Paternal Retrieval Behavior Regulated by Brain Estrogen Synthetase (Aromatase) in Mouse Sires that Engage in Communicative Interactions with Pairmates

Abstract

Parental behaviors involve complex social recognition and memory processes and interactive behavior with children that can greatly facilitate healthy human family life. Fathers play a substantial role in child care in a small but significant number of mammals, including humans. However, the brain mechanism that controls male parental behavior is much less understood than that controlling female parental behavior. Fathers of non-monogamous laboratory ICR mice are an interesting model for examining the factors that influence paternal responsiveness because sires can exhibit maternal-like parental care (retrieval of pups) when separated from their pups along with their pairmates because of olfactory and auditory signals from the dams. Here we tested whether paternal behavior is related to femininity by the aromatization of testosterone. For this purpose, we measured the immunoreactivity of aromatase [cytochrome P450 family 19 (CYP19)], which synthesizes estrogen from androgen, in nine brain regions of the sire. We observed higher levels of aromatase expression in these areas of the sire brain when they engaged in communicative interactions with dams in separate cages. Interestingly, the number of nuclei with aromatase immunoreactivity in sires left together with maternal mates in the home cage after pup-removing was significantly larger than that in sires housed with a whole family. The capacity of sires to retrieve pups was increased following a period of 5 days spent with the pups as a whole family after parturition, whereas the acquisition of this ability was suppressed in sires treated daily with an aromatase inhibitor. The results demonstrate that the dam significantly stimulates aromatase in the male brain and that the presence of the pups has an inhibitory effect on this increase. These results also suggest that brain aromatization regulates the initiation, development, and maintenance of paternal behavior in the ICR male mice.

Does puberty mark a transition in sensitive periods for plasticity in the associative neocortex?

“…Across various areas of cortex, including the frontal, parietal, and insular cortices, about 96% of cells that express ERbeta are PV+ interneurons, and this represents between 15–27% of total PV+ interneurons (Blurton-Jones and Tuszynski, 2002; Kritzer, 2002). It is important to note that both males and females show this pattern of estrogen receptor expression (Kritzer, 2002); Testosterone may be converted to estradiol via the aromatase enzyme, which is present in the frontal cortex (Akther et al, 2015; Mitra et al, 2015) or the testosterone metabolite, dihydrotestosterone, may be converted to 3beta-diol, which itself can activate ERbeta (Handa et al, 2008). Thus, the rise in either androgens or estrogens at puberty in both sexes may activate frontal cortex ERbeta where it may act as a transcription factor (Heldring et al, 2007) to alter gene expression that may then regulate the physiological properties of PV+ interneurons and change network inhibition.…”

Sex-Specific Differences in Oxytocin Receptor Expression and Function for Parental Behavior

“…Male mice were raised with male littermates and had normal social interactions. [43][44][45] Male and female mice were bred on-site and weaned at P10, then housed in a separate environment not containing any dams or pups before cohousing. Virgin mice (either one male or one female) were then cohoused with a dam and litters ranging from P0-10.…”

Neural Regulation of Paternal Behavior in Mammals: Sensory, Neuroendocrine, and Experiential Influences on the Paternal Brain

“…Implantation of 17β-estradiol-releasing capsules in the MPOA of virgin male rats decreases sensitization latencies (Rosenblatt and Ceus 1998), implicating the MPOA as a site of action for estrogenic activation of paternal care. In ICR mouse fathers, aromatase immunoreactivity is stimulated by cues from the female mate and, more potently, suppressed by cues from pups, in brain regions implicated in paternal care, including the MPOA, MeA, NAcc, and ventral pallidum (Akther et al 2015). Further, suppression of estrogen synthesis by the aromatase inhibitor letrozole inhibits retrieval of related pups by these mouse fathers (Akther et al 2015).…”

“…In ICR mouse fathers, aromatase immunoreactivity is stimulated by cues from the female mate and, more potently, suppressed by cues from pups, in brain regions implicated in paternal care, including the MPOA, MeA, NAcc, and ventral pallidum (Akther et al 2015). Further, suppression of estrogen synthesis by the aromatase inhibitor letrozole inhibits retrieval of related pups by these mouse fathers (Akther et al 2015). Deletion of either the aromatase gene or the ERα gene increases rates of infanticide and/or decreases expression of paternal behavior in male mice, but whether these effects reflect disruption of estrogen signaling in early life or in adulthood is not clear (Matsumoto et al 2003;Ogawa et al 1998).…”