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Hormones and Behavior Mar 2024Early life adversity in the form of childhood maltreatment in humans or as modeled by maternal separation (MS) in rodents is often associated with an earlier emergence...
Early life adversity in the form of childhood maltreatment in humans or as modeled by maternal separation (MS) in rodents is often associated with an earlier emergence of puberty in females. Earlier pubertal initiation is an example of accelerated biological aging and predicts later risk for anxiety in women, especially in populations exposed to early life trauma. Here we investigated external pubertal markers as well as hypothalamic gene expression of pubertal regulators kisspeptin and gonadotropin-releasing hormone, to determine a biological substrate for MS-induced accelerated puberty. We further investigated a mechanism by which developmental stress might regulate pubertal timing. As kisspeptin and gonadotropin-releasing hormone secretion are typically inhibited by corticotropin releasing hormone at its receptor CRH-R1, we hypothesized that MS induces a downregulation of Crhr1 gene transcription in a cell-specific manner. Finally, we explored the association between pubertal timing and anxiety-like behavior in an acoustic startle paradigm, to drive future preclinical research linking accelerated puberty and anxiety. We replicated previous findings that MS leads to earlier puberty in females but not males, and found expression of kisspeptin and gonadotropin-releasing hormone mRNA to be prematurely increased in MS females. RNAscope confirmed increased expression of these genes, and further revealed that kisspeptin-expressing neurons in females were less likely to express Crhr1 after MS. Early puberty was associated with higher acoustic startle magnitude in females. Taken together, these findings indicate precocial maturation of central pubertal timing mechanisms after MS, as well as a potential role of CRH-R1 in these effects and an association with a translational measure of anxiety.
Topics: Humans; Rats; Female; Animals; Kisspeptins; Adverse Childhood Experiences; Maternal Deprivation; Hypothalamus; Gonadotropin-Releasing Hormone; Sexual Maturation
PubMed: 38241961
DOI: 10.1016/j.yhbeh.2024.105478 -
Frontiers in Neuroanatomy 2023The catecholaminergic component of the brain-pituitary-gonadal axis, which mediates the influence of external and internal stimuli on the central nervous system and...
Ontogenetic changes in the tyrosine hydroxylase immunoreactive preoptic area in the small-spotted catshark (L., 1758) females: catecholaminergic involvement in sexual maturation.
INTRODUCTION
The catecholaminergic component of the brain-pituitary-gonadal axis, which mediates the influence of external and internal stimuli on the central nervous system and gonad development in vertebrates, is largely unexplored in Chondrichthyes. We considered (L., 1758) females as a model for this vertebrate's class, to assess the involvement of the catecholaminergic system of the brain in its reproduction. Along the reproductive cycle, we characterized and evaluated differences in somata morphometry and the number of putative catecholaminergic neurons in two brain nuclei: the periventricular preoptic nucleus, hypothesized to be a positive control for ovarian development, and the suprachiasmatic nucleus, examined as a negative control.
MATERIALS AND METHODS
16 wild females were sampled and grouped in maturity stages (immature, maturing, mature, and mature egg-laying). The ovary was histologically processed for the qualitative description of maturity stages. Anti-tyrosine hydroxylase immunofluorescence was performed on the diencephalic brain sections. The immunoreactive somata were investigated for morphometry and counted using the optical fractionator method, throughout the confocal microscopy.
RESULTS AND DISCUSSIONS
Qualitative and quantitative research confirmed two separate populations of immunoreactive neurons. The modifications detected in the preoptic nucleus revealed that somata were more numerous, significantly smaller in size, and more excitable during the maturing phase but decreased, becoming slightly bigger and less excitable in the egg-laying stage. This may indicate that the catecholaminergic preoptic nucleus is involved in the control of reproduction, regulating both the onset of puberty and the imminent spawning. In contrast, somata in the suprachiasmatic nucleus grew in size and underwent turnover in morphometry, increasing the total number from the immature-virgin to maturing stage, with similar values in the more advanced maturity stages. These changes were not linked to a reproductive role. These findings provide new valuable information on Chondrichthyes, suggesting the existence of an additional brain system implicated in the integration of internal and environmental cues for reproduction.
PubMed: 38239387
DOI: 10.3389/fnana.2023.1301651 -
Frontiers in Endocrinology 2023Cryptorchidism in males constitutes a notable risk factor for both infertility and testicular cancer. Infertility in adulthood is closely linked to the germ cell status... (Review)
Review
Cryptorchidism in males constitutes a notable risk factor for both infertility and testicular cancer. Infertility in adulthood is closely linked to the germ cell status in childhood. Furthermore, the significance of germ cell status is important as more than 95% of all reported testicular malignancies are germ cell tumors. The review aims to elucidate the pathogenesis of germ cells in cryptorchid testes concerning their association with infertility and testicular malignancies. Impaired germ cell numbers are evident in cryptorchid testes even during antenatal and neonatal stages. In cryptorchidism there is a rapid decline in germ cell number within the first year of life, partially attributed to physiologic gonocyte apoptosis. Additionally, germ cells fail to differentiate normally during mini-puberty leading to reduced germ cell proliferation and delayed clearance of gonocytes from the seminiferous epithelium. Absence of germ cells in testicular biopsies occurs already 10 months of age and germ cell deterioration progressively worsens with approximately 50% of persisting cryptorchid testes lacking germ cells during puberty. The deficient germ cell maturation and proliferation leads to later infertility. Elevated temperature in the cryptorchid testes and also hormonal deficiency contribute to this phenomenon. Germ cell neoplasia (GCNIS) originating during fetal development may manifest in rare cases associated with disorders of sexual development, chromosomal abnormalities in boys, specific syndromes, and teratomas that include cryptorchidism. In adults, the presence of GCNIS predominantly represents a new histology pattern before invasive germ cell cancer is demonstrated and is neither congenital nor related to abnormal gonocyte transformation.
Topics: Humans; Male; Cryptorchidism; Germ Cells; Infertility; Testicular Neoplasms
PubMed: 38234428
DOI: 10.3389/fendo.2023.1305428 -
Scientific Reports Jan 2024The loggerhead sea turtle (Caretta caretta) is sensitive to climate change and is responding by colonising the Western Mediterranean. To understand the rapid nesting...
The loggerhead sea turtle (Caretta caretta) is sensitive to climate change and is responding by colonising the Western Mediterranean. To understand the rapid nesting increase in recent years in Spain, we sampled 45 hatchlings from 8 nests between 2016 and 2019. We sequenced a mtDNA D-loop region, genotyped 2291 SNPs using 2bRAD and collected data on clutch size, hatching success, and incubation duration. We confirmed that the colonisation has a Mediterranean and Atlantic mixed origin and we detected that these nests were laid by different females, except for two nests within the same season. Our results suggest that the recent increase in nesting is due to an increase in the number of colonising individuals rather than females born in the same area returning to breed. We hypothesize that this increase in the number of colonisers results from successful conservation efforts, feminisation of the populations of origin and earlier sexual maturation. However, the percentage of offspring females produced in Spain suggests that future returning individuals will aid to the settlement of the new population. These results allow defining the current status of this colonisation although future efforts are needed to detect remigrants to confirm the establishment of a resident population.
Topics: Animals; Female; Humans; Turtles; DNA, Mitochondrial; Mitochondria; Clutch Size; Sexual Maturation; Nesting Behavior
PubMed: 38233518
DOI: 10.1038/s41598-024-51664-w -
Molecular Medicine (Cambridge, Mass.) Jan 2024Male infertility is a physiological phenomenon in which a man is unable to impregnate a fertile woman during a 12-month period of continuous, unprotected sexual... (Review)
Review
Male infertility is a physiological phenomenon in which a man is unable to impregnate a fertile woman during a 12-month period of continuous, unprotected sexual intercourse. A growing body of clinical and epidemiological evidence indicates that the increasing incidence of male reproductive problems, especially infertility, shows a very similar trend to the incidence of diabetes within the same age range. In addition, a large number of previous in vivo and in vitro experiments have also suggested that the complex pathophysiological changes caused by diabetes may induce male infertility in multiple aspects, including hypothalamic-pituitary-gonadal axis dysfunction, spermatogenesis and maturation disorders, testicular interstitial cell damage erectile dysfunction. Based on the above related mechanisms, a large number of studies have focused on the potential therapeutic association between diabetes progression and infertility in patients with diabetes and infertility, providing important clues for the treatment of this population. In this paper, we summarized the research results of the effects of diabetes on male reproductive function in recent 5 years, elaborated the potential pathophysiological mechanisms of male infertility induced by diabetes, and reviewed and prospected the therapeutic measures.
Topics: Female; Humans; Male; Infertility, Male; Diabetes Mellitus; Leydig Cells
PubMed: 38225568
DOI: 10.1186/s10020-023-00771-x -
Current Biology : CB Feb 2024In mammals, maternal photoperiodic programming (MPP) provides a means whereby juvenile development can be matched to forthcoming seasonal environmental conditions. This...
In mammals, maternal photoperiodic programming (MPP) provides a means whereby juvenile development can be matched to forthcoming seasonal environmental conditions. This phenomenon is driven by in utero effects of maternal melatonin on the production of thyrotropin (TSH) in the fetal pars tuberalis (PT) and consequent TSH receptor-mediated effects on tanycytes lining the 3 ventricle of the mediobasal hypothalamus (MBH). Here we use LASER capture microdissection and transcriptomic profiling to show that TSH-dependent MPP controls the attributes of the ependymal region of the MBH in juvenile animals. In Siberian hamster pups gestated and raised on a long photoperiod (LP) and thereby committed to a fast trajectory for growth and reproductive maturation, the ependymal region is enriched for tanycytes bearing sensory cilia and receptors implicated in metabolic sensing. Contrastingly, in pups gestated and raised on short photoperiod (SP) and therefore following an over-wintering developmental trajectory with delayed sexual maturation, the ependymal region has fewer sensory tanycytes. Post-weaning transfer of SP-gestated pups to an intermediate photoperiod (IP), which accelerates reproductive maturation, results in a pronounced shift toward a ciliated tanycytic profile and formation of tanycytic processes. We suggest that tanycytic plasticity constitutes a mechanism to tailor metabolic development for extended survival in variable overwintering environments.
Topics: Cricetinae; Animals; Ependymoglial Cells; Seasons; Hypothalamus; Circadian Rhythm; Phodopus; Photoperiod; Thyrotropin; Melatonin
PubMed: 38218183
DOI: 10.1016/j.cub.2023.12.042 -
Journal of Traditional Chinese Medicine... Feb 2024To elucidate the mechanism of the nourishing and purging fire Chinese herbal mixture (NYPF) in delaying light-induced premature puberty in rats.
OBJECTIVE
To elucidate the mechanism of the nourishing and purging fire Chinese herbal mixture (NYPF) in delaying light-induced premature puberty in rats.
METHODS
Twenty-one days old female Sprague-Dawley rats were randomly assigned to normal group (N), long light exposure group (L), NYPF and normal saline group (NS). Rats in the L, NYPF and NS groups were exposed to 16 h: 350 lux light/8 h: dark, while rats in the N group were exposed to 12 h: 50 lux light/12 h: dark. NYPF and normal saline was administered to the rats in the NYPF group or NS group, respectively, from day 21. Five rats in every group were sacrificed at 9 p.m. on day 28 (P28), on the day when rat's vulva opened in the L group (L-VO), on the day when the first estrous interphase occurred in rats of L group (L-E1), and on the day when the second estrous interphase occurred in rats of L group (L-E2), respectively.
RESULITS
On day 34, all rats in the L group, 80% of rats in the NS group, 40% of rats in the N group, and 20% of rats in the NYPF group showed complete opening of the vulva. At P28, mRNA level of hypothalamic kisspeptin (Kiss-1) in the L group was significantly higher than that in the N group ( 0.05). The rats in the L and NS groups had significantly lower hypothalamic arginine-phenylalanine-amide (RFamide)-related peptide 3 (RFRP-3) mRNA levels than those in the N group ( 0.05), whereas RFRP-3 mRNA level was significantly higher in the NYPF group than that in the L group ( 0.05). At L-VO, the ovarian index of the L and NS groups was significantly higher than that of the N group ( 0.05) and estradiol (E2) level of the NYPF group was significantly lower than that of the N and NS groups ( 0.05); hypothalamic Kiss-1 mRNA level in the L and NS groups was significantly higher than that in the N and NYPF groups ( 0.05), whereas hypothalamic RFRP-3 mRNA level in the L, NYPF, and NS groups was significantly lower than that in the N group ( 0.05). At L-E1, E2 level of the L and NS groups was significantly higher than that of the N group ( 0.01), whereas it was significantly lower in the NYPF group than that of the N, L, and NS groups ( 0.01), and serum luteinizing hormone level of the L and NS groups was significantly higher than that of the N group ( 0.05); levels of serum melatonin and ovarian melatonin receptor 1 (MT-1) mRNA in the L, NYPF, and NS groups were significantly lower than those in the N group ( 0.05). At L-E2, the uterine organ index of the NYPF group was significantly lower than that of the L group ( 0.05); and ovarian MT-1 mRNA level of the L and NS groups was significantly lower than that in the N group ( 0.05).
CONCLUSIONS
NYPF can delay puberty onset in rats exposed to strong light for a prolonged duration, and regulation of the gene expression of Kiss-1 and RFRP-3 in the hypothalamus has been suggested as one of the mechanisms.
Topics: Rats; Animals; Female; Rats, Sprague-Dawley; Kisspeptins; Saline Solution; Sexual Maturation; Hypothalamus; RNA, Messenger
PubMed: 38213244
DOI: 10.19852/j.cnki.jtcm.20230814.001 -
Scientific Reports Jan 2024The genitourinary symptom of menopause (GSM) affects up to 65% of women, resulting in symptoms such as vulvovaginal dryness, discomfort, and dysuria, which significantly...
The genitourinary symptom of menopause (GSM) affects up to 65% of women, resulting in symptoms such as vulvovaginal dryness, discomfort, and dysuria, which significantly impacts quality of life. The current assessment methods rely on subjective questionnaires that can be influenced by individual differences, as well as invasive measurements that are time-consuming and not easily accessible. In this study, we explore the potential of a non-invasive and objective assessment tool called diffuse reflectance spectroscopy and imaging (DRSI) to evaluate tissue chromophores, including water, lipid, oxyhemoglobin, and deoxyhemoglobin. These measurements provide information about moisture content, lipid levels, oxygen saturation, and blood fraction, which can serve as surrogate markers for genital estrogen levels. Our findings reveal distinct differences in these chromophores among pre, peri, and postmenopausal subjects. By using lipid and blood fraction tissue chromophores in a K-Nearest Neighbour classifier model, we achieved a prediction accuracy of 65% compared to vaginal maturation index (VMI) that is clinically used to assess estrogen-related hormonal changes. When age was included as the third feature, the accuracy increased to 78%. We believe that by refining the study protocol and configuring the fiber probe to examine tissue chromophores both in the superficial vulva skin for epidermal water content and the deeper layers, DRSI has the potential to provide objective diagnosis and aid in monitoring the treatment outcome of GSM.
Topics: Female; Humans; Pilot Projects; Quality of Life; Menopause; Vagina; Spectrum Analysis; Estrogens; Water; Lipids; Atrophy
PubMed: 38212347
DOI: 10.1038/s41598-023-49655-4 -
Complementary Medicine Research 2024Urogenital atrophy and its sequelae, particularly genital dryness, urological problems, and pain on genital touching, are common medical problems for menopausal women...
INTRODUCTION
Urogenital atrophy and its sequelae, particularly genital dryness, urological problems, and pain on genital touching, are common medical problems for menopausal women and women undergoing antihormonal cancer treatment. To meet the requirements for a nonhormonal local treatment, a compounded herbal preparation was developed as a vaginal ovule (Dioscorea comp. ovulum), and the efficacy and applicability of this herbal treatment were investigated.
METHODS
This was a retrospective chart review of patients' records. The study was approved by the Ethics Committee of the Canton of Zurich (project number BASEC 2016-01982). Between 2007 and 2011, patients with urogenital atrophy and related symptoms, who wanted to initiate herbal treatment, were asked for consent to be interviewed (4-point rating scale) and examined gynecologically with photo documentation of their vaginal discharge. A total of 26 patients met the enrollment criteria and consented to the procedure. The first 8 weeks consisted of a daily application of low-dose Dioscorea comp. ovulum followed by high-dose Dioscorea comp. ovule twice weekly for at least 3 months.
RESULT
A total of 23 patients completed the trial. Of the 19 patients in the subgroup with an atrophic vaginal maturation index (VMI), 16 achieved a eutrophic VMI. Four patients began therapy with hypotrophy. There was a 96% decrease in complaints (22/23). The genital dryness score decreased from 1.80 to 0.25 points, urological problems from 2.38 to 0.85 points, and pain on genital touching from 1.70 to 0.60 points. Application, tolerability, and medical safety of the formula were good.
CONCLUSION
The phytotherapeutic compounded preparation Dioscorea comp. ovule (Dioscorea villosa, Glycine max, Salvia officinalis) is suitable for the treatment of urogenital atrophy and its sequelae.
UNLABELLED
Hintergrund Urogenitale Atrophie und ihre Folgeerscheinungen, insbesondere genitale Trockenheit, urologische Probleme und schmerzhafte genitale Berührungen, sind ein häufiges medizinisches Problem bei menopausalen Frauen und Frauen unter antihormoneller Krebstherapie. Um den Bedarf an einer nicht-hormonellen lokalen Behandlung zu decken, wurde ein pflanzliches Präparat in Form eines Vaginal-Ovulum (Dioscorea comp. Ovulum) entwickelt. Wirksamkeit und Anwendbarkeit dieser pflanzlichen Behandlung werden untersucht.Patientinnen und Methoden Es handelt sich um eine retrospektive Analyse. Das Studienprotokoll wurde von der Ethikkommission des Kantons Zürich genehmigt (Projekt Nummer BASEC 2016-01982). Zwischen 2007 und 2011 wurden geeignete Patientinnen mit urogenitaler Atrophie und assoziierten Beschwerden, die mit einer pflanzlichen Behandlung beginnen wollten, um ihr Einverständnis zu einer Befragung (4-Punkte-Score) und gynäkologischen Untersuchungen mit Fotodokumentation des Vaginalausflusses (Nativpräparat) gebeten. 26 Patientinnen erfüllten die Kriterien und erklärten sich mit dem Verfahren einverstanden.Behandlung Nach einer täglichen Anwendung eines niederdosiertenDioscorea comp. Ovulum folgte eine zweimal wöchentliche Anwendung des höher dosiertenDioscorea comp. Ovulum für mindestens 3 Monate.Ergebnisse Insgesamt 23 Patientinnen schlossen die Studie ab. 16 von 19 Patientinnen in der Untergruppe mit einem atrophen Vaginalen Maturations-Index (VMI) erreichten ein eutrophes Vaginalepithel. Vier Patientinnen begannen mit einer Hypotrophie. Ein Rückgang der Beschwerden wurde bei 96% (22 von 23) erreicht: Trockenheit im Genitalbereich ging von 1,80 auf 0,25 Score-Punkte zurück, urologische Probleme von 2,38 auf 0,85 Score-Punkte und schmerzhafte Berührungen im Genitalbereich von 1,70 auf 0,60 Score-Punkte. Anwendung, Verträglichkeit und medizinische Sicherheit der Magistralrezeptur sind gut.Schlussfolgerung Das phytotherapeutische KombinationspräparatDioscorea comp. Ovulum (Dioscorea villosa L., Glycine Max Merr., Salvia officinalis L.) eignet sich zur Behandlung der urogenitalen Atrophie und ihrer Folgeerscheinungen.PubMed: 38211573
DOI: 10.1159/000536193 -
PLoS Genetics Jan 2024Meiosis is a highly conserved feature of sexual reproduction that ensures germ cells have the correct number of chromosomes prior to fertilization. A subset of...
Meiosis is a highly conserved feature of sexual reproduction that ensures germ cells have the correct number of chromosomes prior to fertilization. A subset of microtubules, known as the spindle, are essential for accurate chromosome segregation during meiosis. Building evidence in mammalian systems has recently highlighted the unexpected requirement of the actin cytoskeleton in chromosome segregation; a network of spindle actin filaments appear to regulate many aspects of this process. Here we show that Drosophila oocytes also have a spindle population of actin that appears to regulate the formation of the microtubule spindle and chromosomal movements throughout meiosis. We demonstrate that genetic and pharmacological disruption of the actin cytoskeleton has a significant impact on spindle morphology, dynamics, and chromosome alignment and segregation during maturation and the metaphase-anaphase transition. We further reveal a role for calcium in maintaining the microtubule spindle and spindle actin. Together, our data highlights potential conservation of morphology and mechanism of the spindle actin during meiosis.
Topics: Animals; Actins; Drosophila; Spindle Apparatus; Meiosis; Microtubules; Oocytes; Actin Cytoskeleton; Chromosome Segregation; Mammals
PubMed: 38206959
DOI: 10.1371/journal.pgen.1011111