Brief communicationFemale-soiled bedding induced Fos immunoreactivity in the ventral part of the premammillary nucleus (PMv) of the male mouse
Introduction
The ventral part of the premammillary nucleus (PMv) of the rodent is located in the ventral portion of the most posterior region of the hypothalamus 1, 2. Anatomical and physiological data suggested that the PMv of the rat has important functions including the regulation of aggressive behavior [3] and gonadotrophin secretion 4, 5, 6. To fulfill these functions, the PMv of the rat produces many kinds of neuropeptides such as substance P, vasoactive intestinal polypeptide, neurotensin, and corticotropin-releasing hormone [7]. The PMv has direct neuronal connections with several reproductive function-related brain regions: the medial preoptic nucleus, the bed nucleus of the stria terminalis, the ventromedial hypothalamic nucleus (VMH), and the posterodorsal part of the medial amygdaloid nucleus (MePD) [8]. In addition, the PMv has a large population of neurons with androgen receptors in the rat 9, 10, 11 and the Syrian hamster [38]. These facts strongly suggest that the PMv plays an important role in the initiation and/or expression of the mating behavior of male rodents.
According to many reports and articles, pheromone signals from estrous females can alter the physiological function, and initiate mating behavior, of the males 13, 14, 15. It is well established that male- and/or female-soiled bedding is useful as a source of sex-related pheromones. For example, Vandenbergh [16] reported that exposure to male-soiled bedding accelerates the onset of puberty in juvenile female mice. Keverne and de la Riva [17] showed that the frequency of pregnancy block increases when female mice are housed in cages that contain bedding soiled by alien male mice. Exposure to female-soiled bedding induces the expression of Fos immunoreactivity (Fos-ir) [18], and increases the size of the synapses [19], in the accessory olfactory bulb in the mice and rat, respectively.
Mice provide important and useful models for studies of pheromone-inducible reproductive behaviors 20, 21, 22. However, the action of female pheromones on the hypothalamus of the male mouse has not been reported. Although its physiological function is still unclear, the PMv may be involved in initiating male mating behavior by receiving sex pheromone-related neural activities. Therefore, we have examined whether the number of Fos-positive cells within the PMv of the male mouse increases following exposure to female-soiled bedding.
Examination of the medial preoptic area and the bed nucleus of the stria terminalis, which form the so-called “classical” chemosensory pathway, was beyond the scope of the present study.
Section snippets
Animal treatments and tissue preparation
Sexually inexperienced 7- to 8-week-old ICR strain male and female mice (CREA Japan Inc., Tokyo, Japan) were studied. All of the animals were housed (four to five animals/cage, male and female separately) in standard laboratory cages (27 × 16 × 14 cm) with wood-chip bedding on the floor, and were provided with food and water ad lib. They were housed in an air-conditioned room (24°C) with a controlled light–dark cycle (12-h light/12-h dark).
For approximately 48 h before the experiment began, the
Results
Fos-ir was clearly greater in throughout the PMv region of the male mice that had been exposed to the female mice-soiled bedding compared to the controls (Fig. 1B vs. 1C). Exposure to the soiled bedding elicited Fos-ir in the male PMv that was significantly greater than that seen in mice exposed to clean bedding (Fig. 3; clean versus soiled = 12.2 ± 7.9 vs. 380.3 ± 60.3 cells, p < 0.05). However, Fos-ir levels in the MePD (clean versus soiled = 16.3 ± 2.0 vs. 20.1 ± 3.2 cells) and in the PMCo
Discussion
In this study, we observed that exposure to female-soiled bedding increased Fos-ir in the PMv, but not in the VMH, MePD, and PMCo, of the male mouse. It has been reported that male-soiled bedding and/or male urine increase c-fos mRNA expression and/or Fos-ir in the main and accessory olfactory bulbs of the female 18, 24. However, to our knowledge, there has been no report of altered c-fos mRNA expression and/or Fos-ir in the male's hypothalamic area in response to pheromones from the female.
Acknowledgments
This work was supported in part by CREST of Japan Science and Technology Corporation to M. Ichikawa, by a Research Fellowship of the Japan Society for the Promotion of Science to M.M., and by a Grant-in Aid for the Encouragement of Young Scientists from The Ministry of Education, Science, Sports and Culture of Japan to M.Y. (910740391).
References (38)
- et al.
Colocalization of neuronal nitric oxide synthase and androgen receptor immunoreactivity in the premammillary nucleus in rats
Neurosci Res
(1996) - et al.
Co-localization of androgen receptor and nitric oxide synthase in the ventral premammillary nucleus of the newborn ratan immunohistochemical study
Dev Brain Res
(1997) Chemical signals and reproductive behavior
- et al.
Testosterone augments neuronal fos responses to estrous odors throughout the vomeronasal projection pathway of gonadectomized male and female rats
Horm Behav
(1998) Pheromonal regulation of puberty
- et al.
Molecular aspects of pheromonal communication via the vomeronasal organ of mammals
Trends Neurosci
(1998) - et al.
Neural substrates for leptin and neuropeptide y (npy) interactionhypothalamic sites associated with inhibition of NPY-induced food intake
Physiol Behav
(1998) - et al.
Mating and agonistic behavior produce different patterns of Fos immunolabeling in the male Syrian hamster brain
Neuroscience
(1995) - et al.
c-fos immunoreactivity in the sexually dimorphic area of the hypothalamus and related brain regions of male gerbils after exposure to sex-related stimuli or performance of specific sexual behaviors
Neuroscience
(1996) - et al.
Stimulation of male and female sexual behavior in gonadectomized rats with estrogen and androgen therapy and its inhibition with concurrent anti-hormone therapy
Physiol Behav
(1975)
Ventromedial hypothalamic control of food intake and satietya reappraisal
Brain Res
Concomitant regulation of running activity and metabolic change by the ventromedial nucleus of the hypothalamus
Brain Res
Synaptic reorganization in the medial amygdaloid nucleus after lesion of the accessory olfactory bulb of adult rat. I. Quantitative and electron microscopic study of the recovery of synaptic density
Brain Res
The Rat Brain in Stereotaxic Coordinates
Atlas of the Mouse Brain and Spinal Cord
The neucleus premammillaris ventralis (pmv) and aggressive behavior in the rat
Aggress Behav
Beta-adrenergic receptors in the premammillary nucleus mediate the inhibition on LH release evoked by locus ceruleus stimulation
Neuroendocrinology
Ventral premammillary nuclei mediate pheromonal-induced LH release stimuli in the rat
Neuroendocrinology
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Male Sexual Behavior
2017, Hormones, Brain and Behavior: Third EditionThe hypothalamic ventral premammillary nucleus: A key site in leptin's regulation of reproduction
2014, Journal of Chemical NeuroanatomyDistribution of the neuronal inputs to the ventral premammillary nucleus of male and female rats
2014, Brain ResearchCitation Excerpt :In fact, conspecific opposite sex odors alone induce Fos expression in PMV neurons of rodents. These neurons coexpress nitric oxide synthases and cocaine- and amphetamine-regulated transcript (CART) (Cavalcante et al., 2006a; Donato et al., 2010; Yokosuka et al., 1999). We further demonstrated that CART mRNA is increased in the PMV of males following exposure to female odors and that PMV CART neurons project to areas controlling gonadotropin releasing hormone (GnRH) secretion (Cavalcante et al., 2006a; Rondini et al., 2004).
Chemosignals and hormones in the neural control of mammalian sexual behavior
2013, Frontiers in NeuroendocrinologyCitation Excerpt :At the very least, the PMCo, a steroid-sensitive structure, appears to regulate responses to opposite sex odors as PMCo lesions in female rats eliminate preference for sexually-active male’s odor (Romero et al., 1990) and alters the pattern of chemoinvestigation in male hamsters (Maras and Petrulis, 2008). Similarly, the PVH is a highly steroid-sensitive structure that responds to opposite-sex odors (Donato et al., 2010; Yokosuka et al., 1999) but little is known about its role in reproductive behavior. What data exists suggests that the PVH may be very important for appetitive aspects of male sexual behavior.
Discrete melanocortin-sensitive neuroanatomical pathway linking the ventral premmamillary nucleus to the paraventricular hypothalamus
2013, NeuroscienceCitation Excerpt :DAB-labeled sections were mounted on gelatin-coated slides, air-dried, dehydrated in graded ethanols, cleared in xylenes, and coverslipped with Permaslip (Alban Scientific). The PMv neurons are engaged in conspecific odors responses (Kollack-Walker and Newman, 1995; Yokosuka et al., 1999; Veening et al., 2005; Cavalcante et al., 2006; Donato et al., 2010). Thus, we designed experiments to assess whether MC4-R-GFP neurons in the PMv respond to these stimuli.
Male and female odors induce Fos expression in chemically defined neuronal population
2010, Physiology and BehaviorCitation Excerpt :Recently, we showed that MEA neurons expressing Ucn 3 densely innervate the PMV [12]. It is noteworthy that PMV neurons of male rodents also express Fos immunoreactivity (Fos-ir) in response to female odors or sexual/aggressive behaviors [18,27,28]. The functional relationship between MEA and PMV is still unsettled.
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Research Fellow of the Japan Society for the Promotion of Science.