[Precocious puberty and neuropilin-1 signaling in GnRH neurons]. / Signalisation impliquant la neuropiline dans les neurones sécrétant la GnRH - Son rôle dans le déclenchement de la puberté.

The survival of the species depends on two closely interlinked processes: the correct functioning of the reproductive system, and the balance between the energy needs of an individual and the supply of energy sources through feeding. These two processes are regulated in the hypothalamus, which produces neurohormones that control various physiological functions. Among these neurohormones, GnRH controls not only the maturation and function of the reproductive organs, including the ovaries and the testes, during puberty and in adulthood, but also sexual attraction. Recent evidence suggest that neuropilin-1-mediated signaling in GnRH-synthesizing neurons could be a linchpin that holds together various neuroanatomical, physiological and behavioral adaptations involved in triggering puberty and achieving reproductive function.

TITLE: Signalisation impliquant la neuropiline dans les neurones sécrétant la GnRH - Son rôle dans le déclenchement de la puberté. ABSTRACT: La survie d'une espèce dépend de deux processus intimement liés : la reproduction, d'une part, et l'équilibre entre les besoins énergétiques et l'approvisionnement en sources d'énergie par l'alimentation, d'autre part. Ces deux processus sont contrôlés dans le cerveau par l'hypothalamus, qui produit des neurohormones agissant sur l'hypophyse pour piloter diverses fonctions physiologiques. L'une de ces neurohormones, la GnRH, contrôle non seulement la maturation et le fonctionnement des organes reproducteurs, incluant les ovaires et les testicules, lors de la puberté et à l'âge adulte, mais aussi l'attirance sexuelle. De récentes découvertes suggèrent que la signalisation impliquant la neuropiline-1 dans les neurones sécrétant la GnRH jouerait un rôle charnière dans la coordination du neurodéveloppement et des adaptations physiologiques et comportementales nécessaires au déclenchement de la puberté et à l'acquisition de la fonction de reproduction. Dans cet article de synthèse, nous replaçons ces découvertes dans le contexte de récents travaux montrant que les voies de signalisation des sémaphorines de classe 3 sont impliquées dans la physiopathologie non seulement de l'infertilité, mais aussi de l'obésité. Nous discutons également l'implication potentielle des neurones produisant la GnRH dans la perception des odeurs sociales et dans la précocité de la maturation sexuelle. L'hypothèse selon laquelle l'activité de ces neurones au cours du développement postnatal constituerait le chaînon manquant entre la prise de poids, le déclenchement de la puberté et le comportement sexuel, ouvre la voie à une meilleure compréhension de l'implication de l'homéostasie énergétique dans la maturation sexuelle, et pourrait aussi avoir des implications thérapeutiques pour la puberté précoce.

Effects of water pilates on urinary loss, genital self-image and sexual function of elderly women

Descriptive, quasi experimental study with pre and post-test, which aimed to investigate the effects of Water Pilates (PA) on urinary incontinence, genital self-image and sexual function of elderly women. The sample consisted of seventeen elderly women aged 60 years or over, from a city in the interior of Rio Grande do Sul. The International Consultation on Incontinence Questionnaire -Short Form (ICIQ-SF) was used as instruments to assess the impact of UI in quality of life and qualify urinary loss, the Female Sexual Function Index (FSFI) to assess sexual function and Female Genital Self-Image Scale (FGSIS) to assess women's perception of their own genitalia. The PA protocol was performed twice a week for 50 minutes performed for eight weeks, totaling 16 sessions. The protocol was divided into warm-up, strengthening exercises and stretching. It was observed that the sample was composed ofyoung elderly women (69.5 ± 5.9 years), overweight and with low FSFI and FGSIS scores. There was no significant change in the mean values before and after the intervention of the ICIQ-SF, FGSIS and FSFI scores. It was concluded that the PA method had no effect on urinary loss, sexual function and genital self-image.

Role of nuclear and membrane estrogen signaling pathways in the male and female reproductive tract.

Estrogen signaling through the main estrogen receptor, estrogen receptor 1 (ESR1; also known as ERα), is essential for normal female and male reproductive function. Historically, studies of estrogen action have focused on the classical genomic pathway. Although this is clearly the major pathway for steroid hormone actions, these hormones also signal through rapid non-classical effects involving cell membrane actions. Reports of rapid effects of estrogens extend for more than half a century, but recent results have expanded understanding of the identity, structure, function and overall importance of membrane receptors in estrogen responses. Key findings in this field were the immunohistochemical detection of ESR1 in cell membranes and demonstration that a portion of newly synthesized ESR1 is routed to the membrane by palmitoylation. These receptors in the membrane can then signal through protein kinases and other mechanisms following ligand binding to alter cell function. Another crucial advance in the field was development of transgenic mice expressing normal amounts of functional nuclear ESR1 (nESR1) but lacking membrane ESR1 (mESR1). Both male and female transgenic mice lacking mESR1 were infertile as adults, and both sexes had extensive reproductive abnormalities. Transgenic mice lacking mESR1 were highly protected from deleterious effects of neonatal estrogen administration, and estrogen effects on the histone methyltransferase Enhancer of Zeste homolog 2 that are mediated through mESR1 could have significant effects on epigenetic imprinting. In summary, signaling through mESR1 is essential for normal male and female reproductive function and fertility, and is a critical enabler of normal estrogen responses in vivo. Although the precise role of mESR1 in estrogen responses remains to be established, future research in this area should clarify its mechanism of action and lead to a better understanding of how mESR1 signaling works with classical genomic signaling through nESR1 to promote full estrogenic responses.

Arsenic and smokeless tobacco exposure induces DNA damage and oxidative stress in reproductive organs of female Swiss albino mice.

Arsenic contamination in the groundwater of Southern Assam, India is well-documented. A specific type of smokeless tobacco (sadagura, SG) is highly prevalent among the local population. Thus, the present study is aimed to evaluate the toxicological implications of arsenic and smokeless tobacco co-exposure on the reproductive health of female mice. The estrous cycle of experimental animals was monitored for 30 days. Histopathological studies and comet assay of ovarian and uterine tissues were performed after 30 days of exposure to SG and arsenic (sodium arsenite, SA). Oxidative stress was estimated biochemically by taking tissue glutathione, lipid peroxidation (LPO), and superoxide dismutase activity as endpoints. Our findings indicated a prolonged diestrus phase in the SG + L + SA group (p < 0.001). Histopathological study revealed abnormal tissue architecture in treated groups. Comet assay study showed that SG + SA exposure significantly induced DNA damage in test animals. The elevated LPO level in the SG + SA group indicated oxidative stress generation in the reproductive tissues. The present study suggests that female reproductive organs are vulnerable to SA and SG and oxidative stress generation may be the possible mechanism behind DNA damage, impaired follicular growth, atresia, and altered estrous cycle in the mice test system.

Effects of agricultural pesticides on the reproductive system of aquatic wildlife species, with crocodilians as sentinel species.

Agricultural pesticides represent a significant class of endocrine-disrupting chemicals (EDCs) to which non-target organisms around the world are constantly exposed. Laboratory studies have found strong evidence showing the endocrine-disruptive potential of these pesticides at environmentally relevant exposure levels. Since the field of endocrine disruption continues to grow in richness and complexity, this review aims to provide an update on the effects of two agricultural pesticides that act as EDCs: atrazine and endosulfan. We will focus mainly on the effects on crocodilians due to their worldwide occurrence in tropical and sub-tropical wetland ecosystems and their ecological and physiological features, which render them vulnerable to exposure to pesticides with endocrine-disrupting action at all life stages. The results here reviewed provide important insights into the effects of hormonally active agricultural pesticides at cellular, tissue, and organ levels in the reproductive system of crocodiles. A better understanding of the effects of exposure to environmentally relevant doses of EDCs on the reproductive system of crocodilians will contribute to protect and improve the health of both wildlife species and humans.

Evolutionary expansion of apical extracellular matrix is required for the elongation of cells in a novel structure.

One of the fundamental gaps in our knowledge of how novel anatomical structures evolve is understanding the origins of the morphogenetic processes that form these features. Here, we traced the cellular development of a recently evolved morphological novelty, the posterior lobe of D. melanogaster. We found that this genital outgrowth forms through extreme increases in epithelial cell height. By examining the apical extracellular matrix (aECM), we also uncovered a vast matrix associated with the developing genitalia of lobed and non-lobed species. Expression of the aECM protein Dumpy is spatially expanded in lobe-forming species, connecting the posterior lobe to the ancestrally derived aECM network. Further analysis demonstrated that Dumpy attachments are necessary for cell height increases during posterior lobe development. We propose that the aECM presents a rich reservoir for generating morphological novelty and highlights a yet unseen role for aECM in regulating extreme cell height.

Endocrinological Toxicity Secondary to Treatment of Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NENs).

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are increasingly recognized, characterized by prolonged survival even with metastatic disease. Their medical treatment is complex involving various specialties, necessitating awareness of treatment-related adverse effects (AEs). As GEP-NENs express somatostatin receptors (SSTRs), long-acting somatostatin analogs (SSAs) that are used for secretory syndrome and tumor control may lead to altered glucose metabolism. Everolimus and sunitinib are molecular targeted agents that affect glucose and lipid metabolism and may induce hypothyroidism or hypocalcemia, respectively. Chemotherapeutic drugs can affect the reproductive system and water homeostasis, whereas immunotherapeutic agents can cause hypophysitis and thyroiditis or other immune-mediated disorders. Treatment with radiopeptides may temporarily lead to radiation-induced hormone disturbances. As drugs targeting GEP-NENs are increasingly introduced, recognition and management of endocrine-related AEs may improve compliance and the quality of life of these patients.

Impact of estrogens in males and androgens in females.

Androgens and estrogens are known to be critical regulators of mammalian physiology and development. While these two classes of steroids share similar structures (in general, estrogens are derived from androgens via the enzyme aromatase), they subserve markedly different functions via their specific receptors. In the past, estrogens such as estradiol were thought to be most important in the regulation of female biology, while androgens such as testosterone and dihydrotestosterone were believed to primarily modulate development and physiology in males. However, the emergence of patients with deficiencies in androgen or estrogen hormone synthesis or actions, as well as the development of animal models that specifically target androgen- or estrogen-mediated signaling pathways, have revealed that estrogens and androgens regulate critical biological and pathological processes in both males and females. In fact, the concept of "male" and "female" hormones is an oversimplification of a complex developmental and biological network of steroid actions that directly impacts many organs. In this Review, we will discuss important roles of estrogens in males and androgens in females.

Some assembly required: evolutionary and systems perspectives on the mammalian reproductive system.

In this review, we discuss the way that insights from evolutionary theory and systems biology shed light on form and function in mammalian reproductive systems. In the first part of the review, we contrast the rapid evolution seen in some reproductive genes with the generally conservative nature of development. We discuss directional selection and coevolution as potential drivers of rapid evolution in sperm and egg proteins. Such rapid change is very different from the highly conservative nature of later embryo development. However, it is not unique, as some regions of the sex chromosomes also show elevated rates of evolutionary change. To explain these contradictory trends, we argue that it is not reproductive functions per se that induce rapid evolution. Rather, it is the fact that biotic interactions, such as speciation events and sexual conflict, have no evolutionary endpoint and hence can drive continuous evolutionary changes. Returning to the question of sex chromosome evolution, we discuss the way that recent advances in evolutionary genomics and systems biology and, in particular, the development of a theory of gene balance provide a better understanding of the evolutionary patterns seen on these chromosomes. We end the review with a discussion of a surprising and incompletely understood phenomenon observed in early embryos: namely the Warburg effect, whereby glucose is fermented to lactate and alanine rather than respired to carbon dioxide. We argue that evolutionary insights, from both yeasts and tumor cells, help to explain the Warburg effect, and that new metabolic modeling approaches are useful in assessing the potential sources of the effect.

The SCF/c-KIT system in the male: Survival strategies in fertility and cancer.

Maintaining the delicate balance between cell survival and death is of the utmost importance for the proper development of germ cells and subsequent fertility. On the other hand, the fine regulation of tissue homeostasis by mechanisms that control cell fate is a factor that can prevent carcinogenesis. c-KIT is a type III receptor tyrosine kinase activated by its ligand, stem cell factor (SCF). c-KIT signaling plays a crucial role in cell fate decisions, specifically controlling cell proliferation, differentiation, survival, and apoptosis. Indeed, deregulating the SCF/c-KIT system by attenuation or overactivation of its signaling strength is linked to male infertility and cancer, and rebalancing its activity via c-KIT inhibitors has proven beneficial in treating human tumors that contain gain-of-function mutations or overexpress c-KIT. This review addresses the roles of SCF and c-KIT in the male reproductive tract, and discusses the potential application of c-KIT target therapies in disorders of the reproductive system.

It is as it does: genital form and function in sex reassignment surgery.

Surgeons who perform sex reassignment surgeries (SRS) define their goals and evaluate their outcomes in terms of two kinds of results: aesthetic and functional. Since the neogenitals fashioned through sex reassignment surgeries do not enable reproductive function, surgeons must determine what the function of the genitals is or ought to be. A review of surgical literature demonstrates that questions of what constitute genital form and function, while putatively answered in the operating room, are not answerable in the discourses of clinical evaluation used to define them. When the genitals--the word itself derived from the Latin genitas meaning to beget--are not reproductive, the question of their function shifts away from the biological and into other registers: pleasure, intimacy, sociality. As condensed sites of meaning and meaning-making around which selves, affects, resources, anxieties and futures are organized, the genitals signify in excess of the categories of "aesthetic" and "function" that surgeons use to assess them. Not reducible to either aesthetics or function, but constitutive of them both, this excess appears in surgical texts in the form of imagined futures of social and sexual engagement and demonstrates a powerful means by which properly sexed bodies are created.

Sex differences in Siberian hamster ultradian locomotor rhythms.

Sex differences in ultradian activity rhythms (URs) and circadian rhythms (CRs) were assessed in Siberian hamsters kept in long day (LD) or short day (SD) photoperiods for 40 weeks. For both sexes URs of locomotor activity were more prevalent, greater in amplitude and more robust in SDs. The UR period was longer in females than males in both day lengths. The reproductive system underwent regression and body mass declined during the initial 10 weeks of SD treatment, and in both sexes these traits spontaneously reverted to the LD phenotype at or before 40 weeks in SD, reflecting the development of neuroendocrine refractoriness to SD patterns of melatonin secretion. Hamsters of both sexes, however, continued to display SD-like URs at the 40 weeks time point. CRs were less prevalent and the waveform less robust and lower in amplitude in SDs than LDs; the SD circadian waveform also did not revert to the long-day phenotype after 40 weeks of SD treatment. Short day lengths enhanced ultradian and diminished circadian rhythms in both sexes. Day length controls several UR characteristics via gonadal steroid and melatonin-independent mechanisms. Sex differences in ultradian timing may contribute to sex diphenisms in rhythms of sleep, food intake and exercise.

Tissue engineering of reproductive tissues and organs.

Regenerative medicine and tissue engineering technology may soon offer new hope for patients with serious injuries and end-stage reproductive organ failure. Scientists are now applying the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that can restore and maintain normal function in diseased and injured reproductive tissues. In addition, the stem cell field is advancing, and new discoveries in this field will lead to new therapeutic strategies. For example, newly discovered types of stem cells have been retrieved from uterine tissues such as amniotic fluid and placental stem cells. The process of therapeutic cloning and the creation of induced pluripotent cells provide still other potential sources of stem cells for cell-based tissue engineering applications. Although stem cells are still in the research phase, some therapies arising from tissue engineering endeavors that make use of autologous adult cells have already entered the clinic. This article discusses these tissue engineering strategies for various organs in the male and female reproductive tract.

Stem cells in the reproductive system.

This review article summarizes current knowledge on regulation, functions, and capacities of stem cells in the female and male reproductive tract. Major locations in which pluripotent cells reside and from where they can be isolated are the ovaries, the endometrium, the decidua, and the testis. They include oocytes, embryonic stem cells, trophoblast stem cells, and spermatogonial stem cells, but also several side populations, which can be obtained after certain isolation and culture procedures. The potential of pluripotent cells in the reproductive tract to differentiate is manifold, but heterogenous, depending upon their respective origin. As stem cells have a potential for future application in transplantation and regenerative medicine, this article also reviews the literature on major histocompatibility complex expression on stem cells of the reproductive tract, because of its immunogenic effects, but also because of its potential expression of HLA-G, a potent immunomodulator mainly associated with trophoblast cells.

Morphology of the male agouti accessory genital glands (Dasyprocta prymnolopha Wagler, 1831) / / Morfologia das glândulas genitais acessórias em cutias (Dasyprocta prymnolopha Wagler, 1831)

The morphology of the accessory genital glands of the male agouti was studied in twenty-three animals that were raised in captivity. Twenty animals had their genital glands dissected in situ for macroscopic description. The samples of each gland were recovered, embedded in paraffin, sliced and stained by Hematoxylin-Eosin technique. It was founded four pairs of glands: the vesicular glands, the coagulating glands, the prostate and the bulbourethral glands. Histological characteristics of the vesicular, coagulating and prostate glands showed similar morphology, within the pseudostratified columnar epithelium. The tubulo-alveolar type of the bulbourethral glands showed a lack of connective tissue among the tubules, a small amount of red stained presented it the cytoplasm, and the presence of vacuoles in the tissue. This study concluded that the agouti showed to have similar morphological aspect described in the others species of rodents.

A morfologia das glândulas genitais acessórias de cutias foram estudados em 23 animais criados em cativeiros. Vinte animais tiveram suas glândulas genitais dissecadas in situ para as descrições macroscópicas. Para o estudo microscópico foram utilizados três animais. Os fragmentos de cada glândula foram embebidos em parafina, seccionados e corados em hematoxilina e eosina. Foram encontrados quatro pares de glândulas: vesiculares, coaguladoras, próstata e bulbouretrais. As características histológicas da glândula vesicular, coaguladora e próstata mostraram morfologia similar, com epitélio colunar pseudoestratificado. O tipo tuboalveolar da glândula bulbouretral mostrou uma deficiência de tecido conjuntivo, citoplasma pouco corado e presença de vacúolos. Este estudo concluiu que a cutia apresenta as mesmas características morfológicas das glândulas genitais acessórias encontradas em roedores.

Toll-like receptors in the gonads and reproductive tract: emerging roles in reproductive physiology and pathology.

Interactions between the immune system and reproductive system have important consequences for fertility and reproductive health in general. There is increasing evidence that many of the interactions between the immune and reproductive systems involve the Toll-like receptors (TLRs). While there is no doubt that TLRs are important in providing protection against infection in the reproductive tract, there is increasing evidence for the involvement of TLRs in more basic pathology and physiology of reproduction. In the female, TLRs have been implicated in critical aspects of ovarian, endometrial and placental function, as well as in ovarian cancer, pelvic inflammatory disease, intrauterine growth restriction, pre-eclampsia and preterm birth. In the male, TLRs appear to play a role in the control of testicular steroidogenesis and spermatogenesis in disease and, potentially, during normal function, as well. Recent studies also have begun to highlight the role of various TLRs in the aetiology of prostatitis and prostatic cancer. Given the nascent state of knowledge concerning this important area, it is clear that more studies are needed, which should provide valuable new insights into the biology of the TLRs and reproductive function in general.

New aspects of cadmium as endocrine disruptor.

Cadmium (Cd) is an industrial and environmental pollutant that exerts adverse effects on a number of organs in humans and animals. Reproductive organs, such as the testis and placenta, are sensitive to the toxic effects of Cd. In animal experiments, high-dose exposure to Cd induced severe testicular interstitial hemorrhage with edema, and increased incidence of fetal death and placental necrosis. Low-dose exposure to Cd affects steroid synthesis in male and female reproductive organs. In 1998, the Ministry of Environment in Japan listed Cd in the strategy plan SPEED98 as one of the chemicals suspected of having possible endocrine disrupting activity. Recently, it has been shown that Cd has potent estrogen- and androgen-like activities in vivo and in vitro, by directly binding to estrogen and androgen receptors. However, the precise mechanisms underlying the effects of Cd as an endocrine disruptor remain to be elucidated. In this review, we will discuss evidence thus far presented concerning the effects of Cd on the endocrine system.

Effects of paradoxical sleep deprivation on genital reflexes in five rat strains.

This study examined the effects of cocaine on genital reflexes in paradoxical sleep-deprived (PSD) male rats of five strains since it has been demonstrated that this drug enhances genital reflexes in Wistar PSD rats. At the end of a 4-day period of PSD or at the equivalent time-point to control animals, cocaine or saline was acutely administered to the animals and penile erection (PE) and ejaculation (EJ) were quantified. Results indicated that PSD induced genital reflexes in all strains, and cocaine potentiated these behaviors in Wistar and Long-Evans rats. Wistar PSD rats injected with cocaine performed significantly more PE than all the other PSD + cocaine strains. The number of Wistar and Long-Evans PSD + cocaine ejaculating was significantly higher than the respective PSD + saline and control, whereas a tendency of increase was seen in relation to other groups. Wistar PSD + cocaine rats showed the highest EJ frequency compared to F344, Sprague-Dawley and Wistar-Kyoto strains, and the Long-Evans displayed more EJ than Sprague-Dawley and Wistar-Kyoto. Analysis of testosterone concentrations revealed that after sleep deprivation, Wistar, Long-Evans, and F344 rats showed significantly lower testosterone concentrations than control rats. In F344, Sprague-Dawley and Wistar-Kyoto controls rats, testosterone was significantly lower than in the control Wistar and Long-Evans. Progesterone concentrations were significantly higher in Wistar and Long-Evans PSD rats than in respective control groups. In the other strains, this hormone was significantly lower compared to the Wistar and Long-Evans PSD. This study demonstrates that genital reflexes are differently influenced by PSD associated to cocaine in five rat strains.

Immunohistochemical evidence for an endocrine/paracrine role for ghrelin in the reproductive tissues of sheep.

BACKGROUND: The gut hormone, ghrelin, is involved in the neuroendocrine and metabolic responses to hunger. In monogastric species, circulating ghrelin levels show clear meal-related and body weight-related changes. The pattern of secretion and its role in ruminant species is less clear. Ghrelin acts via growth hormone secretagogue receptors (GHSR-1a) to alter food intake, fat utilization, and cellular proliferation. There is also evidence that ghrelin is involved in reproductive function. In the present study we used immunohistochemistry to investigate the presence of ghrelin and GHSR-1a in sheep reproductive tissues. In addition, we examined whether ghrelin and GHSR-1a protein expression is developmentally regulated in the adult and fetal ovine testis, and whether there is an association with markers of cellular proliferation, i.e. stem cell factor (SCF) and proliferating cell nuclear antigen (PCNA). METHODS: Antibodies raised against ghrelin and its functional receptor, GHSR-type 1a, were used in standard immunohistochemical protocols on various reproductive tissues collected from adult and fetal sheep. GHSR-1a mRNA presence was also confirmed by in situ hybridisation. SCF and PCNA immunoexpression was investigated in fetal testicular samples. Adult and fetal testicular immunostaining for ghrelin, GHSR-1a, SCF and PCNA was analysed using computer-aided image analysis. Image analysis data were subjected to one-way ANOVA, with differences in immunostaining between time-points determined by Fisher's least significant difference. RESULTS: In adult sheep tissue, ghrelin and GHSR-1a immunostaining was detected in the stomach (abomasum), anterior pituitary gland, testis, ovary, and hypothalamic and hindbrain regions of the brain. In the adult testis, there was a significant effect of season (photoperiod) on the level of immunostaining for ghrelin (p < 0.01) and GHSR-1a (p < 0.05). In the fetal sheep testis, there was a significant effect of gestational age on the level of immunostaining for ghrelin (p < 0.001), GHSR-1a (p < 0.05), SCF (p < 0.05) and PCNA (p < 0.01). CONCLUSION: Evidence is presented for the presence of ghrelin and its receptor in various reproductive tissues of the adult and fetal sheep. In addition, the data indicate that testicular expression of ghrelin and its receptor is physiologically regulated in the adult and developmentally regulated in the fetus. Therefore, the ghrelin ligand/receptor system may have a role (endocrine and/or paracrine) in the development (cellular proliferation) and function of the reproductive axis of the sheep.