Of marsupials and men: "Backdoor" dihydrotestosterone synthesis in male sexual differentiation

Following development of the fetal bipotential gonad into a testis, male genital differentiation requires testicular androgens. Fetal Leydig cells produce testosterone that is converted to dihydrotestosterone in genital skin, resulting in labio-scrotal fusion. An alternative 'backdoor' pathway of dihydrotestosterone synthesis that bypasses testosterone has been described in marsupials, but its relevance to human biology has been uncertain. The classic and backdoor pathways share many enzymes, but a 3α-reductase, AKR1C2, is unique to the backdoor pathway. Human AKR1C2 mutations cause disordered sexual differentiation, lending weight to the idea that both pathways are required for normal human male genital development. These observations indicate that fetal dihydrotestosterone acts both as a hormone and as a paracrine factor, substantially revising the classic paradigm for fetal male sexual development.

Species-Specific Relationships between Water Transparency and Male Coloration within and between Two Closely Related Lake Victoria Cichlid Species

Environmental variation in signalling conditions affects animal communication traits, with possible consequences for sexual selection and reproductive isolation. Using spectrophotometry, we studied how male coloration within and between populations of two closely related Lake Victoria cichlid species (Pundamilia pundamilia and P. nyererei) covaries with water transparency. Focusing on coloration patches implicated in sexual selection, we predicted that in clear waters, with broad-spectrum light, (1) colours should become more saturated and (2) shift in hue away from the dominant ambient wavelengths, compared to more turbid waters. We found support for these predictions for the red and yellow coloration of P. nyererei but not the blue coloration of P. pundamilia. This may be explained by the species difference in depth distribution, which generates a steeper gradient in visual conditions for P. nyererei compared to P. pundamilia. Alternatively, the importance of male coloration in intraspecific sexual selection may differ between the species. We also found that anal fin spots, that is, the orange spots on male haplochromine anal fins that presumably mimic eggs, covaried with water transparency in a similar way for both species. This is in contrast to the other body regions studied and suggests that, while indeed functioning as signals, these spots may not play a role in species differentiation.

Differentiation in Male and Female Speech Styles

From the moment of their birth, a person's life is determined by their sex. Ms. Goroshko wants to know why this difference is so striking, why society is so concerned to sustain it, and how it is able to persist even when certain national or behavioural stereotypes are erased between people. She is convinced of the existence of not only social, but biological differences between men and women, and set herself the task, in a manuscript totalling 126 pages, written in Ukrainian and including extensive illustrations, of analysing these distinctions as they are manifested in language. She points out that, even before 1900, certain stylistic differences between the ways that men and women speak had been noted. Since then it has become possible, for instance in the case of Japanese, to point to examples of male and female sub-languages. In general, one can single out the following characteristics. Males tend to write with less fluency, to refer to events in a verb-phrase, to be time-oriented, to involve themselves more in their references to events, to locate events in their personal sphere of activity, and to refer less to others. Therefore, concludes Ms Goroshko, the male is shown to be more active, more ego-involved in what he does, and less concerned about others. Women, in contrast, were more fluent, referred to events in a noun-phrase, were less time-oriented, tended to be less involved in their event-references, locate events within their interactive community and refer more to others. They spent much more time discussing personal and domestic subjects, relationship problems, family, health and reproductive matters, weight, food and clothing, men, and other women. As regards discourse strategies, Ms Goroshko notes the following. Men more often begin a conversation, they make more utterances, these utterances are longer, they make more assertions, speak less carefully, generally determine the topic of conversation, speak more impersonally, use more vulgar expressions, and use fewer diminutives and more imperatives. Women's speech strategies, apart from being the opposite of those enumerated above, also contain more euphemisms, polite forms, apologies, laughter and crying. All of the above leads Ms. Goroshko to conclude that the differences between male and female speech forms are more striking than the similarities. Furthermore she is convinced that the biological divergence between the sexes is what generates the verbal divergence, and that social factors can only intensify or diminish the differentiation in verbal behaviour established by the sex of a person. Bearing all this in mind, Ms Goroshko set out to construct a grammar of male and female styles of speaking within Russian. One of her most important research tools was a certain type of free association test. She took a list comprising twelve stimuli (to love, to have, to speak, to fuck, a man, a woman, a child, the sky, a prayer, green, beautiful) and gave it to a group of participants specially selected, according to a preliminary psychological testing, for the high levels of masculinity or femininity they displayed. Preliminary responses revealed that the female reactions were more diverse than the male ones, there were more sentences and word combinations in the female reactions, men gave more negative responses to the stimulus and sometimes didn't want to react at all, women reacted more to adjectives and men to nouns, and that, surprisingly, women coloured more negatively their reactions to the words man, to love and a child (Ms. Goroshko is inclined to attribute this to the present economic situation in Russia). Another test performed by Ms. Goroshko was the so-called "defective text" developed by A.A. Brudny. All participants were distributed with packets of complete sentences, which had been taken from a text and then mixed at random. The task was to reconstruct the original text. There were three types of test, the first descriptive, the second narrative, and the third logical. Ms. Goroshko created computer programmes to analyse the results. She found that none of the reconstructed texts was coincident with the original, differing both from the original text and amongst themselves and that there were many more disparities in the male than the female texts. In the descriptive and logical texts the differences manifested themselves more clearly in the male texts, and in the narrative texts in the female texts. The widest dispersal of values was observed at the outset, while the female text ending was practically coincident with the original (in contrast to the male ending). The greatest differences in text reconstruction for both males and females were registered in the middle of the texts. Women, Ms. Goroshko claims, were more sensitive to the semantic structure of the texts, since they assembled the narrative text much more accurately than the other two, while the men assembled more accurately the logical text. Texts written by women were assembled more accurately by women and texts by men by men. On the basis of computer analysis, Ms. Goroshko found that female speech was substantially more emotional. It was expressed by various means, hyperbole, metaphor, comparisons, epithets, ways of enumeration, and with the aid of interjections, rhetorical questions, exclamations. The level of literacy was higher for female speech, and there were fewer mistakes in grammar and spelling in female texts. The last stage of Ms Goroshko's research concerned the social stereotypes of beliefs about men and women in Russian society today. A large number of respondents were asked questions such as "What merits must a woman possess?", "What are male vices and virtues?", etc. After statistical manipulation, an image of modern man and woman, as it exists in the minds of modern Russian men and women, emerged. Ms. Goroshko believes that her findings are significant not only within the field of linguistics. She has already successfully worked on anonymous texts and been able to decide on the sex of the author and consequently believes that in the future her research may even be of benefit to forensic science.

Mesenchymal stem cell therapy following muscle trauma leads to improved muscular regeneration in both male and female rats

Mesenchymal stem cell (MSC) therapy has the potential to enhance muscular regeneration. In previous publications, our group was able to show a dose-response relationship in female animals between the amount of transplanted cells and muscle force. The impact of sex on the regeneration of musculoskeletal injuries following MSC transplantation remains unclear.

Primary male osteoporosis is associated with enhanced glucocorticoid availability

OBJECTIVE: While systemic glucocorticoids compromise bone metabolism, altered intracellular cortisol availability may also contribute to the pathogenesis of primary male osteoporosis (MO). The objective of this study was to assess whether intracellular cortisol availability is increased in MO due to a distorted local cortisol metabolism. METHODS: Forty-one patients with MO were compared with age- and BMI-matched non-osteoporotic subjects after excluding overt systemic hypercortisolism (N = 41). Cortisol, cortisone and the respective tetrahydro-, 5α-tetrahydro- and total cortisol metabolites were analysed by GC-MS in 24 h urine. Apparent 11β-hydroxysteroid dehydrogenase (11β-HSD) enzyme activities, excretion of cortisol metabolites and calcium, and fractional urinary calcium excretion were assessed and related to BMD. RESULTS: Fractional and total urinary calcium excretion negatively correlated with BMD at all (P < 0.05) and at three of five (P < 0.05) measurement sites, respectively. While systemic cortisol was unchanged, apparent 11β-HSD enzyme activity in MO patients (P < 0.01) suggested increased intracellular cortisol availability. Total and fractional urinary calcium excretion was higher, with apparent 11β-HSD enzyme activities consistent with an enhanced intracellular cortisol availability (P < 0.05). CONCLUSION: Apparent 11β-HSD enzyme activities consistent with increased intracellular cortisol availability correlated with urinary calcium loss and reduced bone mineral density in MO. The changes in 11β-HSD activity were associated with both the fractional calcium excretion, suggesting altered renal calcium handling, and the absolute urinary calcium excretion. Both mechanisms could result in a marked bone calcium deficiency if insufficiently compensated for by intestinal calcium uptake.

Steroid hormone related male biased parasitism in chamois, Rupicapra rupicapra rupicapra

Parasites are linked with their host in a trophic interaction with implications for both hosts and parasites. Interaction stretches from the host's immune response to the structuring of communities and the evolution of biodiversity. As in many species sex determines life history strategy, response to parasites may be sex-specific. Males of vertebrate species tend to exhibit higher rates of parasites than females. Sex-associated hormones may influence immunocompetence and are hypothesised to lead to this bias. In a field study, we tested the prediction of male biased parasitism (MBP) in free ranging chamois (Rupicapra rupicapra rupicapra), which are infested intensely by gastrointestinal and lung helminths. We further investigated sex differences in faecal androgen (testosterone and epiandrosterone), cortisol and oestrogen metabolites using enzyme immunoassays (EIA) to evaluate the impact of these hormones on sex dependent parasite susceptibility. Non-invasive methods were used and the study was conducted throughout a year to detect seasonal patterns. Hormone levels and parasite counts varied significantly throughout the year. Male chamois had a higher output of gastrointestinal eggs and lungworm larvae when compared to females. The hypothesis of MBP originating in sex related hormone levels was confirmed for the elevated output of lungworm larvae, but not for the gastrointestinal nematodes. The faecal output of lungworm larvae was significantly correlated with androgen and cortisol metabolite levels. Our study shows that sex differences in steroid levels play an important role to explain MBP, although they alone cannot fully explain the phenomenon.

Differential expression of IGF-I mRNA and peptide in the male and female gonad during early development of a bony fish, the tilapia Oreochromis niloticus

Insulin-like growth factor I (IGF-I) plays a key role in the complex system that regulates bony fish growth, differentiation, and reproduction. The major source of circulating IGF-I is liver, but IGF-I-producing cells also occur in other organs, including the gonads. Because no data are available on the potential production sites of IGF-I in gonad development, developmental stages of monosex breedings of male and female tilapia from 0 day postfertilization (DPF) to 90 DPF were investigated for the production sites of IGF-I at the peptide (immunohistochemistry) and mRNA (in situ hybridization) level. IGF-I mRNA first appeared in somatic cells of the male and female gonad anlage at 7 DPF followed by IGF-I peptide around 9-10 DPF. Gonad anlagen were detected from 7 DPF. Starting at 7 DPF, IGF-I peptide but no IGF-I mRNA was observed in male and female primordial germ cells (PGCs) provided that IGF-I mRNA was not under the detection level, this observation may suggest that IGF-I originates from the somatic cells and is transferred to the PGCs or is of maternal origin. While in female germ cells IGF-I mRNA and peptide appeared at 29 DPF, in male germ cells both were detected as late as at 51-53 DPF. It is assumed that the production of IGF-I in the germ cells is linked to the onset of meiosis that in tilapia ovary starts at around 28 DPF and in testes at around 52-53 DPF. In adult testis, IGF-I mRNA and peptide occurred in the majority of spermatogonia and spermatocytes as well as in Leydig cells, the latter indicating a role of IGF-I in the synthesis of male sex steroids. In adult ovary, IGF-I mRNA and IGF-I peptide were always present in small and previtellogenic oocytes but only IGF-I peptide infrequently occurred in oocytes at the later stages. IGF-I expression appeared in numerous granulosa and some theca cells of follicles at the lipid stage and persisted in follicles with mature oocytes. The results suggest a crucial role of local IGF-I in the formation, differentiation and function of tilapia gonads.

A Mechanistic Latent Variable Model for Estimating Drug Concentrations in the Male Genital Tract

The purpose of this study is to develop statistical methodology to facilitate indirect estimation of the concentration of antiretroviral drugs and viral loads in the prostate gland and the seminal vesicle. The differences in antiretroviral drug concentrations in these organs may lead to suboptimal concentrations in one gland compared to the other. Suboptimal levels of the antiretroviral drugs will not be able to fully suppress the virus in that gland, lead to a source of sexually transmissible virus and increase the chance of selecting for drug resistant virus. This information may be useful selecting antiretroviral drug regimen that will achieve optimal concentrations in most of male genital tract glands. Using fractionally collected semen ejaculates, Lundquist (1949) measured levels of surrogate markers in each fraction that are uniquely produced by specific male accessory glands. To determine the original glandular concentrations of the surrogate markers, Lundquist solved a simultaneous series of linear equations. This method has several limitations. In particular, it does not yield a unique solution, it does not address measurement error, and it disregards inter-subject variability in the parameters. To cope with these limitations, we developed a mechanistic latent variable model based on the physiology of the male genital tract and surrogate markers. We employ a Bayesian approach and perform a sensitivity analysis with regard to the distributional assumptions on the random effects and priors. The model and Bayesian approach is validated on experimental data where the concentration of a drug should be (biologically) differentially distributed between the two glands. In this example, the Bayesian model-based conclusions are found to be robust to model specification and this hierarchical approach leads to more scientifically valid conclusions than the original methodology. In particular, unlike existing methods, the proposed model based approach was not affected by a common form of outliers.

The horse genome project - sequence based insights into male reproductive mechanisms

The growing knowledge on physiology, cell biology and biochemistry of the reproductive organs has provided many insights into molecular mechanisms that are required for successful reproduction. Research directed at the investigation of reproduction physiology in domestic animals was hampered in the past by a lack of species-specific genomic information. The genome sequences of dog, cattle and horse have become publicly available in 2005, 2006 and 2007 respectively. Although the gene content of mammalian genomes is generally very similar, genes involved in reproduction tend to be less conserved than the average mammalian gene. The availability of genome sequences provides a valuable resource to check whether any protein that may be known from human or mouse research is present in cattle and/or horse as well. Currently there are more than 200 genes known that are involved in the production of fertile sperm cells. Great progress has been made in the understanding of genetic aberrations that lead to male infertility. Additionally, the first genetic mechanisms are being discovered that contribute to the quantitative variation of fertility traits in fertile male animals. Here, I will review some selected aspects of genetic research in male fertility and offer some perspectives for the use of genomic sequence information.