Kunwar P. Bhatnagar

Structure and diversity in mammalian accessory olfactory bulb

The accessory olfactory bulb (AOB) is the first neural integrative center for the olfactory‐like vomeronasal sensory system. In this article, we first briefly present an overview of vomeronasal system organization and review the history of the discovery of mammalian AOB. Next, we briefly review the evolution of the vomeronasal system in vertebrates, in particular the reptiles. Following these introductory aspects, the structure of the rodent AOB, as typical of the well‐developed mammalian AOB, is presented, detailing laminar organization and cell types as well as aspects of the homology with the main olfactory bulb. Then, the evolutionary origin and diversity of the AOB in mammalian orders and species is discussed, describing structural, phylogenetic, and species‐specific variation in the AOB location, shape, and size and morphologic differentiation and development. The AOB is believed to be absent in fishes but present in terrestrial tetrapods including amphibians; among the reptiles AOB is absent in crocodiles, present in turtles, snakes, and some lizards where it may be as large or larger than the main bulb. The AOB is absent in bird and in the aquatic mammals (whales, porpoises, manatees). Among other mammals, AOB is present in the monotremes and marsupials, edentates, and in the majority of the placental mammals like carnivores, herbivores, as well as rodents and lagomorphs. Most bat species do not have an AOB and among those where one is found, it shows marked variation in size and morphologic development. Among insectivores and primates, AOB shows marked variation in occurrence, size, and morphologic development. It is small in shrews and moles, large in hedgehogs and prosimians; AOB continues to persist in New World monkeys but is not found in the adults of the higher primates such as the Old World monkeys, apes, and humans. In many species where AOB is absent in the adult, it often develops in the embryo and fetus but regresses in later stages of development. Finally, new areas in vomeronasal system research such as the diversity of receptor molecules and the regional variation in receptor neuron type as well as in the output neurons of the AOB and their projection pathways are briefly discussed. In view of the pronounced diversity of size, morphologic differentiation, and phylogenetic development, the need to explore new functions for the vomeronasal system in areas other than sexual and reproductive behaviors is emphasized. Microsc. Res. Tech. 43:476–499, 1998.

Female genital anomalies affecting reproduction

OBJECTIVE A multitude of female congenital anomalies are uncommon. However, their impact on reproduction can be profound. The aim of this review is to remind the practicing physician of the clinically relevant embryology and summarize the studies that look at the impact of such various anomalies on a womans fecundity. We review particular surgical therapies that possibly may improve fertility in such women. DESIGN Review and critique of available studies in which particular surgical therapies were done and whether they truly improved fertility in these women with congenital reproductive anomalies. RESULTS Clear evidence demonstrates that uterine septum resection is effective in women with demonstrated recurrent pregnancy losses. Arcuate uterus has little impact on reproduction. Other studies fail to definitively show that surgical correction will improve pregnancy retention or fertility except for specifically indicated clinical scenarios. CONCLUSIONS The practicing reproductive specialist should have working knowledge of evidence-based therapeutic options for women with reproductive congenital anomalies. A summary chart has been devised to clearly associate embryologic structures with normal adult derivative as well as anomalous structures.

Human Olfactory Bulb: Aging of Glomeruli and Mitral Cells and a Search for the Accessory Olfactory Bulba

ABSTRACT: The aims of this study on the human olfactory bulb were two. First morphometry of the bulbs revealed marked declines during aging in the numbers of mitral cells and glomeruli, the bulbs principal integrative and relay elements. Numbers of glomeruli and mitral cells in each bulb of the young adult human were found to be approximately 8,000 and 40,000, respectively; these numbers declined steadily with age at an approximate rate of 10% per decade, so that in the ninth and tenth decades less than 30% of these elements remain in place. Such a marked decline with aging is suggested to underlie in part the decline in olfactory abilities (odor detection and identification) of humans with aging. In a separate study a systematic search for presence of an accessory olfactory bulb in the adult and aging bulbs was undertaken. No positive evidence for such an organized formation was found in the various regions of the adult bulbs of different age groups. The implications of these negative findings for the recent theories on human vomeronasal function and pheromonal perception are discussed.

VOMERONASAL ORGAN IN BATS AND PRIMATES : EXTREMES OF STRUCTURAL VARIABILITY AND ITS PHYLOGENETIC IMPLICATIONS

The mere appearance of a tubular, epithelially‐covered, bilateral structure, no matter how minuscule, on the anteroventral nasal septum of tetrapods, is generally called the vomeronasal organ (of Jacobson). However, considering the functionality of this chemosensory structure, the presence of a non‐cilated (microvillar) neuroepithelium (and not just any odd type of epithelium) encased in a variously shaped vomeronasal cartilage, along with vomeronasal nerve bundles and above all an accessory olfactory bulb connected to the limbic vomeronasal amygdala, are the absolute essential neurostructural characteristics and anatomic requirement for a functional VNO and the accessory olfactory system in any tetrapod. The distribution of the vomeronasal organ is reported here in two mammalian orders: Chiroptera and Primates. An impressive data pool on the vomeronasal organ of bats is now available, pointing to the fact that at this time bats may be the only group in which this organ system is extremely variable, ranging from total absence (even in the embryo) to spectacular development with numerous intervening stages in different chiropteran species. Of the eighteen bat families, only one family of New World leaf‐nosed bats, family Phyllostomidae, exhibits functional vomeronasal organs. The vespertilionid bat Miniopterus, and the mormoopid bat Pteronotus, present exceptions to this rule. Among Primates, very few species have been rigorously studied. As a result, developmental variability of the vomeronasal organ is almost unknown; either the vomeronasal organ is well developed (such as in New World monkeys) or absent (as in Old World monkeys and great apes) in the adult. The concept whether adult humans or embryonic and fetal forms are endowed with this so‐called sixth sense, is a controversial one and is under intense study in our laboratory and by others. The general phylogenetic implications based on our cladistic analysis of bats are that the vomeronasal organ complex has evolved several times. Among the prosimians and platyrrhine primates, the organ is well developed, although to a varying degree. Among catarrhine primates, its loss has occurred only once, as it is generally absent in the adult forms. Microsc. Res. Tech. 43:465–475, 1998.

Reappraisal of the Vomeronasal System of Catarrhine Primates: Ontogeny, Morphology, Functionality, and Persisting Questions

The vomeronasal organ (VNO) is a chemosensory organ that functions in sociosexual communication in many vertebrates. In strepsirhine primates and New World monkeys, the bilateral VNOs are traditionally understood to exist as a well‐developed chemosensory epithelial unit. In contrast, the VNOs of catarrhine primates are thought to be absent or exist only as reduced epithelial tubes of uncertain function. However, the VNO of New World monkeys shows substantial variation in the extent of sensory epithelium. Recent findings that the chimpanzee (Pan troglodytes) possesses a VNO similar to humans suggest the variability of the VNO among haplorhine primates may be more extensive than previously thought, and perhaps more at par with that observed in chiropterans. The atypical histologic structure and location of the human/chimpanzee VNO suggest accessory glandular secretion and transport functions. Other catarrhine primates (e.g., Macaca spp.), may truly be characterized by VNO absence. Unique aspects of facial growth and development in catarrhine primates may influence the position or even presence of the VNO in adults. These recent findings demonstrate that previous investigations on some catarrhine primates may have missed the VNO and underestimated the extent of variability. As an understanding of this variation increases, our view of VNO functionality and associated terminology is changing. Further investigations are needed to consider phylogenetic implications of VNO variability and the association of craniofacial form and VNO anatomic position in primates. Anat Rec (New Anat) 265:176–192, 2001.

Melatonin and human reproduction: Shedding light on the darkness hormone

Melatonin, N-acetyl-5-methoxytryptamine, is a molecule with diverse physiological functions. This neuro-hormone affects reproductive performance in a wide variety of species. In most animals, but not exclusively all, melatonin has an antigonadotrophic effect. The seasonal changes in the number of hours per day that melatonin is secreted mediate the temporal coupling of reproductive activity to seasonal changes in day-length. These observations stimulated a search for a role for the pineal gland and melatonin in human reproduction. Clinical experience related to this issue has yielded inconclusive and sometimes conflicting results. This article reviews the current available evidence concerning the effects of melatonin on human reproductive processes (e.g., puberty, ovulation, pregnancy, and fertility). Possible reasons for the vagueness and elusiveness of the clinical effects are discussed.

Melatonin, Immune Function and Cancer

Melatonin is a natural substance ubiquitous in distribution and present in almost all species ranging from unicellular organisms to humans. In mammals, melatonin is synthesized not only in the pineal gland but also in many other parts of the body, including the eyes, bone marrow, gastrointestinal tract, skin and lymphocytes. Melatonin influences almost every cell and can be traced in membrane, cytoplasmic, mitochondrial and nuclear compartments of the cell. The decline in the production of melatonin with age has been suggested as one of the major contributors to immunosenescence and development of neoplastic diseases. Melatonin is a natural antioxidant with immunoenhancing properties. T-helper cells play an important role for protection against malignancy and melatonin has been shown to enhance T-helper cell response by releasing interleukin-2, interleukin-10 and interferon-γ. Melatonin is effective in suppressing neoplastic growth in a variety of tumors like melanoma, breast and prostate cancer, and ovarian and colorectal cancer. As an adjuvant therapy, melatonin can be beneficial in treating patients suffering from breast cancer, hepatocellular carcinoma or melanoma. In this paper, a brief review of recent patents on melatonin and cancer has also been presented.

Histological definition of the vomeronasal organ in humans and chimpanzees, with a comparison to other primates

The vomeronasal organ (VNO) is a chemosensory structure that has morphological indications of functionality in strepsirhine and New World primates examined to date. In these species, it is thought to mediate certain socio‐sexual behaviors. The functionality and even existence of the VNO in Old World primates has been debated. Most modern texts state that the VNO is absent in Old World monkeys, apes, and humans. A recent study on the VNO in the chimpanzee (Smith et al., 2001b ) challenged this notion, demonstrating the need for further comparative studies of primates. In particular, there is a need to establish how the human/chimpanzee VNO differs from that of other primates and even nonhomologous mucosal ducts. Histochemical and microscopic morphological characteristics of the VNO and nasopalatine duct (NPD) were examined in 51 peri‐ and postnatal primates, including humans, chimpanzees, five species of New World monkeys, and seven strepsirhine species. The nasal septum was removed from each primate and histologically processed for coronal sectioning. Selected anteroposterior intervals of the VNO were variously stained with alcian blue (AB)‐periodic acid‐Schiff (PAS), PAS only, Gomori trichrome, or hematoxylin‐eosin procedures. All strepsirhine species had well developed VNOs, with a prominent neuroepithelium and vomeronasal cartilages that nearly surrounded the VNO. New World monkeys had variable amounts of neuroepithelia, whereas Pan troglodytes and Homo sapiens had no recognizable neuroepithelium or vomeronasal nerves (VNNs). Certain unidentified cell types of the human/chimpanzee VNO require further examination (immunohistochemical and electron microscopic). The VNOs of P. troglodytes, H. sapiens, and New World monkeys exhibited different histochemistry of mucins compared to strepsirhine species. The nasopalatine region showed great variation among species. It is a blind‐ended pit in P. troglodytes, a glandular recess in H. sapiens, a mucous‐producing duct in Otolemur crassicaudatus, and a stratified squamous passageway in all other species. This study also revealed remarkable morphological/histochemical variability in the VNO and nasopalatine regions among the primate species examined. The VNOs of humans and chimpanzees had some structural similarities to nonhomologous ciliated gland ducts seen in other primates. However, certain distinctions from the VNOs of other primates or nonhomologous epithelial structures characterize the human/chimpanzee VNO: 1) bilateral epithelial tubes; 2) a superiorly displaced position in the same plane as the paraseptal cartilages; 3) a homogeneous, pseudostratified columnar morphology with ciliated regions; and 4) mucous‐producing structures in the epithelium itself. Anat Rec 267:166–176, 2002.

The human vomeronasal organ. III. Postnatal development from infancy to the ninth decade

The large literature on the human vomeronasal organ (VNO) offers little consensus as to its persistence in the adult. We have already documented the existence of the VNO from embryonic day 33 through the neonatal stages. This has now been extended to human adults: 27 cadaver nasal septa, aged 2–86 y, were either dissected or decalcified, serially sectioned, stained and examined. The consistent presence of the VNO is reported as a homologue, in the form of a duct‐like structure on the nasal septum at all ages. Also reported are size variability, pronounced bilateral asymmetry, a nonchemosensory pseudostratified ciliated epithelium with considerable structural variation and generally without medial–lateral differentiation, nasal septal glands opening into the VNO lumen, a lack of correlation between postnatal age and VNO size, visualisation of the human VNO with certainty by histological means alone, and a minute opening as its only visible surface feature. The human VNO is a discrete structure that should not be confused with the nasopalatine fossa, the septal mucosal pits or VNO openings.

The human vomeronasal organ. Part II: prenatal development

During the 20th century, the human vomeronasal organ (VNO) has been controversial regarding its structure, function, and even identity. Despite reports that provide evidence for its presence throughout prenatal and postnatal ontogeny, some studies and numerous textbooks declare its absence in late fetal and postnatal humans. To that end, the present study was designed to establish firmly whether the human VNO is homologous with that of other mammals and whether it degenerates (partially or completely) or persists throughout prenatal development. Fifty human embryos and fetuses (33 d to 32 wk fertilisation age) and 2 neonates were examined by light microscopy. Four embryonic primates (mouse lemurs) were examined for a comparison of VNO embryogenesis. The presence or absence and structural characteristics of the VNO and supporting tissues are described. The first appearance of the VNO was in the form of bilateral epithelial thickenings of the nasal septum, the vomeronasal primordium. The primordia invaginated between 37 and 43 d of age and formed the tubular VNO. The tubular VNO was located dorsally at a variable distance from, but was always spatially separated from the paraseptal cartilages. The mouse lemurs examined in this study and other reports from the literature indicate that the human VNO resembles that of primates having functional VNOs until just after a tubular VNO is formed. Examination of the VNO and adjacent tissues suggested that the VNO may lose receptor cells and corresponding vomeronasal nerves and become a ciliated, pseudostratified epithelium between ∼ 12 and 14 wk of age. Our findings indicate the prenatal human VNO goes through 3 successive stages: early morphogenesis, transformation (of the epithelium), and growth. These observations indicated that (1) all embryonic humans develop a vomeronasal organ which is homologous with the VNOs of other mammals, but which has become displaced and highly variable in relative location during embryogenesis; (2) the human vomeronasal organ does not degenerate prenatally, but very likely loses the functional components of the vomeronasal complex of other mammals; and (3) the remnant of the human VNO persists until birth and beyond.