Environmental sex reversal,Trojan sex genes,and sex ratio adjustment: conditions and population consequences

The great diversity of sex determination mechanisms in animals and plants ranges from genetic sex determination (GSD, e.g. mammals, birds, and most dioecious plants) to environmental sex determination (ESD, e.g. many reptiles) and includes a mixture of both, for example when an individual’s genetically determined sex is environmentally reversed during ontogeny (ESR, environmental sex reversal, e.g. many fish and amphibia). ESD and ESR can lead to widely varying and unstable population sex ratios. Populations exposed to conditions such as endocrine‐active substances or temperature shifts may decline over time due to skewed sex ratios, a scenario that may become increasingly relevant with greater anthropogenic interference on watercourses. Continuous exposure of populations to factors causing ESR could lead to the extinction of genetic sex factors and may render a population dependent on the environmental factors that induce the sex change. However, ESR also presents opportunities for population management, especially if the Y or W chromosome is not, or not severely, degenerated. This seems to be the case in many amphibians and fish. Population growth or decline in such species can potentially be controlled through the introduction of so‐called Trojan sex genes carriers, individuals that possess sex chromosomes or genes opposite from what their phenotype predicts. Here, we review the conditions for ESR, its prevalence in natural populations, the resulting physiological and reproductive consequences, and how these may become instrumental for population management.     

Diploidy, evolution and sex

A new gene for a new purpose may be created by mutation of a pre-existing gene. But if that original gene is still required for its original purpose, and is to be retained side by side with the new, a spare copy is needed initially as raw material for the innovation. Thus in haploids the original gene must be duplicated before it is modified. But in diploids a spare copy of every gene is always available, and a mutant allele serving a new purpose can be easily established and maintained by heterosis in parallel with the old allele. Subsequent gene duplication will lead, via crossing-over, to insertion of the new gene in tandem with the old, as a permanent addition to the genome. Calculations show that diploids can thus enlarge their genomes with new genes for new purposes much more readily than haploids; in particular, they can more easily evolve the complex gene control systems characteristic of differentiated multicellular organisms. Sexual reproduction preserves diploidy, and so can be seen as the basis of these richer possibilities for evolutionary innovation.     

Genetic sex determination,sex chromosome size and sex-specific lifespans across tetrapods

Sex differences in lifespan are ubiquitous across the tree of life and exhibit broad taxonomic patterns that remain a puzzle, such as males living longer than females in birds and vice versa in mammals. The prevailing unguarded X hypothesis explains sex differences in lifespan by differential expression of recessive mutations on the X or Z chromosome of the heterogametic sex, but has only received indirect support to date. An alternative hypothesis is that the accumulation of deleterious mutations and repetitive elements on the Y or W chromosome might lower the survival of the heterogametic sex (‘toxic Y’ hypothesis). Here, we use a new database to report lower survival of the heterogametic relative to the homogametic sex across 136 species of birds, mammals, reptiles and amphibians, as expected if sex chromosomes shape sex-specific lifespans, and consistent with previous findings. We also found that the relative sizes of both the X and the Y chromosomes in mammals (but not the Z or the W chromosomes in birds) are associated with sex differences in lifespan, as predicted by the unguarded X and the ‘toxic Y’. Furthermore, we report that the relative size of the Y is negatively associated with male lifespan in mammals, so that small Y size correlates with increased male lifespan. In theory, toxic Y effects are expected to be particularly strong in mammals, and we did not find similar effects in birds. Our results confirm the role of sex chromosomes in explaining sex differences in lifespan across tetrapods and further suggest that, at least in mammals, ‘toxic Y’ effects may play an important part in this role.     

Gender, sex hormones, and vascular tone

The greater incidence of hypertension and coronary artery disease in men and postmenopausal women compared with premenopausal women has been related, in part, to gender differences in vascular tone and possible vascular protective effects of the female sex hormones estrogen and progesterone. However, vascular effects of the male sex hormone testosterone have also been suggested. Estrogen, progesterone, and testosterone receptors have been identified in blood vessels of human and other mammals and have been localized in the plasmalemma, cytosol, and nuclear compartments of various vascular cells, including the endothelium and the smooth muscle. The interaction of sex hormones with cytosolic/nuclear receptors triggers long-term genomic effects that could stimulate endothelial cell growth while inhibiting smooth muscle proliferation. Activation of plasmalemmal sex hormone receptors may trigger acute nongenomic responses that could stimulate endothelium-dependent mechanisms of vascular relaxation such as the nitric oxide-cGMP, prostacyclin-cAMP, and hyperpolarization pathways. Additional endothelium-independent effects of sex hormones may involve inhibition of the signaling mechanisms of vascular smooth muscle contraction such as intracellular Ca2+ concentration and protein kinase C. The sex hormone-induced stimulation of the endothelium-dependent mechanisms of vascular relaxation and inhibition of the mechanisms of vascular smooth muscle contraction may contribute to the gender differences in vascular tone and may represent potential beneficial vascular effects of hormone replacement therapy during natural and surgically induced deficiencies of gonadal hormones.     

Chronotype,gender, and time for sex

The study aimed at testing chronotype and gender differences in the time of day when humans feel the greatest need for sex and the time of day they actually undertake sexual activity. A Polish sample of 565 participants aged between 18 and 57 was tested. In females, regardless of chronotype, the greatest need for sex occurred between 18:00 and 24:00, but a secondary peak appeared only in morning types at 6:00–9:00. In males, the greatest need for sex occurred either in the morning or evening hours: in evening types at 9:00–12:00 and 18:00–3:00; in neither types at 6:00–9:00 and 18:00–24:00; in morning types at 6:00–12:00 and 18:00–24:00. Considering time of day when subjects were undertaking sexual activity most frequently, this appeared between 18:00 and 24:00 for all the participants, and prolonged until 3:00 at night in evening type males. Morningness preference was more strongly related to the timing of need for sex than to the timing of actual sexual activity (r?=??0.275 vs. r?=??0.174), while the timing of desire and the timing of sexual activity were positively, but moderately related (r?=?0.320).     

Cognition, mood disorders, and sex hormones

Macaques (Macaca spp.) are useful models to evaluate effects of ovarian sex steroids and selective estrogen receptor modulators (SERMs) on mood and cognitive function due to similarities to women in their reproductive and central nervous systems. The results of nonhuman primate studies support the hypothesis that estrogen mediates specific aspects of attention and memory, yet much work is needed to understand which cognitive processes are affected, whether natural versus surgical menopause effects are different, and the interaction of age and ovarian senescence on cognitive function. This knowledge is necessary to determine whether to support the cognitive function of women in the menopausal phase of life and, if so, to determine efficacious therapeutic interventions. Mood disorders are prevalent in women and are associated with reproductive function in women and macaques. Exogenous steroid therapies, including oral contraceptives and postmenopausal hormone replacement therapies, have behavioral effects in women and appear to affect the behavior and underlying neural substrates of monkeys. Additional research is necessary to confirm and extend these observations. Ovarian steroids have multiple effects on serotonin synthesis, reuptake, and degradation, on neural activity that drives serotonin release, and on receptor activation in primates. This system modulates cognitive function and mood and is the target of a broad class of antidepressant therapies. Understanding the effects of ovarian steroids on the neural serotonergic system is necessary to understand depression in women. These studies are best carried out in primate models, which are more similar to humans in neural serotonergic function than other animal models.     

Gonadal sex differentiation in Alligator mississippiensis,a species with temperature-dependent sex determination

Temperature of egg incubation determines sex in Alligator mississippiensis hatchlings. To define the timing and morphology of sexual differentiation, alligator gonads were examined histologically and ultrastructurally throughout embryogenesis. At the male-producing temperature (33° C), the onset of testis differentiation occurred in most embryos during developmental stages 21–22, when a number of somatic cells in the medulla of the gonad became enlarged, forming presumptive Sertoli cells. Some enlarged somatic cells were also observed at the female-producing temperature (30° C) during gonadogenesis, but they were less widespread than at 33° C. Ovarian differentiation at 30° C began slighlty later, during stage 22–23, and was characterised by proliferation of germs cells in the cortex of the gonad. Testis formation in alligators may depend upon presumptive Sertoli cells differentiating prior to a critical event in embryogenesis, such as germ cell proliferation and meiosis. If follows that ovary formation occurs if this requirement is not met, as at lower incubation temperatures.     

Delayed pollination,stigma length,sex expression,and progeny sex ratio in spinach,Spinacea oleracea (Chenopodiaceae)

Delayed outcrossed pollination of female spinach plants (Spinacea oleracea L.) resulted in increased stigma length and a male-biased progeny sex ratio. One group of females was outcrossed 10–14 d after anthesis, a second group was never outcrossed, and a third group, the control, consisted of females that were outcrossed as soon as stigmas appeared. Stigma length was significantly greater for plants in the delayed and never outcrossed groups compared to the control. Furthermore, stigmas of virgin flowers grew until they were either pollinated or the plants produced anthers. Plants that were never outcrossed produced their own anthers and self pollinated. The resulting progeny were all female. The sons of the delayed outcrossed group produced more stamens, on average, than sons of the control group. The observed male-biased sex ratio among the progeny of delayed outcrossed plants could be due to gametic selection. To test for this, plants were held virgin until their stigmas reached a length of at least 3 mm. These stigmas were then pollinated either distally or proximally. No significant difference was found between the progeny sex ratios of these two treatments. However, both sex ratios were more male biased than progeny of plants pollinated the day of anthesis (control group of the first experiment). We conclude that maternal factors, rather than gametophytic selection, may be responsible for the male-biased sex ratio observed in the first experiment.     

Human IgG Fc-glycosylation profiling reveals associations with age, sex, female sex hormones and thyroid cancer

IgG functions rely on interactions of the Fc region with other proteins, which are optimized by tailoring of a conserved N-linked glycosylation at Asn-297. We conducted a study involving 735 control individuals and 138 thyroid cancer patients. Here we demonstrated that previously described age-related change in Fc-glycosylation was further characterized by definite sex specificity. In females, the incidences of most of glycosylated forms began to pose characteristic changes at ages of puberty or menopause. In addition, glycan-glycan relationships existed extensively within Fc glycosylation, which were characterized to be altered upon different states of subjects, such as age, sex and thyroid cancer. In thyroid cancer patients, detailed comparison of glycosylation incidences with control individuals yielded insight into aberrant change in IgG(1) Fc-glycosylation. This aberrant pattern was also featured by remarkable specificities of both age and sex. The receiver operating characteristic curve analysis was used to determine diagnostic values of Fc glycosylation. Finally, clinical measurement of two major female sex hormones estradiol and progesterone was conducted to determine potential associations of hormones with IgG Fc glycosylation. This study provided an important view to the associations of IgG Fc N-linked glycosylation with age, sex, female sex hormones and thyroid cancer. This article is part of a Special Issue entitled: Proteomics: The clinical link.