Scientists from the University of Tsukuba explored the brain mechanisms that govern the shift from the sexually receptive estrus phase to the non-receptive stage, shedding light on the hormone-driven behavioral changes in female mice throughout their estrous cycle. Their groundbreaking research revealed a neural circuit that triggers a swift reduction in sexually receptive behavior at the close of the estrus period for the very first time.
In social species such as mice, where the females experience a distinct estrous cycle, successful reproduction hinges not just on males recognizing when females are in estrus and engaging in specific mating behaviors, but also on females showing female-specific responses, like accepting or rejecting the advances of males. Female mice are only receptive to males on the day they are in estrus when they are ovulating. However, the details of how females stop showing this receptiveness after the estrus period are not yet fully understood.
The researchers proposed that this change is not merely dictated by hormone levels associated with the estrous state but is actively regulated by a neural mechanism that encourages a decline in sexually receptive behavior. They zoomed in on estrogen receptor beta-positive neurons, which are prevalent in the dorsal raphe nucleus of the midbrain (DRN-ERβ+ cells), as a potential candidate for this brain mechanism.
By utilizing pharmacogenetic methods to inhibit the activity of DRN-ERβ+ cells, the researchers discovered that female mice continued to show high receptivity even the day following estrus, resembling their behavior during estrus. Furthermore, analysis of the DRN-ERβ+ cell activity in female mice showed that these cells were more responsive to male approaches the day after estrus than on the day of estrus, despite a noticeable drop in receptive behavior. The team also established that DRN-ERβ+ cells project to and influence several brain regions that govern the receptive behavior in female mice. The study concludes that a neural circuit originating from DRN-ERβ+ cells plays a significant role in suppressing receptive behavior at the end of the estrus phase within the estrous cycle.
This research was funded through grant-in-aid for Scientific Research 15H05724, 21K18547, and 22H02941 awarded to SO.
