Stress during pubertal development affects female sociosexual behavior in mice.

Nitric Oxide Synthase Type I; Nos1 protein, mouse; Nitric Oxide Donors; Animals; Female; Male; Mice; Neurons/metabolism; Ventromedial Hypothalamic Nucleus/metabolism; Cues; Mice, Inbred C57BL; Smell/physiology; Nitric Oxide Donors/pharmacology; Sexual Behavior, Animal/physiology; Nitric Oxide Synthase Type I/metabolism; Nitric Oxide Synthase Type I/genetics; Sexual Maturation; Stress, Psychological/physiopathology; Neurons; Sexual Behavior, Animal; Smell; Stress, Psychological; Ventromedial Hypothalamic Nucleus; Chemistry (all); Biochemistry, Genetics and Molecular Biology (all); Physics and Astronomy (all)

Abstract :

[en] Puberty is a crucial phase for the development of female sexual behavior. Growing evidence suggests that stress during this period may interfere with the development of sexual behavior. However, the neural circuits involved in this alteration remain elusive. Here, we demonstrated in mice that pubertal stress permanently disrupted sexual performance without affecting sexual preference. This was associated with a reduced expression and activation of neuronal nitric oxide synthase (nNOS) in the ventrolateral part of the ventromedial hypothalamus (VMHvl). Fiber photometry revealed that VMHvl nNOS neurons are strongly responsive to male olfactory cues with this activation being substantially reduced in pubertally stressed females. Finally, treatment with a NO donor partially restored sexual performance in pubertally stressed females. This study provides insights into the involvement of VMHvl nNOS in the processing of olfactory cues important for the expression of female sexual behavior. In addition, exposure to stress during puberty disrupts the integration of male olfactory cues leading to reduced sexual behavior.

Disciplines :

Neurosciences & behavior

Author, co-author :

Bentefour, Yassine ; Université de Liège - ULiège > GIGA > GIGA Neurosciences - Neuroendocrinology

Bakker, Julie ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie de la différenciation sexuelle du cerveau

Language :

English

Title :

Stress during pubertal development affects female sociosexual behavior in mice.

Publication date :

30 April 2024

Journal title :

Nature Communications

eISSN :

2041-1723

Publisher :

Nature Research, England

Volume :

Issue :

Pages :

3610

Peer reviewed :

Peer Reviewed verified by ORBi

Tags :

GIGA Cell Imaging Platform

Additional URL :

https://www.nature.com/articles/s41467-024-47300-w.pdf

Funders :

F.R.S.-FNRS - Fonds de la Recherche Scientifique
ULiège - University of Liège

Funding number :

University of Liège. Grant reference number: FRS-S-SS-20/27

Funding text :

This work was supported by research grants from the Fonds National de la Recherche Scientifique (FNRS; (J.0008.21) to J.B. and (1.B.035.21F) to Y.B.) and the University of Li\u00E8ge (FRS-S-SS-20/27) to J.B. Y.B. is a FNRS Charg\u00E9 de Recherches and J.B. is a FNRS research director. We thank Mike Baum and Jacques Balthazart for their comments on an earlier version of this manuscript.

Available on ORBi :

since 13 May 2024

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Bibliography

J.L. Shifren B.U. Monz P.A. Russo A. Segreti C.B. Johannes Sexual problems and distress in United States women Obstet. Gynecol. 2008 112 970 978 18978095 10.1097/AOG.0b013e3181898cdb
S.R. Davis Circulating androgen levels and self-reported sexual function in women JAMA 2005 294 91 1:CAS:528:DC%2BD2MXlvVKmt7o%3D 15998895 10.1001/jama.294.1.91
B. Turna et al. Women with low libido: correlation of decreased androgen levels with female sexual function index Int. J. Impot. Res. 2005 17 148 153 1:STN:280:DC%2BD2M7htlamuw%3D%3D 15592425 10.1038/sj.ijir.3901294
S. Wåhlin-Jacobsen et al. Is there a correlation between androgens and sexual desire in women? J. Sex Med. 2015 12 358 373 25475395 10.1111/jsm.12774
J.D. Blaustein N. Ismail M.K. Holder Review: Puberty as a time of remodeling the adult response to ovarian hormones J. Steroid Biochem. Mol. Biol. 2016 160 2 8 1:CAS:528:DC%2BC2MXovV2qt7Y%3D 26004504 10.1016/j.jsbmb.2015.05.007
K.B. Smith et al. Pubertal immune challenge suppresses the hypothalamic-pituitary-gonadal axis in male and female mice Brain Res. Bull. 2021 170 90 97 2021mpup.book...S 1:CAS:528:DC%2BB3MXot12iu74%3D 33571552 10.1016/j.brainresbull.2021.02.006
N. Ismail P. Garas J.D. Blaustein Long-term effects of pubertal stressors on female sexual receptivity and estrogen receptor-α expression in CD-1 female mice Horm. Behav. 2011 59 565 571 1:CAS:528:DC%2BC3MXltFygsb4%3D 21376052 3085923 10.1016/j.yhbeh.2011.02.010
R. Basson et al. Dehydroepiandrosterone and cortisol as markers of HPA axis dysregulation in women with low sexual desire Psychoneuroendocrinology 2019 104 259 268 1:CAS:528:DC%2BC1MXlvV2rt78%3D 30909007 7343293 10.1016/j.psyneuen.2019.03.001
C.L. Sisk D.L. Foster The neural basis of puberty and adolescence Nat. Neurosci. 2004 7 1040 1047 1:CAS:528:DC%2BD2cXnvVOnt78%3D 15452575 10.1038/nn1326
A. Waylen D. Wolke Sex ‘n’ drugs ‘n’ rock ‘n’ roll: the meaning and social consequences of pubertal timing Eur. J. Endocrinol. 2004 151 U151 U159 1:CAS:528:DC%2BD2cXhtFSht7nM 15554900 10.1530/eje.0.151u151
M.C. Manotas D.M. González C. Céspedes C. Forero A.P.R. Moreno Genetic and epigenetic control of puberty Sex Dev. 2022 16 1 10 1:CAS:528:DC%2BB38XhsFCltrY%3D 34649256 10.1159/000519039
L.C. Drickamer Acceleration of puberty in female mice by a urinary chemosignal from pregnant or lactating females: timing and duration of stimulation Dev. Psychobiol. 1984 17 451 455 1:STN:280:DyaL2M%2FgsVCjsg%3D%3D 6541167 10.1002/dev.420170503
J. Bakker S.I. Honda N. Harada J. Balthazart The aromatase knock-out mouse provides new evidence that estradiol is required during development in the female for the expression of sociosexual behaviors in adulthood J. Neurosci. 2002 22 9104 9112 1:CAS:528:DC%2BD38XosV2is7g%3D 12388618 6757696 10.1523/JNEUROSCI.22-20-09104.2002
O. Brock M.J. Baum J. Bakker The development of female sexual behavior requires prepubertal estradiol J. Neurosci. 2011 31 5574 5578 1:CAS:528:DC%2BC3MXltFGgsbo%3D 21490197 3085119 10.1523/JNEUROSCI.0209-11.2011
A.A. Gerall J.L. Dunlap S.E. Hendricks Effect of ovarian secretions on female behavioral potentiality in the rat J. Comp. Physiol. Psychol. 1973 82 449 465 1:CAS:528:DyaE3sXhsFGjs7g%3D 4735922 10.1037/h0034113
J. Kercmar S.A. Tobet G. Majdic Social isolation during puberty affects female sexual behavior in mice Front. Behav. Neurosci. 2014 8 337 25324747 4179611 10.3389/fnbeh.2014.00337
A.J. Grippo B.S. Cushing C.S. Carter Depression-like behavior and stressor-induced neuroendocrine activation in female prairie voles exposed to chronic social isolation Psychosom. Med. 2007 69 149 17289829 3006075 10.1097/PSY.0b013e31802f054b
M.G. Ruscio T.D. Sweeny A. Gomez K. Parker C.S. Carter Social environment alters central distribution of estrogen receptor-α in juvenile prairie voles Physiol. Behav. 2009 98 296 1:CAS:528:DC%2BD1MXps1Wgsrk%3D 19539635 2765375 10.1016/j.physbeh.2009.06.005
V. Hellier et al. Female sexual behavior in mice is controlled by kisspeptin neurons Nat. Commun. 2018 9 2018NatCo..9.400H 29374161 5786055 10.1038/s41467-017-02797-2
Y. Bentefour J. Bakker Kisspeptin signaling and nNOS neurons in the VMHvl modulate lordosis behavior but not mate preference in female mice Neuropharmacology 2021 198 108762 1:CAS:528:DC%2BB3MXhvFemu7rM 34437905 10.1016/j.neuropharm.2021.108762
M.S.B. Silva et al. Female sexual behavior is disrupted in a preclinical mouse model of PCOS via an attenuated hypothalamic nitric oxide pathway Proc. Natl Acad. Sci. USA 2022 119 1:CAS:528:DC%2BB38XitFWisLrL 35867816 9335209 10.1073/pnas.2203503119
J. Clarkson A.E. Herbison Postnatal development of kisspeptin neurons in mouse hypothalamus; sexual dimorphism and projections to gonadotropin-releasing hormone neurons Endocrinology 2006 147 5817 5825 1:CAS:528:DC%2BD28Xht1yqtrzJ 16959837 10.1210/en.2006-0787
O. Brock J. Bakker The two kisspeptin neuronal populations are differentially organized and activated by estradiol in mice Endocrinology 2013 154 2739 2749 1:CAS:528:DC%2BC3sXhtF2nurbL 23744640 10.1210/en.2013-1120
C. Rivier S. Rivest Effect of stress on the activity of the hypothalamic-pituitary-gonadal axis: peripheral and central mechanisms Biol. Reprod. 1991 45 523 532 1:CAS:528:DyaK3MXlvFyksr8%3D 1661182 10.1095/biolreprod45.4.523
R.D. Romeo R. Patel L. Pham V.M. So Adolescence and the ontogeny of the hormonal stress response in male and female rats and mice Neurosci. Biobehav. Rev. 2016 70 206 216 1:CAS:528:DC%2BC28Xpslyjs78%3D 27235079 5074876 10.1016/j.neubiorev.2016.05.020
C.M. McCormick I.Z. Mathews HPA function in adolescence: Role of sex hormones in its regulation and the enduring consequences of exposure to stressors Pharmacol. Biochem. Behav. 2007 86 220 233 1:CAS:528:DC%2BD2sXitFOgtbo%3D 16901532 10.1016/j.pbb.2006.07.012
E.J.M. van der Vegt J. van der Ende C. Kirschbaum F.C. Verhulst H. Tiemeier Early neglect and abuse predict diurnal cortisol patterns in adults Psychoneuroendocrinology 2009 34 660 669 19128884 10.1016/j.psyneuen.2008.11.004
L.L. Carpenter T.T. Shattuck A.R. Tyrka T.D. Geracioti L.H. Price Effect of childhood physical abuse on cortisol stress response Psychopharmacology (Berl) 2011 214 367 375 1:CAS:528:DC%2BC3cXhtFGgtrrO 20838776 10.1007/s00213-010-2007-4
S. Entringer R. Kumsta D.H. Hellhammer P.D. Wadhwa S. Wüst Prenatal exposure to maternal psychosocial stress and HPA axis regulation in young adults Horm. Behav. 2009 55 292 298 1:CAS:528:DC%2BD1MXhtlSltbc%3D 19084531 10.1016/j.yhbeh.2008.11.006
R. Basson L.A. Brotto A.J. Petkau F. Labrie Role of androgens in women’s sexual dysfunction Menopause 2010 17 962 971 20539247 10.1097/gme.0b013e3181d59765
H.S. Kamin D.A. Kertes Cortisol and DHEA in development and psychopathology Horm. Behav. 2017 89 69 85 1:CAS:528:DC%2BC2sXmsVyrsw%3D%3D 27979632 10.1016/j.yhbeh.2016.11.018
J. Bakker S. Pierman D. González-Martínez Effects of aromatase mutation (ArKO) on the sexual differentiation of kisspeptin neuronal numbers and their activation by same versus opposite sex urinary pheromones Horm. Behav. 2010 57 390 395 1:CAS:528:DC%2BC3cXktlertbc%3D 19945459 10.1016/j.yhbeh.2009.11.005
K. Takumi N. Iijima S. Higo H. Ozawa Immunohistochemical analysis of the colocalization of corticotropin-releasing hormone receptor and glucocorticoid receptor in kisspeptin neurons in the hypothalamus of female rats Neurosci. Lett. 2012 531 40 45 1:CAS:528:DC%2BC38XhsFymt7zJ 23069671 10.1016/j.neulet.2012.10.010
A.C. Trouillet et al. Deletion of neural estrogen receptor alpha induces sex differential effects on reproductive behavior in mice Commun. Biol. 2022 5 383 1:CAS:528:DC%2BB38Xht1ensrjM 35444217 9021208 10.1038/s42003-022-03324-w
K. Chachlaki et al. NOS1 mutations cause hypogonadotropic hypogonadism with sensory and cognitive deficits that can be reversed in infantile mice Sci. Transl. Med. 2022 14 1:CAS:528:DC%2BB38Xis1ymu7vI 36197968 7613826 10.1126/scitranslmed.abh2369
C.C. Cheung D.M. Kurrasch J.K. Liang H.A. Ingraham Genetic labeling of steroidogenic factor-1 (SF-1) neurons in mice reveals ventromedial nucleus of the hypothalamus (VMH) circuitry beginning at neurogenesis and development of a separate non-SF-1 neuronal cluster in the ventrolateral VMH J. Comp. Neurol. 2013 521 1268 1288 1:CAS:528:DC%2BC3sXjtFSjsb0%3D 22987798 4304766 10.1002/cne.23226
K. Chachlaki et al. Phenotyping of nNOS neurons in the postnatal and adult female mouse hypothalamus J. Comparative Neurol. 2017 525 3177 3189 1:CAS:528:DC%2BC2sXhtlGitr%2FF 10.1002/cne.24257
P. Sántha et al. Restraint stress in rats alters gene transcription and protein translation in the hippocampus Neurochem. Res. 2012 37 958 964 22219132 10.1007/s11064-011-0688-7
R. Molteni A.C. Rossetti E. Savino G. Racagni F. Calabrese Chronic mild stress modulates activity-dependent transcription of BDNF in rat hippocampal slices Neural Plast. 2016 2016 2592319 26881097 10.1155/2016/2592319
M.E. Paskitti B.J. McCreary J.P. Herman Stress regulation of adrenocorticosteroid receptor gene transcription and mRNA expression in rat hippocampus: time-course analysis Mol. Brain Res. 2000 80 142 152 1:CAS:528:DC%2BD3cXmtF2qsbs%3D 11038247 10.1016/S0169-328X(00)00121-2
B. Xu et al. Cortisol excess-mediated mitochondrial damage induced hippocampal neuronal apoptosis in mice following cold exposure Cells 2019 8 612 1:CAS:528:DC%2BB3cXjsFalt7k%3D 31216749 6627841 10.3390/cells8060612
H. Zhao H. Xu X. Xu D. Young Predatory stress induces hippocampal cell death by apoptosis in rats Neurosci. Lett. 2007 421 115 120 1:CAS:528:DC%2BD2sXmsFCnsLY%3D 17566656 10.1016/j.neulet.2007.04.084
C. Crochemore et al. Direct targeting of hippocampal neurons for apoptosis by glucocorticoids is reversible by mineralocorticoid receptor activation Mol. Psychiatry 2005 10 790 798 1:CAS:528:DC%2BD2MXmsFWmsbo%3D 15940303 10.1038/sj.mp.4001679
K. Hashikawa et al. Esr1+ cells in the ventromedial hypothalamus control female aggression Nat. Neurosci. 2017 20 1580 1590 1:CAS:528:DC%2BC2sXhsFSkurvN 28920934 5953764 10.1038/nn.4644
S. Inoue et al. Periodic remodeling in a neural circuit governs timing of female sexual behavior Cell 2019 179 1393 1408.e16 1:CAS:528:DC%2BC1MXitFymtrnM 31735496 7096331 10.1016/j.cell.2019.10.025
D.W. Wesson M. Keller Q. Douhard M.J. Baum J. Bakker Enhanced urinary odor discrimination in female aromatase knockout (ArKO) mice Horm. Behav. 2006 49 580 586 1:CAS:528:DC%2BD28XksVCqtbc%3D 16448653 2263132 10.1016/j.yhbeh.2005.12.013
P.J. Bonthuis J.K. Patteson E.F. Rissman Acquisition of sexual receptivity: roles of chromatin acetylation, estrogen receptor-α, and ovarian hormones Endocrinology 2011 152 3172 1:CAS:528:DC%2BC3MXhtVemt7fK 21652725 3138229 10.1210/en.2010-1001
R. Remedios et al. Social behaviour shapes hypothalamic neural ensemble representations of conspecific sex Nature 2017 550 388 392 2017Natur.550.388R 1:CAS:528:DC%2BC2sXhs12ltLvI 29052632 5674977 10.1038/nature23885
Pfaff, D. W. Estrogens and brain function. Estrogens Brain Funct. https://doi.org/10.1007/978-1-4613-8084-9 (1980).
B.S. Rubin R.J. Barfield Induction of estrous behavior in ovariectomized rats by sequential replacement of estrogen and progesterone to the ventromedial hypothalamus Neuroendocrinology 1983 37 218 224 1:CAS:528:DyaL3sXlsFansb4%3D 6621803 10.1159/000123546
L. Senst D. Baimoukhametova T.-L. Sterley J.S. Bains Sexually dimorphic neuronal responses to social isolation Elife 2016 5 e18726 27725087 5059136 10.7554/eLife.18726
T.R. Butler O.J. Ariwodola J.L. Weiner The impact of social isolation on HPA axis function, anxiety-like behaviors, and ethanol drinking Front. Integr. Neurosci. 2014 7 102 24427122 3877772 10.3389/fnint.2013.00102
A.J. Grippo et al. Social isolation induces behavioral and neuroendocrine disturbances relevant to depression in female and male prairie voles Psychoneuroendocrinology 2007 32 966 980 1:CAS:528:DC%2BD2sXhtlaksL7E 17825994 2174914 10.1016/j.psyneuen.2007.07.004
S.L. Byers M.V. Wiles S.L. Dunn R.A. Taft Mouse estrous cycle identification tool and images PLoS ONE 2012 7 35538 2012PLoSO..735538B 10.1371/journal.pone.0035538
V.N. Sherathiya M.D. Schaid J.L. Seiler G.C. Lopez T.N. Lerner GuPPy, a Python toolbox for the analysis of fiber photometry data Sci. Rep. 2021 11 1 9 2021NatSR.11..1S 10.1038/s41598-021-03626-9
C. Dalla K. Antoniou Z. Papadopoulou-Daifoti J. Balthazart J. Bakker Oestrogen-deficient female aromatase knockout (ArKO) mice exhibit depressive-like symptomatology Eur. J. Neurosci. 2004 20 217 228 1:STN:280:DC%2BD2czktlSqtA%3D%3D 15245494 10.1111/j.1460-9568.2004.03443.x
Y. Bentefour M. Bennis R. Garcia S.B. M’hamed Effects of paroxetine on PTSD-like symptoms in mice Psychopharmacology (Berl) 2015 232 2303 2312 1:CAS:528:DC%2BC2MXnsl2rtA%3D%3D 25585683 10.1007/s00213-014-3861-2
N.Z. Kara Y. Stukalin H. Einat Revisiting the validity of the mouse forced swim test: systematic review and meta-analysis of the effects of prototypic antidepressants Neurosci. Biobehav. Rev. 2018 84 1 11 1:CAS:528:DC%2BC2sXhvVWmsrbM 29128579 10.1016/j.neubiorev.2017.11.003
Paxinos, G. & Franklin, K. B. J. The Mouse Brain in Stereotaxic Coordinates 2nd edn (Academic Press, 2001).