Sexually dimorphic oxytocin receptor-expressing neurons in the preoptic area of the mouse brain

Abstract

Oxytocin is involved in the regulation of social behaviors including parental behaviors in a variety of species. Oxytocin triggers social behaviors by binding to oxytocin receptors (OXTRs) in various parts of the brain. OXTRs are present in the preoptic area (POA) where hormone-sensitive sexually dimorphic nuclei exist. The present study was conducted to examine whether sex differences exist in the distribution of neurons expressing OXTRs in the POA. Using OXTR-Venus (an enhanced variant of yellow fluorescent protein) mice, the distribution of OXTR-Venus cells in the POA was compared between sexes. The total number of OXTR-Venus cells in the medial POA (MPOA) was significantly greater in females than in males. No detectable OXTR-Venus cells were observed in the anteroventral periventricular nucleus (AVPV) within the MPOA in most of the brain sections from males. We further examined the total number of OXTR-Venus cells in the AVPV and the rest of the MPOA between the sexes. The total number of OXTR-Venus cells in the AVPV in females (615 ± 43) was significantly greater than that in males (14 ± 2), whereas the total number of OXTR-Venus cells in the rest of the MPOA did not differ significantly between the sexes. Thus, the sexually dimorphic expression of OXTR-Venus specifically occurred in the AVPV, but not in the rest of the MPOA. We also examined whether the expression of OXTR in the AVPV is driven by the female gonadal hormone, estrogen. Immunocytochemistry and single-cell RT-PCR revealed the presence of the estrogen receptor α in OXTR-Venus cells in the female AVPV. Moreover, ovariectomy resulted in the absence of OXTR-Venus expression in the AVPV, whereas estrogen replacement therapy restored OXTR-Venus expression. These results demonstrate that the expression of OXTR in the AVPV is primarily female specific and estrogen dependent. The presence of the sexually dimorphic expression of OXTR in the AVPV suggests the involvement of OXTR neurons in the AVPV in the regulation of female-specific behavior and/or physiology.

Quantitative cellular-resolution map of the oxytocin receptor in postnatally developing mouse brains

“…In contrast, the hypothalamic area showed a continuous increase into adulthood with sexually dimorphic expression of OTR in the PMv and AVPV, parts of the hypothalamic behavioral control column that generates sexually motivated behavior 38 . This suggests that OTR in hypothalamic nuclei plays a role in generating sex-specific behavior during sexual maturation 36,44,61 .…”

Quantitative Cellular-Resolution Map of the Oxytocin Receptor in Postnatally Developing Mouse Brains

“…In contrast, the anteroventral periventricular nucleus (AVPV) near the medial preoptic area showed higher OTR expression in females than males at P56, but not before (Figure 7B). A recent study identified abundant estrogen-dependent OTR expressing cells in the AVPV, co-expressing estrogen receptor in female mice 36 . This result suggests a potential role of OTR in sexual behavior 36–38 .…”

“…A recent study identified abundant estrogen-dependent OTR expressing cells in the AVPV, co-expressing estrogen receptor in female mice 36 . This result suggests a potential role of OTR in sexual behavior 36–38 .…”

“…In contrast, the hypothalamic area showed a continuous increase into adulthood with sexually dimorphic expression of OTR in the PMv and AVPV, parts of the hypothalamic behavioral control column that generates sexually motivated behavior 38 . This suggests that OTR in hypothalamic nuclei plays a role in generating sex-specific behavior during sexual maturation 36,40,57 .…”

Involvement of Oxytocin Receptor/Erk/MAPK Signaling in the mPFC in Early Life Stress-Induced Autistic-Like Behaviors

“…OT is released in the paraventricular nucleus and supraoptic nucleus of the hypothalamus in the brain and also implicated in regulating the social behaviors besides mating, maternal behavior, attachment, aggression, and sexual behavior. Recent studies have demonstrated that OT produces anxiolytic, antidepressant, and pro-social effects in animal models ( Ferguson et al, 2001 ; Heinrichs et al, 2003 ; Sharma et al, 2019 ). Due to its functions on the improvement of social recognition, the intranasal administration of OT has been under clinical studies for the treatment of ASD characterized by social deficits in adults and juveniles ( Anagnostou et al, 2012 ).…”