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Extracellular matrix abnormalities in testis and epididymis of XXSxr ("sex-reversed") mice.

Sex-reversed (Sxr) is a duplication of the sex-determining region of the Y chromosome, which gets transposed to a paternal X chromosome. Chromosomally female (XX) zygotes that receive this XSxr chromosome develop as apparent males. Previous work on XXSxr mice (called pseudomales) showed extracellular matrix (ECM) ultrastructural abnormalities in the epididymis and testis. This study examined the biochemical nature of these abnormalities. More hydroxyproline (an indicator of collagen) was noted in the pseudomale testis and epididymis compared to normal male tissues. Western blot analysis showed increased collagen IV in the pseudomale testis and epididymis. In both the hydroxyproline and collagen IV studies, the epididymis was found to contain higher levels of these substances than the testis for both genotypes. There also appeared to be increased messenger RNA for tissue inhibitor of metalloproteinases (Timp), a regulator of collagen, in the pseudomale testis. Data from these studies seem to indicate that the XXSxr genotype influences ECM deposition and/or turnover and exerts a direct genetic influence on the development of the testis and epididymis. According to the existing paradigm of mammalian sexual development, the epididymis is expected to be normal in the presence of adequate androgenization and independent of chromosomal and genetic sex. The results presented here differ from what would be predicted by this paradigm.

Animals↗

Dynamics of callose deposition and beta-1,3-glucanase expression during reproductive events in sexual and apomictic Hieracium.

Callose accumulates in the walls of cells undergoing megasporogenesis during embryo sac formation in angiosperm ovules. Deficiencies in callose deposition have been observed in apomictic plants and causal linkages between altered callose deposition and apomictic initiation proposed. In apomictic Hieracium, embryo sacs initiate by sexual and apomictic processes within an ovule, but sexual development terminates in successful apomicts. Callose deposition and the events that lead to sexual termination were examined in different Hieracium apomicts that form initials pre- and post-meiosis. In apomictic plants, callose was not detected in initial cell walls and deficiencies in callose deposition were not observed in cells undergoing megasporogenesis. Multiple initial formation pre-meiosis resulted in physical distortion of cells undergoing megasporogenesis, persistence of callose and termination of the sexual pathway. In apomictic plants, callose persistence did not correlate with altered spatial or temporal expression of a beta-1,3-glucanase gene (HpGluc) encoding a putative callose-degrading enzyme. Expression analysis indicated HpGluc might function during ovule growth and embryo sac expansion in addition to callose dissolution in sexual and apomictic plants. Initial formation pre-meiosis might therefore limit the access of HpGluc protein to callose substrate while the expansion of aposporous embryo sacs is promoted. Callose deposition and dissolution during megasporogenesis were unaffected when initials formed post-meiosis, indicating other events cause sexual termination. Apomixis in Hieracium is not caused by changes in callose distribution but by events that lead to initial cell formation. The timing of initial formation can in turn influence callose dissolution.

Cell Wall↗

The importance of folate, zinc and antioxidants in the pathogenesis and prevention of subfertility.

Current treatments of subfertile couples are usually empiric, as the true cause of subfertility often remains unknown. Therefore, we outline the role of nutritional and biochemical factors in reproduction and subfertility. A literature search was performed using MEDLINE, Science Direct and bibliographies of published work with both positive and negative results. The studies showed that folate has a role in spermatogenesis. In female reproduction, folate is also important for oocyte quality and maturation, implantation, placentation, fetal growth and organ development. Zinc has also been implicated in testicular development, sperm maturation and testosterone synthesis. In females, zinc plays a role in sexual development, ovulation and the menstrual cycle. Both folate and zinc have antioxidant properties that counteract reactive oxygen species (ROS). Thiols, such as glutathione, balance the levels of ROS produced by spermatozoa and influence DNA compaction and the stability and motility of spermatozoa. Oocyte maturation, ovulation, luteolysis and follicle atresia are also affected by ROS. After fertilization, glutathione is important for sperm nucleus decondensation and pronucleus formation. Folate, zinc, ROS and thiols affect apoptosis, which is important for sperm release, regulation of follicle atresia, degeneration of the corpus luteum and endometrial shedding. Therefore, the concentrations of these nutrients may have substantial effects on reproduction. In conclusion, nutritional and biochemical factors affect biological processes in male and female reproduction. Further research should identify pathways that may lead to improvements in care and treatment of subfertility.

Antioxidants↗

Steroid metabolism by a tumour of the specific gonadal stroma in a child.

A study of steroid metabolism by a tumour of the specific gonadal stroma was carried out in a 10 year old boy. Tumours developed in the two testes from multiple foci, and clinically, no signs of sexual development were evident. Four testicular enzymes necessary for testosterone biosynthesis were estimated in the child, in two adult controls, and in three pre-pubertal boys with male pseudohermaphroditism but normal tests of Leydig cell function. 17 alpha-Hydroxylase and 17 beta-hydroxysteroid dehydrogenase were similar in the five controls and in the gonad with the tumour, while 17,20-desmolase and 3 beta-hydroxysteroid dehydrogenase were grossly deficient in the child with the tumour. These enzyme deficiencies might explain the absence of peripheral virilization in a boy with a tumour of Leydig and Sertoli cells.

17-Hydroxysteroid Dehydrogenases↗

Crack cocaine use and sexual behavior among psychiatric inpatients.

Rises in both crack cocaine use and incidence of sexually transmitted diseases have been recently reported. In this study, we investigated the relationship between crack cocaine abuse and sexual behavior in 50 psychiatric inpatients. The relationship between crack use and sexual behavior is a very complicated one, influenced by many variables such as the dose of crack used, the user's preexisting sexuality, gender, and psychiatric illness. Results indicated that while most of the subjects developed sexual disinterest and dysfunction with prolonged crack cocaine use, some of them became more sexually promiscuous and consequently contracted more sexually transmitted diseases. The implications of these findings regarding transmission of HIV among crack cocaine users are discussed.

Adult↗

Sildenafil in the Treatment of SSRI-Induced Sexual Dysfunction: A Pilot Study.

BACKGROUND: Sexual dysfunction is a well-documented side effect of selective serotonin reuptake inhibitors (SSRIs). Commonly reported side effects include erectile impotence, anorgasmia, ejaculatory delay, pain, loss of sensation, and decreased pleasure. Early reports of the reversal of sexual dysfunction after using sildenafil in male and female patients receiving various types and dosages of SSRIs are promising and prompted this study. Our aim was to evaluate the effects of oral sildenafil on reported secondary sexual dysfunction in patients concurrently treated with SSRIs. METHOD: Fourteen male patients who developed sexual dysfunction while receiving SSRIs were screened using the Arizona Sexual Experience (ASEX) scale. An electrocardiogram was obtained at the beginning and at the end of the study. Each patient was prescribed sildenafil tablets to be taken twice a week, 25-100 mg, prior to sexual activity and told to record the findings in a running diary which he was to keep during his treatment period. The patients were seen weekly and evaluated by clinical interview and ASEX scale. Patients were treated for a total of 8 weeks. RESULTS: All but 1 of the 14 patients experienced an improvement of sexual dysfunction, with 9 patients at the first dose of 25 mg and 4 at higher doses (3 at 50 mg and 1 at 75 mg). One patient required 100 mg to obtain minimal response. DISCUSSION: Sildenafil was shown to be helpful in the treatment of SSRI-induced sexual dysfunction. Three patients continued to experience ongoing positive effects after discontinuation of sildenafil; the other 10 patients relapsed.

Journal Article↗

Deficiencies in sex-regulated expression and levels of two hepatic sterol carrier proteins in a murine model of Niemann-Pick type C disease.

Hepatic sterol carrier protein-2 (SCP2) and sterol carrier protein-X (SCPx) levels in normal and in mutant Niemann-Pick Type C mice were determined by immunoblotting with antiserum against rat SCP2. A 14-kDa protein (SCP2) was detected in the cytosol fraction and a 58-kDa protein (SCPx) was found in both cytosolic and organellar fractions. Expression of hepatic SCPx protein was developmentally regulated in a sex-specific pattern. The amounts of organelle-associated SCPx increased 4-fold during sexual development of normal males but decreased dramatically during development of normal females. Levels of hepatic SCP2 increased much less dramatically during sexual maturation of normal males and females. Adult Niemann-Pick Type C mice were deficient in both hepatic SCPx and SCP2. The deficit in SCPx in affected males reflected a failure to increase hepatic SCPx levels during sexual maturation. In affected males SCPx remained at levels found in immature mice. Affected male and female mice were also unable to maintain levels of hepatic SCP2. The level of SCP2 was near normal in affected immature males and subnormal in affected immature females. During sexual maturation hepatic SCP2 declined in affected animals.

Aging↗

tra-2 encodes a membrane protein and may mediate cell communication in the Caenorhabditis elegans sex determination pathway.

The Caenorhabditis elegans sex-determining gene, tra-2, promotes female development in XX animals. In this paper we report the cDNA sequence corresponding to a 4.7 kb tra-2 mRNA and show that it is composed of 23 exons, is trans-spliced to SL2, and contains a perfect direct repeat in the 3' untranslated region. This mRNA is predicted to encode a 1475 amino acid protein, named pTra2A, that has a secretory signal and several potential membrane-spanning domains. The molecular analysis of tra-2 loss-of-function mutations supports our open reading frame identification and suggests that the carboxy-terminal domain is important for tra-2 activity. We propose that in XX animals the carboxy-terminal domain of pTra2A negatively regulates the downstream male promoting fem genes. In XO animals, tra-2 is negatively regulated by her-1, which acts cell nonautonomously. Because hydropathy predictions suggest that pTra2A is an integral membrane protein, pTra2A might act as a receptor for the her-1 protein. We propose that in XO animals, the her-1 protein promotes male development by binding and inactivating pTra2A. The role of cell communication in C. elegans sex determination might be to ensure unified sexual development throughout the animal. If so, then regulation of sexual fate by her-1 and tra-2 might provide a general model for the coordination of groups of cells to follow a single cell fate.

Amino Acid Sequence↗

Control of mating and development in Ustilago maydis.

In Ustilago maydis the a and b mating type loci control pathogenicity as well as sexual development. We review the function of these loci in controlling the cell fusion step, the switch from yeast-like to filamentous growth and subsequent pathogenic development. Our special emphasis will be the role of pheromones and pheromone signaling in these processes.

Alleles↗

Standards for comprehensive sexual health services for young people under 25 years.

This document is a first response to the need to develop sexual health services for young people on a single site whilst awaiting research from pilot studies of 'one stop shops' suggested in the Sexual Health and HIV strategy. It is a document which is intended to be a tool to use for those wishing to set up a service providing testing for sexually transmitted infections and provision of contraceptive services for those under 25 years. It is not intended that such a service would replace existing specialist or general practice care but complement it, allowing clients to choose the service most appropriate and acceptable to them, with close links and clear pathways of care for referral between services. This paper should be used as a template when initiating and monitoring a clinic but some of the standards may not be achievable without significant financial input. However, economic limitations should not detract from striving to achieve the best possible care for those most at risk from sexually transmitted infections and unwanted pregnancies. For example, not all clinics will be able to provide the recommended tests for the diagnosis for gonorrhoea and chlamydia immediately, but should work towards achieving them. Although the upper age limit in this document is defined as 25 years, some providers may wish to limit clinics to those under 20 depending on local needs. Detailed information on specific issues such as consent and confidentiality, provision of contraception, investigation of non-sexually transmitted vaginal infections and sexually transmitted infection management and diagnosis are referenced and we recommend these are accessed by the users of this document. Many of the references themselves are live documents available on the worldwide web, and are constantly updated. The Sexual Health and HIV Strategy has now been published and these standards are aimed at those who wish to provide a level 2 sexual health service for young people wherever the setting e.g. genitourinary outreach clinic, contraceptive services, general practice. This document is a starting point to be reviewed and updated as new research becomes available, as the Sexual Health Strategy is implemented and with further input from providers of care (family planning, general practice, genitourinary medicine, gynaecology and paediatrics) and service users. All service providers must maintain a high quality of care and have networks both with those who provide more specialized services (Level 3) and Level 1 services. This document is an initial attempt to ensure that there is equity of clinical provision wherever a Level 2 sexual health service is provided and should be a useful tool for those setting up or monitoring services.

Adolescent↗

HIV-associated female sexual dysfunction - clinical experience and literature review.

Women form an increasing proportion of HIV-infected individuals in the developed world. Early data suggest that women with HIV are at particular risk of developing sexual problems. The aim of this study was to describe our anecdotal experience of HIV-infected women and to ascertain their sexual dysfunction, and also to conduct a national survey to evaluate what sexual dysfunction services are provided for women in other UK HIV centres. Retrospective analysis of clinic notes of women attending our HIV clinic and letter surveys of HIV centres in the UK were carried out. About half our cohort reported that they had sexual problems or were not satisfied with sex over the preceding 12 months. Contextual issues seemed to be the commonest cause of these problems. Sixty percent of HIV physicians in the UK rarely/never ask their female HIV patients about sexual functioning. Sexual dysfunction is probably common in HIV-infected women. Most physicians seeing women with HIV in the UK do not ask about sexual functioning. 'Physician coaching' could help to redress this situation, so that at the least the sexual problems could be brought up in discussion.

Adolescent↗

Development of feminine sexual behavior in the rat: androgenic and temporal influences.

The contributions of prenatal and postnatal androgen exposure upon the development of sexual behavior in rats were examined by prenatal treatment of pups with an androgen antagonist (flutamide) and postnatal androgenization or castration. Male and female rats were exposed to the androgen receptor-blocker flutamide (FLU) in utero via prenatal injections to the mother on Days 10 through 22 of gestation. At birth (Day 1) males were castrated. Both males and females were injected with either 100 micrograms testosterone propionate (TP) or oil on Day 1. In adulthood all gonadectomized animals were tested for the display of feminine sexual behavior (lordosis) in response to a range of estrogen dosages. Prenatal exposure to FLU enhanced lordosis in both sexes when compared to vehicle-treated controls. Postnatal TP treatment decreased lordotic potential as expected. However, in animals given TP postnatally, those receiving prenatal flutamide had higher lordosis quotients than animals receiving vehicle treatment. These data confirm (1) that the development of feminine sexual behavior is inhibited by androgen exposure, (2) that such exposure occurs prenatally, (3) that the potential for feminine behavioral differentiation occurs prenatally as well as postnatally, and (4) that androgen acts perinatally to affect estrogen sensitivity in adulthood.

Aging↗

An investigation of verbal interaction, knowledge of sexual behavior and self-concept in adolescent mothers.

Variables commonly considered to be major factors in contributing to the incidence of adolescent pregnancy may be only part of the total pattern. This study sought to examine the adolescent mothers' communication with significant others and their knowledge about sex, pregnancy, and birth control methods. Self-concepts of the adolescent mothers were compared with those of the published norms of the Tennessee Self-Concept Scale. The study included 23 adolescent mothers between the ages of 13 and 19 who were gravida 1 as indicated by their medical records. They were given a questionnaire constructed from previous research. They also completed a communication scale and the Tennessee Self-Concept Scale. The findings of the present study indicated that most adolescent mothers considered their communication with their parent mothers to be one of mutual understanding. However, it appears that most adolescent mothers obtain much of their information about sex, pregnancy, and birth control methods from significant others. The self-concepts of these adolescent mothers were lower in comparison to the norm. The results indicate a need for further research in the area of adolescent sexual development, sex education in the school, and increased involvement of parents in the communication of sexual mores.

Adolescent↗

[Menarche, orgasmic capacity and coitarche].

A group of 609 Czech 16 to 18 years old girls was divided according to the age of the first menses into three subgroups: first with menarche between 10 to 12 years, second in 13 and 14 years, third in 15 and 16 years. It was found that the age of menarche did not distinctly influence the course of their sexual development during the puberal period. The mean age of first rendezvous and coitarche did not significantly differ between the followed three subgroups. Out of the whole group of 609 probands 304 girls already had sexual intercourse. The percentage of coitally orgastic girls was highest in the subgroup with an early first menstrual bleeding between 10 and 12 years of age and the difference to the other two subgroups with a later menarche was statistically highly significant (p < 0.005). The opinion is expressed that changes in brain which enable girls to fall in love for the first time are from the point of view of biological prerequisites more important for the beginning of full sexual life in pubertal girls than hormonal development manifested by first menstrual bleeding.

Adolescent↗

Embryonic testicular regression. A clinical spectrum of XY agonadal individuals.

Aberrations of fetal sexual development were studied in three XY agonadal individuals. Two were phenotypic females with primary amenorrhea, sexual infantilism, and no internal genital structures. Plasma androstenedione and testosterone concentrations were similar to those of prepubertal children and increased after ACTH infusion. The daily production rates of estrone were low. The third agonadal XY individual, a phenotypic male, developed gynecomastia in response to approximately 40 mug of estrone produced daily by the extraglandular aromatization of plasma androstenedione. All plasma testosterone was accounted for by the conversion of plasma androstenedione. The absence of internal genitalia, the prepubertal external genitalia in the phenotypic females, and the incomplete growth of both the internal and external genital structures in the phenotypic male subject suggest that testicular elaboration of müllerian regression substance occurred, but that regression of the testes occurred subsequently during varying stages of embryogenesis. In the females, testicular regression occurred prior to the initiation of fetal testicular production of androgen. On the other hand, in the male subject, testicular activity persisted longer; thus, both müllerian duct regression and embryonic virilization of wolffian ducts and genital tubercles occurred.

Adolescent↗

On the possible prevention of sexual problems in adolescence.

The author contends that a primary cause of sexual problems is failure to teach children about sex before they reach adolescence. Physical and mental growth are nurtured and supported throughout infancy and childhood, while sexual development is stifled or distorted. As a result children reach adolescence with their natural eroticism maimed. The author pleads for a basic change in the attitudes of adults, so that parents will begin to teach their children about sexuality. By adolescence children should be prepared to understand and accept their capacity for sexual expression and be fully aware of when and how it might or might not be appropriate.

Adolescent↗

Role of gonadal hormones in development of the sexual phenotypes.

Male and female embryos develop in an identical fashion during the initial portion of gestation. If the indifferent gonad differentiates into an ovary (or if no gonad is present), a female phenotype is formed. Male phenotypic differentiation, however, requires the presence of an endocrinologically active testis. Two secretions of the fetal testis, Müllerian inhibiting substance and testosterone, are responsible for male development. Studies of single gene mutations that interfere with androgen action indicate that testosterone itself is responsible for virilization of the Wolffian duct system into the epididymis, vas deferens, and seminal vesicle, whereas the testosterone metabolite dihydrotestosterone induces development of the prostate and male external genitalia. Thus, impairment of dihydrotestosterone formation results in a characteristics phenotype consisting of predominantly female external genitalia but normally virilized Wolffian ducts. The molecular mechanisms by which testosterone and dihydrotestosterone act during fetal development appear to involve the same high affinity receptor, a protein that transports both testosterone and dihydrotestosterone to the nucleus of target cells. When this receptor is either absent, deficient, or structurally abnormal, the actions of both testosterone and dihydrotestosterone are impaired, and the resulting developmental anomalies involve both internal and external genital structures.

Anti-Mullerian Hormone↗

Targeting the adolescent male.

The National Urban League regards too early parenting among adolescents as an issue requiring high level, active attention from all segments of the Black community. Poverty, single parent households and adolescent pregnancies are not exclusively female problems. The role that males play has been missing from too many studies of these phenomena. In light of the fact that most sexual activity is male initiated, and most sexual behavior is male influenced, it becomes clear that there will be no resolution of the problem of teenage pregnancy without directing greater attention to the male. The issue of male responsibility is skirted too often due to parental pride on the part of mothers and fathers when their male children seek sexual relations with female partners. It is viewed as a sign that they are developing sexually within the norm. This is especially true, in many instances, in female headed households where the mother is concerned that she may not be providing her son with an adequate male role model. Sexual activity by female adolescents, however, is generally not condoned. This confusing double standard is further compounded by the disjointed fashion in which American society responds to adolescent sexuality on the whole. Although the home should be the focal point, many parents reluctantly admit an inability to communicate effectively about sex with their pre-adolescent children. Thus, the school, church, community and social agencies have all been enlisted in this task. The National Urban League's initiative in this area is expected to have significant impact on the course of adolescent sexuality and reproductive responsibility.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗