Sex Bias in Asthma Prevalence and Pathogenesis.

Sex-related differences in asthma prevalence are well established and change through the reproductive phases of life. As children, boys have increased prevalence of asthma compared to girls. However, as adults, women have increased prevalence of asthma compared to men. Many factors, including genetics, environment, immunological responses, and sex hormones, affect the sex disparity associated with the development and control of asthma and other allergic diseases. Fluctuations of hormones during puberty, menstruation, pregnancy, and menopause, alter asthma symptoms and severity. In this article, we review clinical and epidemiological studies that examined the sex disparity in asthma and other allergic diseases as well as the role of sex hormones on asthma pathogenesis.

The role of female hormonal factors in the development of rheumatoid arthritis.

RA is the most common chronic systemic autoimmune disease, with a higher prevalence in women, suggesting female hormonal factors play a role in the development of the disease. However, many controversies still exist. The aim of this review was to appraise data from recent research concerning female hormonal factors and their association with RA disease development. The study of female hormonal factors is challenging because serum levels may differ throughout a woman's lifetime and interact with various environmental, immunological, genetic and endocrine factors influencing the development of autoimmunity. As some female hormonal factors may be potentially modifiable, understanding their impact on RA development is clinically relevant and may result in specific preventive interventions in high-risk populations.

Immunologic challenges of human reproduction: an evolving story.

Characterization of the implanting human fetus as an allograft prompted a field of research in reproductive immunology that continues to fascinate and perplex scientists. Paternal- or partner-derived alloantigens are present in the maternal host at multiple times during the reproductive process. They begin with exposure to semen, continue through implantation and placentation, and may persist for decades in the form of fetal microchimerism. Changes in maternal immune responses that allow allogenic fertilization and survival of semiallogenic concepti to delivery must be balanced with a continued need to respond appropriately to pathogenic invaders, commensals, cell or tissue damage, and any tendency toward malignant transformation. This complex and sophisticated balancing act is essential for survival of mother, fetus, and the species itself. We will discuss concepts of alloimmune recognition, tolerance, and ignorance as they pertain to mammalian reproduction with a focus on human reproduction, maternal immune modulation, and the very earliest events in the reproductive process, fertilization and implantation.

Fertility defects in Surfactant associated protein D knockout female mice: altered ovarian hormone profile.

Surfactant associated protein D (SFTPD, also known as SP-D), a pattern recognition molecule, is an integral component of the mucosal immune system of female reproductive tract (FRT). In addition to host defense functions in the FRT, recent evidences indicate immunomodulatory role of SFTPD in parturition and pre-term labor. Regulation of SFTPD expression by ovarian hormones in the mouse uterus implicates SFTPD of FRT in pregnancy establishment and maintenance. In the current study, we attempted to decipher the functional relevance of SFTPD in FRT by characterizing the fertility parameters of surfactant associated protein D knockout (Sftpd(tm1Jhf)/Sftpd(tm1Jhf)) female mice. Knockout female mice exhibited extended estrous cycle with altered serum profile of ovarian hormones. We also demonstrate altered expression of ovarian hormone receptors and hormone responsive genes ITGB1, LIF and HOXA10 in uteri of these mice. Knockout females mated with wild type males had significantly smaller litter size due to increased pre-implantation embryo loss. We also observed an altered immune profile in knockout mice uteri with elevated levels of inflammatory cytokines, increased numbers of pro-inflammatory monocytes/macrophages and lower FOXP3 levels during the pre-implantation period. LPS administration to pregnant knockout mice did not result in any increase in embryo implantation loss and was associated with a blunted uterine pro-inflammatory response, plausibly due to higher levels of serum progesterone. Taken together, our results demonstrate that SFTPD deficiency affects female fertility, highlighting roles for SFTPD in ovarian and uterine physiology.

Bilateral eyestalk ablation of the blue swimmer crab, Portunus pelagicus, produces hypertrophy of the androgenic gland and an increase of cells producing insulin-like androgenic gland hormone.

The androgenic glands (AG) of male decapod crustaceans produce insulin-like androgenic gland (IAG) hormone that controls male sex differentiation, growth and behavior. Functions of the AG are inhibited by gonad-inhibiting hormone originating from X-organ-sinus gland complex in the eyestalk. The AG, and its interaction with the eyestalk, had not been studied in the blue swimmer crab, Portunus pelagicus, so we investigated the AG structure, and then changes of the AG and IAG-producing cells following eyestalk ablation. The AG of P. pelagicus is a small endrocrine organ ensheathed in a connective tissue and attached to the distal part of spermatic duct and ejaculatory bulb. The gland is composed of several lobules, each containing two major cell types. Type I cells are located near the periphery of each lobule, and distinguished as small globular cells of 5-7 µm in diameter, with nuclei containing mostly heterochromatin. Type II cells are 13-15 µm in diameter, with nuclei containing mostly euchromatin and prominent nucleoli. Both cell types were immunoreactive with anti-IAG. Following bilateral eyestalk ablation, the AG underwent hypertrophy, and at day 8 had increased approximately 3-fold in size. The percentage of type I cells had increased more than twice compared with controls, while type II cells showed a corresponding decrease.

Role of ovarian hormones in age-associated thymic involution revisited.

A commonly held view that ovarian hormones are causally involved in age-associated thymic involution has been recently challenged. In particular, their relevance in the progression of thymic involution has been disputed. To reassess this issue 10-month-old rats with well advanced thymic involutive changes were ovariectomized (Ovx), and after 1 month thymic cellularity, thymocyte development and levels of recent thymic emigrants (RTEs) were examined in peripheral blood and spleen. In addition, the distribution of major conventional and regulatory T-cell subsets was analyzed in the same peripheral lymphocyte compartments. Ovariectomy increased thymic weight and cellularity above the levels in both 10-month-old and age-matched controls indicating that ovarian hormone ablation not only prevented further progression of thymic involution, but also reversed it. The increased thymic cellularity was accompanied by altered thymocyte differentiation/maturation culminating in increased thymic output of naïve T cells as indicated by elevated levels of both CD4+ and CD8+ RTEs in peripheral blood and spleen. The changes in T-cell development produced: (i) a disproportional increase in cellularity across thymocyte subsets, so that relative proportions of cells at all maturational stages preceding the CD4+CD8+ T cell receptor (TCR)alphabeta(low) stage were reduced; the relative numbers of CD4+CD8+ TCRalphabeta(low) cells entering positive selection and their immediate CD4+CD8+ TCRalphabeta(high) descendents were increased, while those of the most mature CD4+CD8- and CD4-CD8+ TCRalphabeta(high) cells remained unaltered; (ii) enhanced cell proliferation across all thymocyte subsets and (iii) reduced apoptosis of cells within the CD4+CD8+ thymocyte subset. The augmented thymic output of naïve T cells in Ovx rats most likely reflected an early disinhibition of thymocyte development followed by increased positive/reduced negative selection, at least partly, due to raised thymocyte surface Thy-1 expression. The greater number of CD4+CD25+Foxp3+ cells in both thymus and peripheral blood suggested augmented thymic production of these cells. In addition, an increased CD4+/CD8+ cell ratio was found in the spleen of Ovx rats. Thus, ovarian hormone ablation led not only to increased diversity of the T-cell repertoire, but also to a new balance among distinct T-cell subsets in the periphery.

Self-regulation and women with asthma.

PURPOSE OF REVIEW: Recent research related to sex and gender role influences on asthma in women is summarized. Implications for enhancing women's self-regulation and ability to manage asthma effectively are discussed. RECENT FINDINGS: Studies in the past year have indicated that asthma is a significant burden on women and emphasized the importance of control, especially during pregnancy. The significance of hormonal variation in symptoms and severity has been noted. An association between weight and asthma has been observed. Evidence suggests that hormonal changes contribute to the asthma prevalence shift from men to women in adolescence. One study showed positive results of focusing on sex-related and gender-related factors in self-regulation education for women. Recent findings imply that enhancing self-regulation and effective management of asthma in women requires attention to sex and gender role influences in clinical counseling and intervention research. SUMMARY: Clinicians may help female patients with asthma by incorporating sex and gender role related considerations into their clinical consultations. Evidence-based asthma education interventions to assist women with their particular asthma management challenges are needed.

Influencia del ejercicio físico en la respuesta inmunitaria en mujeres / Influence of exercise on women's immune response

En los últimos 20 años muchos estudios han propuesto que elejercicio físico provoca cambios en el sistema inmunitario, loque ha hecho posible la creación de la nueva área de investigación“Ejercicio, Estrés e Inmunidad”, ya que además se consideraque los mecanismos de respuesta del sistema inmunitario alejercicio no son muy diferentes a los de respuesta al estrés. Así,el estrés del ejercicio conduce a un incremento proporcional enlos niveles de hormonas de estrés y los cambios concomitantesen diversos aspectos de la inmunidad.Las hormonas sexuales juegan un papel muy importante modulandoel sistema inmunitario, y se han identificado diferencias enla respuesta inmunitaria en relación al género. Dada las diferenciashormonales entre hombres y mujeres y sus diferencias en larespuesta frente al ejercicio, la respuesta inmunitaria innata y/oinflamatoria es frecuentemente más acusada en éstas últimas.Esta mayor reactividad inmunitaria podía ser la causa de que enlas mujeres las enfermedades inflamatorias y/o autoinmunes seanmás frecuentes. Así, un aumento de la respuesta inmunitariainnata debido al ejercicio físico puede prevenir enfermedadesinfecciosas durante el mismo; pero una estimulación exageradade esta respuesta también podría aumentar el riesgo de apariciónde patologías de carácter inflamatorio o exacerbar las mismas.Con esta revisión, hemos pretendido poner de manifiesto que losestudios sobre ejercicio físico e inmunidad en mujeres son todavíamuy escasos y que en muchas ocasiones no presentan igualesrespuestas similares a las observadas en hombres. Este hecho loconsideramos importante sobre todo en mujeres sedentarias, queinician actividades deportivas, para poder evaluar los efectosbeneficiosos o no del ejercicio sobre la inmunidad (AU)

In the last 20 years many studies have proposed that exercisecauses changes on the immune system, this have created a newfield of investigation “Exercise, Stress and Immunity”, since it isconsidered that the immune system mechanisms in response toexercise are not very different to the ones in response to stress.Thus, exercise-induced stress leads to a proportional increase instress hormones and changes on several immunity aspects.Sexual hormones play a key role modulating the immune system,and differences in the immune response in relation to the genderhave been identified. Due to the hormone’s differences betweenmen and women and their different responses to exercise, innate/inflammatory immune response is more marked in women.These greater immune responses could be the reason that inflammatory/autoimmune pathologies are more common in women.So, an increase in the innate immune response due to exercisecould prevent from infectious diseases; but an excessive responsecould also increase the risk to develop these pathologies orexacerbate them.In this review we pretend to show that there is lack of studiesabout exercise and immunity in women, and that in some casesthe responses are not similar to the ones observed in men. Thisfact is important for sedentary women who start sports activities,in order to evaluate the beneficial or non-beneficial effects onimmunity (AU)

Selection of gonadotrophin surge attenuating factor phage antibodies by bioassay.

BACKGROUND: We aimed to combine the generation of "artificial" antibodies with a rat pituitary bioassay as a new strategy to overcome 20 years of difficulties in the purification of gonadotrophin surge-attenuating factor (GnSAF). METHODS: A synthetic single-chain antibody (Tomlinson J) phage display library was bio-panned with partially purified GnSAF produced by cultured human granulosa/luteal cells. The initial screening with a simple binding immunoassay resulted in 8 clones that were further screened using our in-vitro rat monolayer bioassay for GnSAF. Initially the antibodies were screened as pooled phage forms and subsequently as individual, soluble, single-chain antibody (scAbs) forms. Then, in order to improve the stability of the scAbs for immunopurification purposes, and to widen the range of labelled secondary antibodies available, these were engineered into full-length human immunoglobulins. The immunoglobulin with the highest affinity for GnSAF and a previously described rat anti-GnSAF polyclonal antiserum was then used to immunopurify bioactive GnSAF protein. The two purified preparations were electrophoresed on 1-D gels and on 7 cm 2-D gels (pH 4-7). The candidate GnSAF protein bands and spots were then excised for peptide mass mapping. RESULTS: Three of the scAbs recognised GnSAF bioactivity and subsequently one clone of the purified scAb-derived immunoglobulin demonstrated high affinity for GnSAF bioactivity, also binding the molecule in such as way as to block its bioactivity. When used for repeated immunopurification cycles and then Western blot, this antibody enabled the isolation of a GnSAF-bioactive protein band at around 66 kDa. Similar results were achieved using the rat anti-GnSAF polyclonal antiserum. The main candidate molecules identified from the immunopurified material by excision of 2-D gel protein spots was human serum albumin precursor and variants. CONCLUSION: This study demonstrates that the combination of bioassay and phage display technologies is a powerful tool in the study of uncharacterised proteins that defy conventional approaches. In addition, we conclude that these data support suggestions that GnSAF may be structurally related to serum albumin or very tightly bound to serum albumin.

Molecular targets for immunocontraception.

Effective contraception is necessary in countries where limiting population growth has become a public policy imperative. The main antigenic targets for contraceptive vaccine development can be listed as following: 1) sperm antigens, 2) zona pellucida antigens, 3) gonadotrophin-releasing hormone, 4) chorionic gonadotrophin, 5) other protein/peptide hormones (follicle-stimulating hormone, luteinizing hormone, luteinizing hormone-releasing hormone), and 6) gonadal steroid hormones. New techniques, such as the application of monoclonal antibodies, hybridoma and DNA recombinant technologies, have become useful in search for contraceptive candidates. Current state of development of contraceptive vaccines based on specific antigenic targets and trials in animal/human models are presented in this article.