A Sexually Dimorphic Area of the Dorsal Hypothalamus in Mice and Common Marmosets

Abstract

We found a novel sexually dimorphic area (SDA) in the dorsal hypothalamus (DH) of mice. The SDA-DH was sandwiched between 2 known male-biased sexually dimorphic nuclei, the principal nucleus of the bed nucleus of the stria terminalis and the calbindin-sexually dimorphic nucleus, and exhibited a female-biased sex difference in neuronal cell density. The density of neurons in the SDA-DH was increased in male mice by orchidectomy on the day of birth and decreased in female mice by treatment with testosterone, dihydrotestosterone, or estradiol within 5 days after birth. These findings indicate that the SDA-DH is defeminized under the influence of testicular testosterone, which acts via both directly by binding to the androgen receptor, and indirectly by binding to the estrogen receptor after aromatization. We measured the activity of SDA-DH neurons with c-Fos, a neuronal activity marker, in female mice during maternal and sexual behaviors. The number of c-Fos-expressing neurons in the SDA-DH of female mice was negatively correlated with maternal behavior performance. However, the number of c-Fos-expressing neurons did not change during female sexual behavior. These findings suggest that the SDA-DH contains a neuronal cell population, the activity of which decreases in females exhibiting higher performance of maternal behavior, but it may contribute less to female sexual behavior. Additionally, we examined the brain of common marmosets and found an area that appears to be homologous with the mouse SDA-DH. The sexually dimorphic structure identified in this study is not specific to mice and may be found in other species.

Signatures of sex: Sex differences in gene expression in the vertebrate brain

“…The ontogeny of sex‐typical expression patterns may be identified by integrating data from multiple epigenomic assays, which should reveal sex‐specific regulatory elements and their interacting TFs (Gray et al, ; Nord, Pattabiraman, Visel, & Rubenstein, ). Application of these approaches to the developing human brain is already underway (Ecker et al, ; Li et al, ; Wang et al, ) and likely to reveal conserved sex‐biased or hormone‐regulated gene programs (Hoffman et al, ; Ijaz & Hoffman, ; Miller et al, ; Moe et al, ). Subsequent research in model organisms can then dissect the contribution of molecular sex differences to the development and function of specific neural pathways.…”

Moxd1 Is a Marker for Sexual Dimorphism in the Medial Preoptic Area, Bed Nucleus of the Stria Terminalis and Medial Amygdala

“…Moxd1 is abundantly expressed in the SDN-POA, BNSTpr and MePD in a sexually dimorphic manner, where the cell number and volume show a male-biased sex difference which is determined by high testosterone level during the perinatal period (Gilmore et al, 2012; Campi et al, 2013; Moe et al, 2016a). Among these nuclei, BNSTpr and MePD are included in the medial extended amygdala, which serve male reproductive circuits via pheromonal inputs from accessary olfactory bulb and contain various sexually dimorphic structures (Newman, 1999; de Olmos and Heimer, 1999; Martínez-García et al, 2012).…”

“…However, the sexual dimorphism of the SDN-POA in laboratory mice was not recognized or was very subtle in Nissl-stained sections (Young, 1982; Brown et al, 1999). Recently, calbindin has been used to visualize the SDN-POA in mice as well as rats, musk shrews and common marmosets in a sexually dimorphic pattern (Sickel and McCarthy, 2000; Edelmann et al, 2007; Bodo and Rissman, 2008; Orikasa and Sakuma, 2010; Jahan et al, 2015; Moe et al, 2016a,b). The sexual dimorphism of calbindin-ir cells in the MPOA depends on the presence of testosterone during the neonatal period and is independent of the gonadal steroid hormone level in adult animals (Sickel and McCarthy, 2000; Orikasa and Sakuma, 2010).…”

“…The cluster of calbindin-immunoreactive (ir) cells in the MPOA also shows sex differences and responsiveness to perinatal hormones (Bodo and Rissman, 2008; Orikasa and Sakuma, 2010). Additionally, sex differences in calbindin-ir cells of the MPOA have been demonstrated in musk shrews and common marmosets (Moe et al, 2016a,b). …”

Estrogenic regulation of social behavior and sexually dimorphic brain formation

“…As mentioned before, the BNSTpv of female mice is larger in volume and contains more neuron numbers compared to the BNSTpv of male mice. Additionally, the BNSTp may exhibit a female-dominant sex difference in ERα expression, because the dorsal hypothalamic area corresponding to the BNSTpv has more cells expressing ERα and shows a higher expression level of ERα in female mice than in male mice (Moe et al, 2016a). Physiological functions of the BNSTpv are largely unknown.…”