 plants display impairment of pollen development at the bicellular stage. This defect is identical to that observed in RNAi plants of SAP130, encoding a subunit of the multiprotein splicing factor SF3b. We further dissected the previously reported interaction between CSN1 and SAP130, to reveal that approximately 100 amino-acid residues located at the N-terminal end of CSN1 (CSN1NN) were essential for this interaction. In silico structure modeling demonstrated that CSN1NN could swing out towards SAP130 to dock onto its Helical Insertion protruding from the structure. These results support our model that CSN1 embeds itself within CSN protein complex through its C-terminal half and reaches out to targets through its N-terminal portion of the protein. Taken together, this is the first report to document the identical loss-of-function phenotypes of CSN1 and SAP130 during male gametogenesis. Thus, we propose that SAP130 and CSN1 coordinately regulate development of male reproductive organs.

Nandrolone Decanoate: Use, Abuse and Side Effects.

Background and Objectives: Androgens play a significant role in the development of male reproductive organs. The clinical use of synthetic testosterone derivatives, such as nandrolone, is focused on maximizing the anabolic effects and minimizing the androgenic ones. Class II anabolic androgenic steroids (AAS), including nandrolone, are rapidly becoming a widespread group of drugs used both clinically and illicitly. The illicit use of AAS is diffused among adolescent and bodybuilders because of their anabolic proprieties and their capacity to increase tolerance to exercise. This systematic review aims to focus on side effects related to illicit AAS abuse, evaluating the scientific literature in order to underline the most frequent side effects on AAS abusers’ bodies. Materials and Methods: A systematic review of the scientific literature was performed using the PubMed database and the keywords “nandrolone decanoate”. The inclusion criteria for articles or abstracts were English language and the presence of the following words: “abuse” or “adverse effects”. After applying the exclusion and inclusion criteria, from a total of 766 articles, only 148 were considered eligible for the study. Results: The most reported adverse effects (found in more than 5% of the studies) were endocrine effects (18 studies, 42%), such as virilization, gynecomastia, hormonal disorders, dyslipidemia, genital alterations, and infertility; cardiovascular dysfunctions (six studies, 14%) such as vascular damage, coagulation disorders, and arteriosus hypertension; skin disorders (five studies, 12%) such as pricking, acne, and skin spots; psychiatric and mood disorders (four studies, 9%) such as aggressiveness, sleep disorders and anxiety; musculoskeletal disorders (two studies, 5%), excretory disorders (two studies, 5%), and gastrointestinal disorders (two studies, 5%). Conclusions: Based on the result of our study, the most common adverse effects secondary to the abuse of nandrolone decanoate (ND) involve the endocrine, cardiovascular, skin, and psychiatric systems. These data could prove useful to healthcare professionals in both sports and clinical settings.

Molecular characterization of XX maleness

Androgens and anti-Mullerian hormone (AMH), secreted by the foetal testis, are responsible for the development of male reproductive organs and the regression of female anlagen. Virilization of the reproductive tract in association with the absence of Mullerian derivatives in the XX foetus implies the existence of testicular tissue, which can occur in the presence or absence of SRY. Recent advancement in the knowledge of the opposing gene cascades driving to the differentiation of the gonadal ridge into testes or ovaries during early foetal development has provided insight into the molecular explanation of XX maleness.

Molecular Characterization of XX Maleness.

Androgens and anti-Müllerian hormone (AMH), secreted by the foetal testis, are responsible for the development of male reproductive organs and the regression of female anlagen. Virilization of the reproductive tract in association with the absence of Müllerian derivatives in the XX foetus implies the existence of testicular tissue, which can occur in the presence or absence of SRY. Recent advancement in the knowledge of the opposing gene cascades driving to the differentiation of the gonadal ridge into testes or ovaries during early foetal development has provided insight into the molecular explanation of XX maleness.

Glyphosate-based herbicide exposure during pregnancy and lactation malprograms the male reproductive morphofunction in F1 offspring.

One of the most consumed pesticides in the world is glyphosate, the active ingredient in the herbicide ROUNDUP®. Studies demonstrate that glyphosate can act as an endocrine disruptor and that exposure to this substance at critical periods in the developmental period may program the fetus to induce reproductive damage in adulthood. Our hypothesis is that maternal exposure to glyphosate during pregnancy and lactation in mice will affect the development of male reproductive organs, impairing male fertility during adult life. Female mice consumed 0.5% glyphosate-ROUNDUP® in their drinking water [glyphosate-based herbicide (GBH) group] or filtered water [control (CTRL) group] from the fourth day of pregnancy until the end of the lactation period. Male F1 offspring were designated, according to their mother's treatment, as CTRL-F1 and GBH-F1. Female mice that drank glyphosate displayed reduced body weight (BW) gain during gestation, but no alterations in litter size. Although GBH male F1 offspring did not exhibit modifications in BW, they demonstrated delayed testicular descent. Furthermore, at PND150, GBH-F1 mice presented a lower number of spermatozoa in the cauda epididymis and reduced epithelial height of the seminiferous epithelium. Notably, intratesticular testosterone concentrations were enhanced in GBH-F1 mice; we show that it is an effect associated with increased plasma and pituitary concentrations of luteinizing hormone. Therefore, data indicate that maternal exposure to glyphosate-ROUNDUP® during pregnancy and lactation may lead to decreased spermatogenesis and disruptions in hypothalamus-pituitary-testicular axis regulation in F1 offspring.

TIA1 is a gender-specific disease modifier of a mild mouse model of spinal muscular atrophy

Spinal muscular atrophy (SMA) is caused by deletions or mutations of Survival Motor Neuron 1 (SMN1) gene. The nearly identical SMN2 cannot compensate for SMN1 loss due to exon 7 skipping. The allele C (C+/+) mouse recapitulates a mild SMA-like phenotype and offers an ideal system to monitor the role of disease-modifying factors over a long time. T-cell-restricted intracellular antigen 1 (TIA1) regulates SMN exon 7 splicing. TIA1 is reported to be downregulated in obese patients, although it is not known if the effect is gender-specific. We show that female Tia1-knockout (Tia1−/−) mice gain significant body weight (BW) during early postnatal development. We next examined the effect of Tia1 deletion in novel C+/+/Tia1−/− mice. Underscoring the opposing effects of Tia1 deletion and low SMN level on BW gain, both C+/+ and C+/+/Tia1−/− females showed similar BW gain trajectory at all time points during our study. We observed early tail necrosis in C+/+/Tia1−/− females but not in males. We show enhanced impairment of male reproductive organ development and exacerbation of the C+/+/Tia1−/− testis transcriptome. Our findings implicate a protein factor as a gender-specific modifier of a mild mouse model of SMA.

Histological Development of Male Reproductive Organs in Microminipigs.

Microminipigs are becoming increasingly attractive alternatives for various experimental applications, such as general toxicology studies, owing to their manageable size. However, there are limited studies on the male reproductive organs of microminipigs, particularly on the histological aspects of sexual maturity. To clarify the development of male reproductive organs, 35 male microminipigs, aged 0 to 12 months, were used in this study. Histological and histomorphological evaluation was performed based on spermatogenic development, measurement of tubular structure in testes and epididymides, and histological progress of accessory glands. In addition, spontaneous testicular changes were quantitatively assessed. Histologically, male microminipigs sexually matured around 4.5 months of age, when spermatogenesis in testes and structural development in genital organs were completed. Spontaneous testicular changes occurred in all the animals investigated. Multinucleated giant cell was most commonly observed, followed by hypospermatogenesis and tubular atrophy/hypoplasia. However, the number of affected tubules was less than 1% in testes after 4.5 months of age, suggesting that the influence of these changes on evaluation of toxicity studies may be minimal. It is preferable to use sexually mature animals in toxicology studies; therefore, the information obtained by the present study will be helpful for future toxicity evaluations in microminipigs.

Myclobutanil worsens nonalcoholic fatty liver disease: An in vitro study of toxicity and apoptosis on HepG2 cells

Myclobutanil is a conazole class fungicide widely used as an agrichemical. It is approved for use on fruit, vegetables and seed commodities in the EU and elsewhere to control fungi such as Ascomycetes, Fungi Imperfecti and, Basidiomycetes. Its widespread use has raised the issue of possible health risks for agrarian communities and the general population, which can be exposed to residues present in food and drinking water. The toxicities identified include adverse effects on liver and kidney and on the development of male reproductive organs. Since the liver is the first-line organ in the defense against xenobiotics, toxic effects on hepatic metabolism cause degeneration, necrosis, and tissue hypertrophy. Therefore, we investigated myclobutanil’s effects on the human liver cell line HepG2. We found that myclobutanil increases the amount of fatty acids in these hepatic cells, as evaluated with Oil Red O staining, and progressively reduces cell viability from 1ppm to 500ppm. Analysis of biomarkers such as Bcl-xL/Bak and Mcl-1/Bak confirmed activation of cell death pathways at low doses. Therefore, myclobutanil may play an important role in the pathogenesis and progression of chronic hepatocellular diseases in humans.

Severe impairment of male reproductive organ development in a low SMN expressing mouse model of spinal muscular atrophy

Spinal muscular atrophy (SMA) is caused by low levels of survival motor neuron (SMN), a multifunctional protein essential for higher eukaryotes. While SMN is one of the most scrutinized proteins associated with neurodegeneration, its gender-specific role in vertebrates remains unknown. We utilized a mild SMA model (C/C model) to examine the impact of low SMN on growth and development of mammalian sex organs. We show impaired testis development, degenerated seminiferous tubules, reduced sperm count and low fertility in C/C males, but no overt sex organ phenotype in C/C females. Underscoring an increased requirement for SMN expression, wild type testis showed extremely high levels of SMN protein compared to other tissues. Our results revealed severe perturbations in pathways critical to C/C male reproductive organ development and function, including steroid biosynthesis, apoptosis, and spermatogenesis. Consistent with enhanced apoptosis in seminiferous tubules of C/C testes, we recorded a drastic increase in cells with DNA fragmentation. SMN was expressed at high levels in adult C/C testis due to an adult-specific splicing switch, but could not compensate for low levels during early testicular development. Our findings uncover novel hallmarks of SMA disease progression and link SMN to general male infertility.

Environmental endocrine disruptors: Effects on the human male reproductive system.

Incidences of altered development and neoplasia of male reproductive organs have increased during the last 50 years, as shown by epidemiological data. These data are associated with the increased presence of environmental chemicals, specifically "endocrine disruptors," that interfere with normal hormonal action. Much research has gone into testing the effects of specific endocrine disrupting chemicals (EDCs) on the development of male reproductive organs and endocrine-related cancers in both in vitro and in vivo models. Efforts have been made to bridge the accruing laboratory findings with the epidemiological data to draw conclusions regarding the relationship between EDCs, altered development and carcinogenesis. The ability of EDCs to predispose target fetal and adult tissues to neoplastic transformation is best explained under the framework of the tissue organization field theory of carcinogenesis (TOFT), which posits that carcinogenesis is development gone awry. Here, we focus on the available evidence, from both empirical and epidemiological studies, regarding the effects of EDCs on male reproductive development and carcinogenesis of endocrine target tissues. We also critique current research methodology utilized in the investigation of EDCs effects and outline what could possibly be done to address these obstacles moving forward.

Impact of maternal hyperlipidic hypercholesterolaemic diet on male reproductive organs and testosterone concentration in rabbits.

The concept of Developmental Origins of Health and Disease initially stemmed from the developmental programming of metabolic diseases. Reproductive functions and fertility in adulthood may also be programmed during foetal development. We studied the impact of dietary-induced maternal hyperlipidaemia and hypercholesterolaemia (HH), administered at 10 weeks of age and throughout the gestation and lactation, on male reproductive functions of rabbit offspring. Male rabbits born to HH dams and fed a control diet had significantly lighter testes and epididymes compared with rabbits born to control dams at adulthood. No significant changes in sperm concentration, sperm DNA integrity and sperm membrane composition were observed, but serum-free testosterone concentrations were decreased in HH males. This study confirms the importance of maternal metabolic status for the development of male reproductive organs.

Effect of Sialoadenectomy on the development of male reproductive organs in mice (Mus musculus).

Submandibular gland is rich source of epidermal growth factor (EGF). To investigate the role of salivary EGF on the development of male reproductive system we have performed the sialoadenectomy (removal of submandibular glands) of the 20 days old male mice and this sialoadenectomised mice was sacrificed on 45, 60 and 90th day. The testis, seminal vesicle, prostate gland, caput and cauda epididymis were dissected out for protein estimation and histological studies. It was found that the there was significant loss in the weight of these organs, protein content in the sialoadenectomised mice as compared to control. The histological structures of these organs were also changed in the sialoadenectomised mice. Keyword: Sialoadenectomy, Histology, weight, Protein

Adaptor Protein Complex 2–Mediated Endocytosis Is Crucial for Male Reproductive Organ Development in Arabidopsis

Fertilization in flowering plants requires the temporal and spatial coordination of many developmental processes, including pollen production, anther dehiscence, ovule production, and pollen tube elongation. However, it remains elusive as to how this coordination occurs during reproduction. Here, we present evidence that endocytosis, involving heterotetrameric adaptor protein complex 2 (AP-2), plays a crucial role in fertilization. An Arabidopsis thaliana mutant ap2m displays multiple defects in pollen production and viability, as well as elongation of staminal filaments and pollen tubes, all of which are pivotal processes needed for fertilization. Of these abnormalities, the defects in elongation of staminal filaments and pollen tubes were partially rescued by exogenous auxin. Moreover, DR5rev:GFP (for green fluorescent protein) expression was greatly reduced in filaments and anthers in ap2m mutant plants. At the cellular level, ap2m mutants displayed defects in both endocytosis of N-(3-triethylammonium-propyl)-4-(4-diethylaminophenylhexatrienyl) pyridinium dibromide, a lypophilic dye used as an endocytosis marker, and polar localization of auxin-efflux carrier PIN FORMED2 (PIN2) in the stamen filaments. Moreover, these defects were phenocopied by treatment with Tyrphostin A23, an inhibitor of endocytosis. Based on these results, we propose that AP-2-dependent endocytosis plays a crucial role in coordinating the multiple developmental aspects of male reproductive organs by modulating cellular auxin level through the regulation of the amount and polarity of PINs.

Genetic and environmental contributions to saliva testosterone levels in male and female infant twins

Testosterone is the key hormone for the development of male reproductive organs and secondary sexual characteristics. In addition, testosterone is associated with behavioural traits, including sexual behaviour and social dominance. The level of circulating testosterone in the human body is determined by genetic and environmental factors. Twin studies have shown moderate to high heritability in adolescence and adulthood, but heritability in early childhood has not been investigated. This study aimed at disentangling the genetic and environmental contributions to testosterone levels soon after birth. Using a sample of 314 twin pairs, saliva testosterone levels were measured at 5 months after birth. Quantitative genetic modelling was used to assess genetic and environmental contributions to the variation in testosterone levels. Variation in testosterone levels was explained by common (56.6%) and unique (43.4%) environmental factors. Taken together, these data from the largest study of twin testosterone levels suggest that, in contrast to findings in adulthood, environmental factors determine the interindividual variability in testosterone levels in early infancy. This may have consequences for the development of sex-related behaviour during childhood and calls for studies designed to unravel specific genetic and environmental factors involved in this process.

High temperature induced fertility transition and anther carbohydrate metabolism modification in a canola recessive genic male sterile line

High temperature stress is an important abiotic stress during plant growth and development that can damage canola male reproductive organ development. In this present study, we characterized a canola genic male sterile line that its fertility can be restored after high temperature induction with heterozygous but not homozygous condition. Anther length and weight was elongated and increased 2 and 5.7 times at 9 days after high temperature treatment in heterozygous line. Furthermore, viable pollen grain was produced in the anther. Anther carbohydrate content was assayed. The result showed that fructose and sucrose contents were much more stable under heat stress both in hetero- or homozygous lines. However, glucose and starch content was considerably increased after high temperature treatment in heterozygous line. In particular, anther glucose content was twice as much as that of starch content after 5 days high temperature treatment. Activity of neutral invertase, acid invertase, and sucrose synthase were increased in the anther of heterozygous line under heat stress. But activity of neutral invertase was the highest among these three sucrose cleavage enzymes. Both activity of sucrose phosphate synthase and starch phosphorylase were decreased under heat stress in the anther of heterozygous line. Activity of ADP glucose pyrophosphorylase was greatly increased in the heterozygous line, which was beneficial for starch accumulation. Transcription level of carbohydrate related genes was analyzed. 27 and 34 of the carbohydrate related genes were identified for down- and up-regulated in the anther of heterozygous line, respectively. Their function involved in the regulation of heat tolerance of heterozygous line was also discussed. Key words: Canola, carbohydrate, gene.