Authors: Kathryn M. Lenz1,2,3,4* Lindsay A. Pickett5,6, Christopher L. Wright5,6, Katherine T. Davis5,6, Anabel Galan1,2,3, Margaret M. McCarthy5,6
“It’s fascinating to watch, because these masculine females don’t have the hardware to engage in male reproductive behavior, but you wouldn’t know it from the way they act. They appear to be strongly motivated to try to engage in male sexual behavior with other females,”
"The study focused on the pre-optic area of the brain, which is part of the hypothalamus."
“This is the most sexually dynamic area of the brain — we know that it’s highly important for male-type reproductive and social behaviors such as mounting and for initiating maternal behavior in female animals,”
said Lenz
Abstract
Many sex differences in brain and behavior are programmed during development by gonadal hormones, but the cellular mechanisms are incompletely understood. We found that immune system-derived mast cells are a primary target for the masculinizing hormone, estradiol, and that mast cells are in turn primary mediators of brain sexual differentiation. Newborn male rats had greater numbers and more activated mast cells in the preoptic area (POA), a brain region essential for male copulatory behavior, than female littermates during the critical period for sexual differentiation. Inhibiting mast cells with a stabilizing agent blunted the masculinization of both POA neuronal and microglial morphology and adult sex behavior, while activating mast cells in females, even though fewer in number, induced masculinization. Treatment of newborn females with a masculinizing dose of estradiol increased mast cell number and induced mast cells to release histamine, which then stimulated microglia to release prostaglandins and thereby induced male-typical synaptic patterning. These findings identify a novel non-neuronal origin of brain sex differences and resulting motivated behaviors.
Results
"We found that there are more mast cells in the POA neuropil and adjacent leptomeninges of neonatal male rats than females during the critical window for sexual differentiation (Fig. 1A-B). Thereafter, the mast cell population in males decreases to female levels (Fig. 1B). To determine if this sex difference is hormonally mediated, newborn females were treated with a dose of 17β-estradiol that mimics the levels normally seen in males (8) and the effect on mast cells was measured within 2 days. Mast cells are located in the neuropil and meninges of the POA as well as in the velum interpositum near the hippocampus (Fig. 1C). The overall number of mast cells (Fig. 1D) and the number in the neuropil (Fig. 1E) were increased to male levels in females treated with a masculinizing dose of estradiol. Mast cells release secretory vesicles filled with bioactive mediators via a process called degranulation (7). The number of mast cells with evidence of degranulation was not different between males and females on postnatal day (PN) 2, which is after the fetal male androgen surge, but exogenous estradiol induced acute increases in the percent of total mast cells showing degranulation in females (Fig. 1D, shaded bars). In agreement, males had a higher percentage of mast cells with evidence of degranulation than females on embryonic day 20, when estradiol is endogenously high in males due to the testicular hormone surge"
Discussion
"Our data suggest that mast cells basally contribute to the masculinization process in males, as mast cell inhibition decreased male-typical sexual behavior in adulthood."
"We further identified histamine as a mast cell-derived mediator that induces masculinization of microglia and dendritic spine endpoints, and likely impacts the masculinization process by stimulating microglia to release PGE2, which we have previously identified as the major molecular signal driving masculinization of the POA and male-typical sexual behavior"
"We found females can be masculinized by an allergic response in the pregnant dam"
"Indeed, our data indicates that males that experience allergic inflammation in utero show evidence of modest dysmasculinization in microglia, dendritic spines, and behavior. This may reflect an optimal threshold for inflammatory signaling in the male brain, beyond which there is dysregulated sociosexual development. Moreover, this dysmasculinization occurred even though allergen exposure further increased mast cell degranulation in males, which underscores that mast cells are likely just one of many potential modulatory systems that influence the sexual differentiation process in males."
I wish @lvysaur, @Such_Saturation, @Travis, @Amazoniac, @Salmonamb, @Wagner83 et alia. Find interesting!
https://www.biorxiv.org/content/biorxiv/early/2017/10/19/205559.full.pdf
“It’s fascinating to watch, because these masculine females don’t have the hardware to engage in male reproductive behavior, but you wouldn’t know it from the way they act. They appear to be strongly motivated to try to engage in male sexual behavior with other females,”
"The study focused on the pre-optic area of the brain, which is part of the hypothalamus."
“This is the most sexually dynamic area of the brain — we know that it’s highly important for male-type reproductive and social behaviors such as mounting and for initiating maternal behavior in female animals,”
said Lenz
Abstract
Many sex differences in brain and behavior are programmed during development by gonadal hormones, but the cellular mechanisms are incompletely understood. We found that immune system-derived mast cells are a primary target for the masculinizing hormone, estradiol, and that mast cells are in turn primary mediators of brain sexual differentiation. Newborn male rats had greater numbers and more activated mast cells in the preoptic area (POA), a brain region essential for male copulatory behavior, than female littermates during the critical period for sexual differentiation. Inhibiting mast cells with a stabilizing agent blunted the masculinization of both POA neuronal and microglial morphology and adult sex behavior, while activating mast cells in females, even though fewer in number, induced masculinization. Treatment of newborn females with a masculinizing dose of estradiol increased mast cell number and induced mast cells to release histamine, which then stimulated microglia to release prostaglandins and thereby induced male-typical synaptic patterning. These findings identify a novel non-neuronal origin of brain sex differences and resulting motivated behaviors.
Results
"We found that there are more mast cells in the POA neuropil and adjacent leptomeninges of neonatal male rats than females during the critical window for sexual differentiation (Fig. 1A-B). Thereafter, the mast cell population in males decreases to female levels (Fig. 1B). To determine if this sex difference is hormonally mediated, newborn females were treated with a dose of 17β-estradiol that mimics the levels normally seen in males (8) and the effect on mast cells was measured within 2 days. Mast cells are located in the neuropil and meninges of the POA as well as in the velum interpositum near the hippocampus (Fig. 1C). The overall number of mast cells (Fig. 1D) and the number in the neuropil (Fig. 1E) were increased to male levels in females treated with a masculinizing dose of estradiol. Mast cells release secretory vesicles filled with bioactive mediators via a process called degranulation (7). The number of mast cells with evidence of degranulation was not different between males and females on postnatal day (PN) 2, which is after the fetal male androgen surge, but exogenous estradiol induced acute increases in the percent of total mast cells showing degranulation in females (Fig. 1D, shaded bars). In agreement, males had a higher percentage of mast cells with evidence of degranulation than females on embryonic day 20, when estradiol is endogenously high in males due to the testicular hormone surge"
Discussion
"Our data suggest that mast cells basally contribute to the masculinization process in males, as mast cell inhibition decreased male-typical sexual behavior in adulthood."
"We further identified histamine as a mast cell-derived mediator that induces masculinization of microglia and dendritic spine endpoints, and likely impacts the masculinization process by stimulating microglia to release PGE2, which we have previously identified as the major molecular signal driving masculinization of the POA and male-typical sexual behavior"
"We found females can be masculinized by an allergic response in the pregnant dam"
"Indeed, our data indicates that males that experience allergic inflammation in utero show evidence of modest dysmasculinization in microglia, dendritic spines, and behavior. This may reflect an optimal threshold for inflammatory signaling in the male brain, beyond which there is dysregulated sociosexual development. Moreover, this dysmasculinization occurred even though allergen exposure further increased mast cell degranulation in males, which underscores that mast cells are likely just one of many potential modulatory systems that influence the sexual differentiation process in males."
I wish @lvysaur, @Such_Saturation, @Travis, @Amazoniac, @Salmonamb, @Wagner83 et alia. Find interesting!
https://www.biorxiv.org/content/biorxiv/early/2017/10/19/205559.full.pdf
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