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The mechanisms controlling reproductive hormone secretion are unclear. Here the authors show that noradrenergic inputs to kisspeptin neurons are able to control pulsatile hormone release in a sex- and gonadal steroid-dependent manner.

The role of androgen signalling in avian sexual development is still unclear. This study generated androgen receptor knockout chickens and find that, despite developing typical gonads, the males and females are infertile and many sexual ornaments and behaviors remain underdeveloped in both sexes.

Experience-dependent decision-making is vital for survival. Here, authors uncover how the neuromodulator npr-5 regulates sex- and state-specific learning in C. elegans, shaping behavioral responses.

Here, the authors demonstrate that cortical microstructure in young adults shows marked sex bias, which is most pronounced in paralimbic areas. The effects are put into context with variations in sex hormones and local cytoarchitecture.

In Drosophila, dopamine sets motivational state during mating by regulating the integration of competing drives in copulation decision neurons, potentially indicative of a more general role for control over neuronal integration time in the regulation of behavioural decisions.

Genetic sex introduces variation in phenotypic traits in sexually reproducing organisms. Here, the authors report a developmental gene expression atlas for C. elegans males and hermaphrodites, highlighting the key role of the insulin-like peptide INS-39 in male development and suggesting genetic underpinnings of sexual dimorphism.

Research aimed at improving healthcare has largely focused on male animals and cells. Here, the authors use data from the International Mouse Phenotyping Consortium to show that body weight does not account for all phenotypic differences between male and female mice, supporting more female-focused research.

Vosberg et al. have developed a continuous measure of biological sex in an adolescent cohort, based on quantitative traits of the brain and body. Within each sex, these ‘sex scores’ are associated with sex hormones and personality traits.

The gut microbiome has been reported to be associated with obesity; here, the authors show that there are sex-specific differences in the relationship between gut microbes and abdominal obesity.

Cecilia Lindgren and colleagues report results of a large-scale genome-wide association study for waist-to-hip ratio, a measure of body fat distribution. They identify 13 new loci associated with this trait, several of which show stronger effects in women than in men.

A study maps neuronal genomic targets of oestrogen receptor-α and shows how they coordinate brain sexual differentiation, concluding that the genome remains responsive to hormonal changes after structural dimorphisms have been established.

Le et al. show that, in rodents, females have lower spatial learning threshold before puberty and that sex differences in synaptic plasticity and learning thresholds reverse in the transition to adult life.

Quantitative connectivity matrices (or connectomes) for both adult sexes of the nematode Caenorhabditis elegans are presented that encompass all connections from sensory input to end-organ output across the entire animal.

Autism is ~4 times more common in males. Jung et al. reveal male-preponderant abnormal behaviors in mice lacking CHD8, a chromatin remodeler, accompanying sexually dimorphic changes in neuronal firing, synaptic transmission, and gene expression.

Unlike males, female mice are resistant to hypothalamic inflammation and weight gain when fed a high-fat diet. Here, the authors reveal sex-specific regulation of hypothalamic microglial activation through CX3CR1 signalling, providing a potential mechanism for differential susceptibility to diet-induced obesity.

In mammals, embryos are considered to be sexually indifferent until the action of a sex-determining gene initiates gonadal differentiation. Here it is demonstrated that this situation is different for birds. Using rare, naturally occurring chimaeric chickens where one side of the animal appears male and the other female, it is shown that avian somatic cells possess an inherent sex identity and that, in birds, sexual differentiation is cell autonomous.

fruitless (fru) is an important sex-determinant gene that controls the expression of neuroanatomical sex differences in Drosophila. Here the authors report that a core-promoter factor, TRF2, suppresses a male-type neurite specification through direct interaction with FruBM isoform at the robo1 target gene promoter.

Sexual dimorphism is likely the result of differential gene expression. Here, the authors examine the role of thedsxgene in beetles and find that this gene acts in a sex- and tissue-specific manner, either by regulating sex-specific targets or by acting in opposite directions in males and females.

The medial preoptic area (mPOA) in a mammalian brain is sexually dimorphic, and yet its exact function in mediating gender-specific behavior remains unclear. Here, Xu and colleagues show that optogenetic manipulation of the mPOA in male mice induce female-stereotyped behaviors and vice versa.

Auditory processing is an important component of mosquito behaviour including mating. Here the authors demonstrate substantial sex- and also species-specific variation in mosquito auditory transduction, amplification and gain control.

Mate preference and copulatory behavior in female rodents are coordinated with the ovulation cycles of the animal. This study shows that hypothalamic kisspeptin neurons control both mate choice and copulation, and therefore, that sexual behavior and ovulation may be synchronized by the same neuropeptide.

Olfactory experience can alter the relative abundance of neurons expressing specific chemoreceptors. Here, the authors demonstrate that the distinct odor experiences of sex-separated male and female mice induce sex-specific differences in the abundance of neurons that detect sexually dimorphic odors.

Genes and circuits involved in sleep and sexual arousal have been extensively studied in Drosophila. Here the authors identify the sex determination genes fruitless and doublesex, and a sex-specific P1-DN1 neuronal feedback that governs the interaction between these competing behaviors

Hormone-induced brain masculinization occurs during a perinatal sensitive period but endures into adulthood. Researchers explored DNA methylation as a candidate mechanism. Methylation is higher in female brain and suppresses masculinization genes, which are liberated by hormone-induced reductions in DNMT activity in males. Pharmacological inhibition of DNMTs reduces methylation, masculinizes female brain and behavior and reopens the sensitive period.

In Caenorhabditis elegans, starvation early in life suppresses later sex-specific pruning of synapses through lasting changes in monoaminergic signalling.

A large literature has demonstrated the important role of spinal microglia in chronic pain processing. This paper demonstrates that microglia are required in male but not female mice. In female mice, a similar function appears to be subserved by adaptive immune cell, likely T lymphocytes.

Innate differences between male and female behaviours must be inscribed in their respective genomes, but how these encode distinct neuronal circuits remains largely unclear. Focusing on sex specific responses to the cVA pheromone in fruitflies, a chain of four successive neurons carrying olfactory signals down to motor centres has been identified, with all male to female anatomical differences lying downstream of a conserved sensory cell. The techniques developed should help others in the task of neuronal circuit mapping, which remains daunting even for the relatively simple fly brain.

In this review, the authors discuss the ways in which brain sex difference may arise and provides a model in which genes, hormones and environment can influence the sexual dimorphism of the brain.

Sex-based differences in demographics, clinical features and therapeutic response are emerging in a range of neurological diseases, including movement disorders. The authors review current knowledge of sex-related differences in Parkinson disease, essential tremor, dystonia, Huntington disease and chronic tic disorders.

Understanding the fundamental impact of sex and gender on human health and disease is crucial for optimizing precision medicine. In this Review, Khramtsova, Davis and Stranger discuss the roles of sex in the genetics of complex traits, including genomic evidence for sex-dependent genetic architecture, models and molecular mechanisms of sexually differentiated phenotypes and implications for health care.

Recent years have seen a growing interest in the neurobiological basis of paternal caregiving. Feldman and colleagues review studies that have shed light on the circuits that underlie paternal care in mammals and the consequences of this care for fathers and their offspring.

Sex influences on brain function are emerging in all areas of neuroscience. Jazin and Cahill review sex differences in gene expression in various species and consider the potential mechanisms that underlie these differences, including alternative splicing and epigenetics.

Sex differences in behaviour and disease vulnerability are mirrored by the cellular and molecular sexual dimorphism of the brain. McCarthy and colleagues review findings that have highlighted the roles of inflammation and epigenetics in sex-specific brain differentiation and function.

The differentiation of an organism into a male or female phenotype is a critical developmental process, but the mechanisms that control this decision are remarkably evolutionarily labile. This Review discusses the wide diversity of vertebrate sex-determination mechanisms, their rapid evolution under different forms of genetic and environmental control and the over-arching principles that are shared despite this mechanistic diversity.

In this review, Bale and Epperson discuss the importance of sex differences in stress found at all stages of life. As stress dysregulation is the most common feature across neuropsychiatric diseases, understanding sex differences in stress pathway development and maturation may predict disease risk and resilience factors across the lifespan.