Estradiol‐induced neurogenesis in the female accessory olfactory bulb is required for the learning of the male odor

Abstract

Odors processed by the main and accessory olfactory bulbs (MOB, AOB) are important for sexual behavior. Interestingly, both structures continue to receive new neurons during adulthood. A role for olfactory neurogenesis in sexual behavior in female mice has recently been shown and gonadal hormones such as estradiol can modulate adult neurogenesis. Therefore, we wanted to determine the role of estradiol in learning the odors of sexual partners and in the adult neurogenesis of female aromatase knockout mice (ArKO), unable to produce estradiol. Female wild-type (WT) and ArKO mice were exposed to male odors during 7 days, and olfactory preferences, cell proliferation, cell survival and functional involvement of newborn neurons were analyzed, using BrdU injections, in combination with a marker of cell activation (Zif268) and neuronal fate (doublecortin, NeuN).Behavioral tasks indicated that both WT and ArKO females were able to discriminate between the odors of two different males, but ArKO mice failed to learn the familiar male odor. Proliferation of newborn cells was reduced in ArKO mice only in the dentate gyrus of the hippocampus. Olfactory exposure decreased cell survival in the AOB in WT females, suggesting a role for estradiol in a structure involved in sexual behavior. Finally, newborn neurons do not seem to be functionally involved in the AOB of ArKO mice compared with WT, when females were exposed to the odor of a familiar male, suggesting that estradiol-induced neurogenesis in the AOB is required for the learning of the male odor in female mice.

Effects of Mating and Social Exposure on Cell Proliferation in the Adult Male Prairie Vole (Microtus ochrogaster)

“…These new cells generated by sociosexual stimulation can be integrated into the OB and eventually can be involved in recognition, discrimination, and learning of a conspecific odor [ 36 , 58 , 59 ]. Learning and recognition of the olfactory signature of a conspecific are fundamental in social affiliation and pair bonding in voles [ 10 , 11 ].…”

Sex Steroids and Adult Neurogenesis in the Ventricular-Subventricular Zone

“…Male pheromones stimulate the production of ovarian hormones ( 63 ) as well as the neurogenesis in adult females ( 35 , 64 , 65 ). However, E 2 does not increase neurogenesis ( 66 ), nor cell proliferation in V-SVZ or neuroblasts density in OB, but it decreases cell survival in AOB, but not in MOB ( 24 ).…”

“…This flaw is surprising since steroids have a key role in hippocampal neurogenesis both during development and in adulthood ( 20 – 22 ). Furthermore, V-SVZ-OB system is involved in social and reproductive behaviors, which are strongly regulated by sexual steroids ( 23 , 24 ) and are targets for xenoestrogens ( 25 – 27 ).Moreover, estrogen receptors (ERs) and enzymes involved in the biosynthesis of steroids such as aromatase, the enzyme converting testosterone (T) into estradiol, are expressed in the V-SVZ ( 28 ) and in the OB of adult ( 29 , 30 ) and developing ( 31 ) rats and mice ( 32 ). However, while the importance of steroids in the regulation of adult neurogenesis in the hippocampus has been widely studied, its role in the V-SVZ-OB system is more debated.…”

Cognitive Effects of Aromatase and Possible Role in Memory Disorders

“…Of those groups, ArKO females were the quickest to acquire the ability to recognize volatile urinary odors from ovariectomized (OVX) and E2/progesterone vs. E2 alone-treated females. However, another study showed that while both ArKO and WT female mice can discriminate between odors of two different males, ArKO females failed to learn familiar male odors ( 95 ). This deficit might be due to reduced neurogenesis in the accessory olfactory bulb of ArKO females ( 95 ), suggesting that aromatase conversion of T to E2 is required for neuronal cell proliferation of this brain region in females.…”

“…However, another study showed that while both ArKO and WT female mice can discriminate between odors of two different males, ArKO females failed to learn familiar male odors ( 95 ). This deficit might be due to reduced neurogenesis in the accessory olfactory bulb of ArKO females ( 95 ), suggesting that aromatase conversion of T to E2 is required for neuronal cell proliferation of this brain region in females. Taken together, the findings suggest that ArKO males may have decreased reproductive success because of impaired ability to distinguish individual female smells.…”