Ontogeny of the sexually dimorphic nucleus of the preoptic area

An area of increased cell density in the medial preoptic area of the adult rat brain which is markedly larger in volume in the male has been named the Sexually Dimorphic Nucleus of the Preoptic Area (SDN-POA). It has been further shown that the presence of the testes or exogenous androgen during the first week of postnatal life significantly increases the volume of the SDN-POA in the brain of the adult. The present study was conducted to describe the time course of the prenatal and postnatal development of the SDN-POA in the intact male and female rat. Sprague-Dawley females were housed with males on proestrus. The presence of sperm in the vaginal smear on estrus was used to define day 1 of gestation. Male and female prenatal and postnatal pups were sacrificed and perfused with 10% neutral formalin on days 20, 21, 22, 23, 24, 25, 26, 27, 28, 30, and 32 postfertilization. Following histological sectioning at 60 m?m and staining with thionin, three investigators independently drew the boundaries of the SDN-POA on successive sections, using a microprojector at a magnification of 43.5. A fourth investigator averaged the three drawings; from this average, the nuclear volume was determined with a calibrated planimeter. All drawings and measurements were performed without knowledge of age or sex since the brains were coded according to a random number generator. The volume of the SDN-POA was found to be significantly larger in males than in females on days 23, and 25 through 32. Moreover, the volume of the SDN-POA increased significantly with age in the male, but there was no change in SDN-POA volume in the female. In order to test the specificity of the sexual dimorphism of the SDN-POA, five different linear measurements were taken of brain size. There was a significant increase in these parameters in both sexes with increasing age; however, there was no significant sex difference found. Thus, the sex difference in volume of the SDN-POA cannot be accounted for by sex differences or age-related changes in brain size per se. These data suggest that the development of the SDN-POA (as measured by volume) is itself sexually dimorphic. There are dramatic increases in the male, but not in the female, during a time-period which is known to be critical for sexual differentiation of the brain.     

Steroid autoradiography of the sexually dimorphic nucleus of the preoptic area

Autoradiography was performed to determine if the neurons of the sexually dimorphic nucleus of the preoptic area (SDN-POA) in the adult rat accumulate estradiol (E2), testosterone (T), and/or dihydrotestosterone (DHT). Three days prior to steroid administration, adult male and female Sprague-Dawley rats were gonadectomized and adrenalectomized. Animals were then given either [3H]T, [3H]E2, or [3H]DHT through an indwelling jugular cannula. One hour later, animals were decapitated and brain sections processed for thaw mount autoradiography. The autoradiograms which contained the SDN-POA and an adjacent area of the medial preoptic area (MPOA) were quantitatively analyzed using the 3 times background, 5 times background, and Poisson criteria for labeled cells. In general, cells in the SDN-POA and the MPOA accumulate T, E2, or DHT. For both sexes, there is a greater percentage of labeled cells in the SDN-POA than in the MPOA, and a greater percentage of labeled cells following E2 exposure than following T or DHT exposure. In addition, there is a sex difference (male greater than female) in the percentage of labeled cells following T exposure. In summary, these data indicate that adult SDN-POA neurons do accumulate gonadal steroids.     

Evidence for the existence of a sexually dimorphic nucleus in the preoptic area of the rat

The volume of an intensely staining component of the preoptic area of the male rat is markedly larger than that of the female. Moreover, its volume in both sexes is altered by perinatal hormone exposure consistent with the view that this brain region undergoes hormone dependent sexual differentiation. The present study was carried out to determine if this sexually dimorphic area of the brain has a greater cell density than that of the surround, and if a unique population or distribution of cells, either within one sex or between males and females, characterized this region. A single coronal paraffin section (10 m?m) through the approximate center of this sexually dimorphic area in four adult gonadectomized rats of each sex was evaluated systematically. Each cell was labelled as being inside or outside of the sexually dimorphic area. In addition to cell density per unit area the following parameters were evaluated through a closed circuit video system: cell size, staining intensity, shape, and the presence of processes and of a nucleolus. The presence of a nucleolus was further used to identify neurons within the total population of almost 5000 cells that was evaluated. In both sexes, the sexually dimorphic area was characterized by a significantly increased cell density per unit area compared to that of the surround. On this basis, the term, the Sexually Dimorphic Nucleus of the Preoptic Area (SDN-POA) is proposed, for this region. Moreover, the SDN-POA of the male was characterized by increased neuronal density per unit area. The SDN-POA in the male was also found to contain larger cells and neurons, as determined by direct measurement of their greatest diameter, as well as a greater percentage of cells and neurons rated large on a three-point scale (small, medium, and large). No consistent differences in frequency distribution by stain intensity, shape, or the presence of cell processes were found to characterize the SDN-POA or contribute to the sexual dimorphism. It is concluded that the marked sex difference in the volume of the SDN-POA is due principally to an increase in the male of the total area of higher cell and neuronal density. However, the present results do not eliminate the possibility that more subtle differences in neuronal characteristics may exist in the SDN-POA.     

Sex difference in dendritic development of the sexually dimorphic nucleus of the preoptic area in the rat

Sex differences in the growth and dendritic development of neurons in the sexually dimorphic nucleus of the preoptic area were examined with quantitative Golgi techniques during early postnatal life in rats. Neuronal size and dendritic extent were found to increase more in males than in females during the first 10 postnatal days, while the numbers of primary and terminal dendrites were similar in the two sexes. The onset of greater dendritic growth in males occurs just after the volume of the nucleus begins to exhibit sexual dimorphism, between 24 and 26 days after fertilization. Growth of dendrites in this region may be related to the presence of sex hormones during the critical period of sexual brain differentiation.     

Simultaneous catecholamine histofluorescence and thymidine autoradiography of the sexually dimorphic nucleus of the preoptic area in the rat

The sexually dimorphic nucleus of the preoptic area (SDN-POA) in the rat represents a morphological substrate in which the influence of gonadal hormones on the process of sexual differentiation of the brain can be seen. Since the medial preoptic area (MPO) is a region rich in catecholamine (CA) terminals, it is possible that catecholamines may play a role either in the differentiation of the perinatal SDN-POA or in the function of this nucleus in the adult. It is not known whether catecholamine terminals exist within the SDN-POA or whether they can directly influence the activity of SDN-POA neurons. The present study was conducted to determine the extent to which catecholamines innervate this nucleus and further to elucidate the possibility of a potential sexual dimorphism in the innervation pattern. In order to determine which of the neurons in the MPO are within the SDN-POA we have utilized the fact that the SDN-POA has a prolonged period of neurogenesis in comparison to other neurons of the MPO. Thus, tritiated thymidine-labeled neurons can be used as a detection criterion for the SDN-POA. To conduct this experiment, timed pregnant Sprague-Dawley females were given a single injection of [3H]thymidine on Day 18 of gestation. Pups were killed as adults and prepared for fluorescence histochemistry of monoamines. Sections adjacent to those examined for catecholamine fluorescence were treated for autoradiographic localization of [3H]thymidine. Fluorescence innervation patterns were plotted within the boundaries of the nucleus following its identification from Nissl sections as well as from adjacent autoradiograms simultaneously viewed in a comparator bridge microscope with dark-field illumination.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ontogeny of a sexually dimorphic opioid system in the preoptic area of the rat

A striking sexual dimorphism exists in the distribution of Met-enkephalin (m-ENK) immunoreactive fibers in the preoptic area of the rat brain. A dense plexus of m-ENK fibers, approximately 100 microns wide, is present in the periventricular part of the preoptic area (pePOA) in adult females, but not in males. In the present study, we have examined the time of first expression of this female-typical system during the course of normal brain development. The female-typical plexus of m-ENK fibers in the pePOA is not expressed prepubertally, but first becomes evident during the late peri-pubertal period (usually by 40 days of age). In adult females, the maintenance of immunohistochemically detectable levels of m-ENK in this fiber system is dependent upon the presence of gonadal steroids, especially estradiol. Therefore, we examined whether exposure of pre-pubertal females to estradiol would result in precocious expression of the m-ENK fiber plexus. The results of this experiment demonstrate that exposure to estradiol for 7 days induces the full expression of the m-ENK fiber system in the pePOA of prepubertal females, such that it was indistinguishable from that seen in mature animals. These results demonstrate that while the sexually dimorphic m-ENK system of the pePOA is not normally expressed prepubertally, the neural substrate is nevertheless in place and capable of being activated by exposure to exogenous estradiol.     

Development of the sexually dimorphic nucleus of the preoptic area and the influence of estrogen-like compounds

One of the wel -defined sexual y dimorphic structures in the brain is the sexual y dimorphic nucleus, a cluster of cells located in the preoptic area of the hypothalamus. The rodent sexual y dimorphic ...     

Implication of testosterone metabolism in the control of the sexually dimorphic nucleus of the quail preoptic area

In quail, testosterone (T) activates male copulation and affects the volume and cytoarchitectonic organization of the medial preoptic nucleus (POM). T metabolism (especially its aromatization) is critical for the production of these behavioral effects. We wondered whether T metabolism is also playing a role in the induction of the morphological changes in POM. We compared the effects of T and of its metabolites in this nucleus. To obtain an independent evaluation of the role played by aromatase, morphological effects of T associated or not with the aromatase inhibitor R76713 were also assessed. As previously observed, T increased the POM volume and the cross-sectional area of the neurons in the lateral part of the nucleus. The effects of T on the neurons in the lateral POM were mimicked in part by the combined treatment with estradiol and 5α-dihydrotestosterone. They were also blocked by the aromatase inhibitor. This suggests that T aromatization plays a critical role in the mediation of the cytoarchitectonic effects of T. A specific role for androgens alone remains to be established.     

Intrauterine proximity to male fetuses affects the morphology of the sexually dimorphic nucleus of the preoptic area in the adult rat brain

Previous studies on polytocous rodents have revealed that the fetal intrauterine position influences its later anatomy, physiology, reproductive performance and behavior. To investigate whether the position of a fetus in the uterus modifies the development of the brain, we examined whether the structure of the sexually dimorphic nucleus of the preoptic area (SDN-POA) of rat brains accorded to their intrauterine positions. Brain sections of adult rats gestated between two male fetuses (2M) and between two female fetuses (2F) in the uterus were analysed for their immunoreactivity to calbindin-D28k, which is a marker of the SDN-POA. The SDN-POA volume of the 2M adult males was greater than that of the 2F adult males, whereas the SDN-POA volume of the 2M and 2F adult females showed no significant difference. This result indicated that contiguous male fetuses have a masculinizing effect on the SDN-POA volume of the male. To further examine whether the increment of SDN-POA volume in adulthood was due to exposure to elevated steroid hormones during fetal life, concentrations of testosterone and 17beta-estradiol in the brain were measured with 2M and 2F fetuses during gestation, respectively. On gestation day 21, the concentrations of testosterone and 17beta-estradiol in the brain were significantly higher in the 2M male rats as compared with the 2F male rats. The results suggested that there was a relationship between the fetal intrauterine position, hormone transfer from adjacent fetuses and the SDN-POA volume in adult rat brains.     

Sexual differentiation of the human hypothalamus: ontogeny of the sexually dimorphic nucleus of the preoptic area

Sexual differentiation of the hypothalamus of the human brain is generally believed to take place around midpregnancy and thought to be related to the development of sexual orientation and gender identity. The present life span study on the human sexually dimorphic nucleus (SDN) of more than a hundred subjects revealed, however, that at the age of 2-4 years the SDN cell number reaches a peak value, and that only after this age sexual differentiation becomes manifest. Furthermore, the SDN cell number in homosexual men was not different from that of the male reference group, but significantly larger than the cell number in age-matched women.     

Cholecystokinin synapses in the sexually dimorphic central part of the medial preoptic nucleus

The distribution of immunoreactive cholecystokinin synapses in the medial preoptic nucleus was studied. At the light microscopic level, the relative density of cholecystokinin in the nucleus corresponds to its three subdivisions. The sexually dimorphic central part of the nucleus was filled with a very dense plexus of cholecystokinin fibers/terminals. At the ultrastructural level, cholecystokinin-positive boutons contained labeled, dense core vesicles and clear vesicles as well as a population of unlabeled vesicles. The cholecystokinin boutons formed axodendritic, axosomatic, and axoaxonic interactions. Very few of the boutons were found in apposition with unlabeled elements but without any evidence of contact, i.e., synaptoid-type. Interestingly, cholecystokinin-positive, dendrite-like structures occasionally extended thin processes that were observed to end in a bouton containing both light and dense core vesicles. These varicosities were observed to have synaptoid endings. The dense innervation and synaptoid interaction of cholecystokinin elements in the central part of the medial preoptic nucleus may help to clarify the peptide's function in the medial preoptic area.     

Perinatal androgenization prevents age-related neuron loss in the sexually dimorphic nucleus of the preoptic area in female rats

To investigate the effect of perinatal testosterone exposure, which simulates the endogenous testosterone peak, on neuron loss during aging, nuclear morphology was evaluated in male and female rats as well as in female rats treated with testosterone perinatally followed by ovariectomy (TE/Ovx). Additionally, neuronal apoptosis, which occurred primarily at postnatal day 8 (PND8), was identified by in situ TUNEL staining. Neuronal density, nuclear volume, total neuronal number and pyknotic ratio were estimated after HE stain at PND8, middle age and old age. The results showed that age-related decrease in neuronal nuclear volume and total neuron number in the sexually dimorphic nucleus of the preoptic area (SDN-POA) of female rats was significantly diminished by TE/Ovx. The pyknotic ratio in the SDN-POA of female rats at PND8 was significantly higher than that of males, and neuronal death was reversed by testosterone exposure, while no significant difference of pyknotic ratios was observed among male, female and TE/Ovx female rats at both middle and old age. Moreover, the high apoptotic incidence of female rats at PND8 was significantly diminished by testosterone exposure. These results suggest that neuron loss in the SDN-POA during aging may be predominantly determined by perinatal testosterone through modulation of postnatal neuronal apoptosis.     

Neurogenesis of motoneurons in the sexually dimorphic spinal nucleus of the bulbocavernosus in rats

The spinal nucleus of the bulbocavernosus (SNB) consists of motoneurons innervating striated perineal muscles in male rats. The adult number of SNB motoneurons can be increased or decreased by perinatal manipulations with androgen or anti-androgen. The present results with thymidine autoradiography demonstrate that SNB motoneurons undergo their final mitosis on the fourteenth day of gestation. Because testosterone production in male rats does not begin until after gestational day 14, androgens are unlikely to affect SNB neurogenesis in normal males. By extension, hormonal manipulations more than a week later, which affect the number of SNB cells, are probably mediated by alterations in the death or specification of cells, but not their proliferation.     

Ontogeny of a sexually dimorphic nucleus in the preoptic area of the Japanese quail (Coturnix japonica).

The nucleus preopticus medianus (POMn) is a sexually dimorphic nucleus in Japanese quail (Coturnix japonica) that is critically involved in the hormonal activation of male copulatory behavior. The larger volume apparent in males appears to depend upon circulating testosterone [Brain Res., 416 (1987) 59-68; J. Comp. Neurol., 303 (1991) 443-456]. The present study determined when during normal development this nucleus becomes dimorphic. POMn and a control nucleus, the nucleus commissurae pallii (nCPa), were traced from Nissl-stained coronal sections (40 microns) from animals sacrificed at 2, 3, 4, 5, 6 or 7 weeks of age. Areas were measured and used to calculate volume. POMn volumes were not significantly different in males and females through 5 weeks of age. The dimorphism in POMn volume then became apparent at 6 weeks of age as a function of an increase in male POMn volume between 5 and 6 weeks of age. No significant differences were apparent at any developmental age in nCPa volume. The appearance of a sexual dimorphism in POMn volume is coincident with the pubertal surge in testosterone that occurs between 5 and 6 weeks of age [Horm. Behav., 11 (1978) 175-182], and is also coincident with behavioral sexual maturity.     

Photoperiod affects the morphology of a sexually dimorphic nucleus within the preoptic area of male Japanese quail

Changes in the gross and cellular morphology of the nucleus preopticus medianus (POMn) were measured in response to changes in photoperiod in adult male Japanese quail (Coturnix japonica). POMn volume and the soma size of a dorsolateral population of neurons within POMn decreased when birds were moved from long day housing conditions (16L,8D) to short day housing conditions (8L,16D), and then increased again when birds were moved back to long day conditions, presumably as a function of the changes in circulating testosterone that accompanied changing daylengths. Male Japanese quail exhibit sexual behavior only when housed under long day housing conditions that approximate the photoperiod of the spring/summer breeding season, and do not exhibit sexual behavior when housed under short day conditions characteristic of fall/winter. Because POMn is known to be critically involved in the expression of male copulatory behavior, these morphological changes in the adult brain likely represent key functional events associated with the seasonal regulation of sexual behavior in male Japanese quail.     

Effects of prenatal stress on differentiation of the sexually dimorphic nucleus of the preoptic area (SDN-POA) of the rat brain

The present study was designed to determine the effects of prenatal malnutrition or environmental stress on the development of the sexually dimorphic nucleus of the preoptic area (SDN-POA). Pregnant rats were divided into a control group and two treatment groups (immobilization-illumination-heat or environmental stress, and nutritional stress). The two forms of stress were administered during the third trimester of gestation (days 14-20). Male and female offspring were sacrificed at birth, 20, and 60 days postnatally. The cross-sectional area of the SDN-POA was identified under light microscopy and was measured. The data confirm previous studies by showing a significant sex difference in the SDN-POA between control male and female rats. Prenatally stressed males sacrificed 20 and 60 days after birth showed SDN-POA areas 50% smaller than the nuclear areas of control males. The size of the SDN-POA of female offspring, however, was not significantly altered by prenatal treatments.     

Evidence that serotonin is involved in the sexually dimorphic development of the preoptic area in the rat brain

To investigate the possibility that serotonin plays a role in the sexually dimorphic development of a nucleus in the medial preoptic area of the rat brain, p-chlorophenylalanine, an inhibitor of serotonin biosynthesis, was administered to pregnant dams from day 8 of gestation until parturition. This treatment did not alter plasma steroid levels but increased the volume of the sexually dimorphic nucleus in female neonates to that of control males. Thus, serotonin is implicated as a neurochemical which may be involved in the sexually dimorphic development of the preoptic area.     

The cells of origin of a sexually dimorphic serotonergic input to the medial preoptic nucleus of the rat

The medial preoptic nucleus (MPN) is a sexually dimorphic complex composed of 3 distinct cytoarchitectonic subdivisions, and a sexually dimorphic distribution of presumably serotonergic fibers is associated with the lateral part of the nucleus (MPNl). In this study the probable cells of origin for these serotonergic fibers were identified by using a combined fluorescent retrograde tracer and immunofluorescence method. Serotonergic afferents to the MPN appear to arise exclusively from the dorsal raphe nucleus (B7), the median raphe nucleus (B8), and the region adjacent to the medial lemniscus (B9).