Importance of the matriline for genomic imprinting,brain development and behaviour

Mammalian brain development commences during foeto-placental development and is strongly influenced by the epigenetic regulation of imprinted genes. The foetal placenta exerts considerable influence over the functioning of the adult maternal hypothalamus, and this occurs at the same time as the foetus itself is developing a hypothalamus. Thus, the action and interaction of two genomes in one individual, the mother, has provided a template for co-adaptive functions across generations that are important for maternal care and resource transfer, while co-adaptively shaping the mothering capabilities of each subsequent generation. The neocortex is complex, enabling behavioural diversity and cultural learning such that human individuals are behaviourally unique. Retrotransposons may, in part, be epigenetic mediators of such brain diversity. Interestingly some imprinted genes are themselves retrotransposon-derived, and retrotransposon silencing by DNA methylation is thought to have contributed to the evolutionary origins of imprint control regions. The neocortex has evolved to be adaptable and sustain both short-term and long-term synaptic connections that underpin learning and memory. The adapted changes are not themselves inherited, but the predisposing mechanisms for such epigenetic changes are heritable. This provides each generation with the same ability to make new adaptations while constrained by a transgenerational knowledge-based predisposition to preserve others.     

Pheromones, vomeronasal function, and gender-specific behavior

The striking behavioral phenotypes of mice lacking the TRP2 ion channel have highlighted the importance of the vomeronasal organ in gender-specific sexual behavior.     

Sex difference in attraction thresholds for volatile odors from male and estrous female mouse urine

Volatile urinary odors from opposite sex conspecifics contribute to mate recognition in numerous mammalian species, including mice. We used a simple habituation/dishabituation testing procedure to ask whether the capacity to detect and investigate decreasing concentrations of volatile urinary odors is sexually differentiated in mice. Beginning 2 months after gonadectomy and in the absence of any sex steroid treatment, adult, sexually naive male and female CBA x C57Bl/6 F1 hybrid mice received two series of daily tests that involved the presentation of different dilutions of urine from C57Bl/6 males followed by urine from estrous females. Each test session began with three consecutive presentations of deionized water (10 microl on filter paper for 2 min, behind a mesh barrier which prevented direct physical access, in the home cage at 1-min intervals) followed by three presentations of one of five different dilutions of urine (a different dilution on each test day). Males and females showed equivalent, significant habituation/dishabituation responses (low investigation times for successive water presentations; increased investigation of the first urine stimulus, followed by a decline in successive urine investigation times) to both male and female urine/water dilutions of 1:1, 1:10, and 1:20. However, only female mice responded reliably to 1:40 and 1:80 dilutions of both types of urine, pointing to a sex dimorphism in the detection and/or processing of biologically relevant, volatile urinary odors by the main olfactory system.     

Suppression of prolactin does not reduce infant care by parentally experienced male common marmosets (Callithrix jacchus)

High levels of prolactin have been found to correlate with the expression of paternal care in a variety of taxa. However, in mammals, there is little experimental evidence that prolactin is causally involved in the stimulation or maintenance of paternal care. Here, we suppressed prolactin production in paternally experienced common marmoset fathers in their family groups during the first 2 weeks after their infants were born. Circulating prolactin levels were suppressed using cabergoline (Dostinex: Pfizer), a long acting dopamine (D2) agonist with minimal behavioural side-effects. A within-subject design was used to compare behavioural and hormonal data on 5 paternally experienced fathers during two consecutive births. Cabergoline reduced prolactin to negligible levels in all fathers without effecting testosterone, DHT and cortisol and without adverse side-effects. However, lowering prolactin had no significant effect on the expression of majority of the behaviour patterns associated with paternal care. These included infant carrying, infant grooming and the frequency with which fathers retrieved and rejected infants. The only infant-related behaviour to be affected was the frequency with which fathers touched, licked and investigated infants. We noted a marginally significant increase in this behaviour during cabergoline treatment. Despite the lack of effect on paternal care, cabergoline did exert an effect on the affiliative/sexual behaviour of fathers as there was a significant increase in the grooming behaviour fathers directed at and received from their mates during drug treatment. This study showed that experienced male marmosets can express paternal behaviour in the absence of the high prolactin levels normally seen after infants are born.     

The disparate maternal aunt-uncle ratio in male transsexuals: an explanation invoking genomic imprinting

A significant skewing in the sex ratio in favour of females has been reported for the families of homosexual men such that there are fewer maternal uncles than aunts. This finding is repeated for a large series of transsexual families in this study. Four hundred and seventeen male-to-female transsexuals and 96 female-to-male transsexuals were assessed. Male-to-female transsexuals have a significant excess of maternal aunts vs. uncles. No differences from the expected parity were found for female-to-male transsexuals or on the paternal side. A posited explanation for these findings invokes X inactivation and genes on the X chromosome that escape inactivation but may be imprinted. Our hypothesis incorporates the known familial traits in the families of homosexuals and transsexuals by way of retention of the grand parental epigenotype on the X chromosome. Generation one would be characterized by a failure to erase the paternal imprints on the paternal X chromosome. Daughters of this second generation would produce sons that are XpY and XmY. Since XpY expresses Xist, the X chromosome is silenced and half of the sons are lost at the earliest stages of pregnancy because of the normal requirement for paternal X expression in extra-embryonic tissues. Females survive by virtue of inheriting two X chromosomes, and therefore the possibility of X chromosome counting and choice during embryonic development. In generation three, sons inheriting the paternal X after its second passage through the female germline survive, but half would inherit the feminizing Xp imprinted genes. These genes could pre-dispose the sons to feminization and subsequent development of either homosexuality or transsexualism.     

The accessory olfactory system and its role in the pheromonally mediated suppression of oestrus in grouped mice

Mice were grouped to induce suppression of oestrus and subjected to removal of the vomeronasal organs or treatment with CB 154 which lowers prolactin levels. Both treatments overcame the suppression of oestrus after 72 h. Oestrus suppression was induced in lesioned mice by haloperidol treatment which raises plasma prolactin, and oestrus returned some 72 h after withdrawal of haloperidol treatment.     

Mammalian pheromones: from genes to behaviour

Knocking-out selected genes for receptors of the vomeronasal organ has been found to impair specific aspects of pheromone-induced behaviour in the mouse. This is not unexpected; less predictable is the finding that deleting the gene for a vomeronasal-organ-specific ion channel causes gender blindness.     

Role of the vomeronasal organ and prolactin in the acceleration of puberty in female mice

Young female mice were grouped on Day 21 after birth and subjected to removal of the vomeronasal organ. Soiled bedding from intact adult males failed to advance the onset of first oestrus in these lesioned mice compared to the various control groups. Vomeronasal organ lesions of prepubertal females also prevented increases in uterine weight following exposure to soiled bedding for 48 h on Day 23 when compared to controls. Lowering prolactin by injections of bromocriptine for 48 h on Day 26, but not Day 23, advanced the onset of puberty in intact and vomeronasal organ-lesioned females. Elevating prolactin by injections of domperidone were without effect on the early onset of oestrus when compared to sham-injected controls. It is concluded that marked similarities exist in both the receptor system and neuroendocrine mechanism of male pheromone action observed in prepubertal females and that seen in the adult.