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International Journal of Molecular... Nov 2023Kisspeptin, a neuropeptide encoded by the gene, combines with its receptor Kiss1R to regulate the onset of puberty and male fertility by the...
Kisspeptin, a neuropeptide encoded by the gene, combines with its receptor Kiss1R to regulate the onset of puberty and male fertility by the hypothalamic-pituitary-gonadal axis. However, little is known regarding the expression signatures and molecular functions of in the testis. H&E staining revealed that well-arranged spermatogonia, spermatocytes, round and elongated spermatids, and spermatozoa, were observed in 4-, 6-, and 8-month-old testes compared to 1- and 3-month-old testes of Hezuo pigs; however, these were not observed in Landrance until 6 months. The diameter, perimeter, and cross-sectional area of seminiferous tubules and the perimeter and area of the tubular lumen increased gradually with age in both pigs. Still, Hezuo pigs grew faster than Landrance. The cloning results suggested that the Hezuo pigs' CDS region is 417 bp in length, encodes 138 amino acids, and is highly conserved in the kisspeptin-10 region. qRT-PCR and Western blot indicated that the expression trends of mRNA and protein were essentially identical, with higher expression levels at post-pubertal stages. Immunohistochemistry demonstrated that the Kiss1 protein was mainly located in Leydig cells and post-pubertal spermatogenic cells, ranging from round spermatids to spermatozoa. These studies suggest that Kiss1 is an essential regulator in the onset of puberty and spermatogenesis of boars.
Topics: Male; Animals; Swine; Testis; Kisspeptins; Sexual Maturation; Spermatids; Reproduction
PubMed: 38069021
DOI: 10.3390/ijms242316700 -
Cells Nov 2023Abnormal sexual maturity exhibits significant detrimental effects on adult health outcomes, and previous studies have indicated that targeting histone acetylation might...
Abnormal sexual maturity exhibits significant detrimental effects on adult health outcomes, and previous studies have indicated that targeting histone acetylation might serve as a potential therapeutic approach to regulate sexual maturity. However, the mechanisms that account for it remain to be further elucidated. Using the mouse model, we showed that Trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, downregulated the protein level of Hdac1 in ovaries to promote the apoptosis of granulosa cells (GCs), and thus arrested follicular development and delayed sexual maturity. Using porcine GCs as a cell model, a novel sexual maturity-associated lncRNA, which was named as the stimulatory factor of follicular development (), transcribed from mitochondrion and mediated by , was identified using RNA sequencing. Mechanistically, knockdown significantly reduced the H3K27ac level at the -953/-661 region of to epigenetically inhibit its transcription. knockdown released miR-202-3p to reduce the expression of cyclooxygenase 1 (), an essential rate-limited enzyme involved in prostaglandin synthesis. This reduction inhibited the proliferation and secretion of 17β-estradiol (E2) while promoting the apoptosis of GCs. Consequently, follicular development was arrested and sexual maturity was delayed. Taken together, knockdown-mediated downregulation promoted the apoptosis of GCs through the miR-202-3p- axis and lead to delayed sexual maturity. Our findings reveal a novel regulatory network modulated by , and -mediated may be a promising new therapeutic target to treat delayed sexual maturity.
Topics: Animals; Female; Mice; Apoptosis; Cell Proliferation; Cyclooxygenase 1; Granulosa Cells; MicroRNAs; RNA, Long Noncoding; Sexual Maturation; Swine; Histone Deacetylase 1; Hydroxamic Acids
PubMed: 38067162
DOI: 10.3390/cells12232734 -
Journal of Ovarian Research Dec 2023The ovary is an important reproductive organ in mammals, and its development directly affects the sexual maturity and reproductive capacity of individuals. MicroRNAs...
BACKGROUND
The ovary is an important reproductive organ in mammals, and its development directly affects the sexual maturity and reproductive capacity of individuals. MicroRNAs (miRNAs) are recognized as regulators of reproductive physiological processes in various animals and have been shown to regulate ovarian development through typical targeting and translational repression. However, little is known about the regulatory role of miRNAs in ovarian tissue development during sexual maturity in goats. To comprehensively profile the different physiological stages of sexual maturation in goats, we performed small-RNA sequencing of ovarian tissue samples collected at four specific time points (1 day after birth (D1), 2 months old (M2), 4 months old (M4), and 6 months old (M6)). In addition, we used ELISAs to measure serum levels of reproductive hormones to study their temporal changes.
RESULTS
The results showed that serum levels of gonadotropin-releasing hormone, follicle-stimulating hormone, luteinizing hormone, oestradiol, progesterone, oxytocin, and prolactin were lower in goats at the D1 stage than at the other three developmental stages (P < 0.05). The secretion patterns of these seven hormones show a similar trend, with hormone levels reaching their peaks at 4 months of age. A total of 667 miRNAs were detected in 20 libraries, and 254 differentially expressed miRNAs and 3 groups of miRNA clusters that had unique expression patterns were identified (|log2-fold change|> 1, FDR < 0.05) in the 6 comparison groups. RT‒qPCR was employed to confirm that the expression pattern of the 15 selected miRNAs was consistent with the Illumina sequencing results. Gene ontology analyses revealed significant enrichment of GO terms such as cell proliferation regulation, epithelial cell development, and amino acid transport, as well as important signaling pathways including the MAPK signaling pathway, the PI3K-Akt signaling pathway, and the oestrogen signaling pathway. Further miRNA‒mRNA regulation network analysis revealed that 8 differentially expressed miRNAs (chi-miR-1343, chi-miR-328-3p, chi-miR-877-3p, chi-miR-296-3p, chi-miR-128-5p, chi-miR-331-3p, chi-miR-342-5p and chi-miR-34a) have important regulatory roles in ovarian cell proliferation, hormone secretion and metabolism-related biological processes.
CONCLUSIONS
Overall, our study investigated the changes in serum hormone and miRNA levels in the ovaries. These data provide a valuable resource for understanding the molecular regulatory mechanisms of miRNAs in ovarian tissue during the sexual maturity period in goats.
Topics: Humans; Female; Animals; Infant; Goats; Gene Expression Profiling; Phosphatidylinositol 3-Kinases; MicroRNAs; Estradiol
PubMed: 38062510
DOI: 10.1186/s13048-023-01318-8 -
Molecular Psychiatry Feb 2024Puberty is linked to mental health problems during adolescence, and in particular, the timing of puberty is thought to be an important risk factor. This study developed...
Puberty is linked to mental health problems during adolescence, and in particular, the timing of puberty is thought to be an important risk factor. This study developed a new measure of pubertal timing that was built upon multiple pubertal features and their nonlinear changes over time (i.e., with age), and investigated its association with mental health problems. Using the Adolescent Brain Cognitive Development (ABCD) cohort (N ~ 9900, aged 9-13 years), we employed three different models to assess pubertal timing. These models aimed to predict chronological age based on: (i) observed physical development, (ii) hormone levels (testosterone and dehydroepiandrosterone [DHEA]), and (iii) a combination of both physical development and hormones. To achieve this, we utilized a supervised machine learning approach, which allowed us to train the models using the available data and make age predictions based on the input pubertal features. The accuracy of these three models was evaluated, and their associations with mental health problems were examined. The new pubertal timing model performed better at capturing age variance compared to the more commonly used linear regression method. Further, the model based on physical features accounted for the most variance in mental health, such that earlier pubertal timing was associated with higher symptoms. This study demonstrates the utility of our new model of pubertal timing and suggests that, relative to hormonal measures, physical measures of pubertal maturation have a stronger association with mental health problems in early adolescence.
Topics: Humans; Adolescent; Male; Puberty; Child; Female; Testosterone; Mental Health; Dehydroepiandrosterone; Mental Disorders; Sexual Maturation; Cohort Studies; Age Factors
PubMed: 38052980
DOI: 10.1038/s41380-023-02316-4 -
Medicine Dec 2023Central precocious puberty (CPP) is due to the early activation of the hypothalamus-pituitary-gonadal axis, and its incidence is on the rise. A number of studies have... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Central precocious puberty (CPP) is due to the early activation of the hypothalamus-pituitary-gonadal axis, and its incidence is on the rise. A number of studies have shown that nourishing yin and purging fire (NYPF) therapy can be beneficial for CPP. Therefore, we conducted this review to investigate the efficacy, safety, and mechanism of NYPF therapy for CPP.
METHODS
Electronic databases including PubMed, the Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wan-fang Database, and China Scientific Technical Journals Database and 2 platforms including Clinical Trials and Chinese Clinical Trial Registry were searched for randomized controlled trials of NYPF therapy for CPP. A meta-analysis was conducted using RevMan 5.3 and Stata 17.0 software. The core herb pair of NYPF was identified by data mining using IBM SPSS Modeler 18.0 software. The active ingredients and targets of the core herb pair were obtained through the TCMSP database. The main targets of CPP were acquired form the GeneCards, Disgenet and TTD databases. A protein-protein interaction network was carried out to select the core genes by using STRING platform and Cytoscape 3.7.2 software. Metascape platform was used to conduct gene ontology (GO) and KEGG enrichment analysis. The results were verified utilizing molecular docking.
RESULTS
A total of 23 studies were included. Meta-analysis shows the NYPF therapy could significantly improve the clinical efficacy rate and secondary sexual indicators (uterine volume, ovarian volume, breast nucleus diameter, follicular diameter), reduce TCM syndrome scores and serum sex hormone (FSH, LH, E2), and slow down bone age maturation compared to GnRHa therapy group. In addition, NYPF therapy was safe and has no obvious adverse events. Data mining revealed that the core herb pair of NYPF was "Anemarrhenae Rhizoma (Zhimu) - Phellodendri Chinensis Cortex (Huangbai)." Network pharmacology predicted that quercetin, kaempferol, beta-sitosterol, etc were the key components of Zhimu-Huangbai for treating CPP. The core targets were TP53, JUN, AKT1, ESR1, TNF, IL6, CCND1, MAPK1, BCL2, EGFR, IL1B, and PTGS2. They played a pivotal role in modulating multiple signaling pathways, such as Endocrine resistance, MAPK signaling pathway, and PI3K-Akt signaling pathway.
CONCLUSION
This article revealed that NYPF therapy is effective and safe against CPP. The mechanism of the core herb pair of NYPF therapy for CPP through muti-components, muti-targets and muti-pathways.
Topics: Humans; Network Pharmacology; Molecular Docking Simulation; Phosphatidylinositol 3-Kinases; Puberty, Precocious; Asian People; Drugs, Chinese Herbal
PubMed: 38050263
DOI: 10.1097/MD.0000000000036395 -
Cureus Nov 2023Genitourinary syndrome of menopause (GSM) is a progressive condition due to a hypoestrogenic state affecting perimenopausal and menopausal women. GSM was previously... (Review)
Review
Genitourinary syndrome of menopause (GSM) is a progressive condition due to a hypoestrogenic state affecting perimenopausal and menopausal women. GSM was previously known as urogenital syndrome, vulvovaginal atrophy, or atrophic vaginitis. The term vulvovaginal atrophy did not encompass the symptoms of the urinary tract like incontinence, urgency, and discomfort, or allude that it is due to a hypoestrogenic state. Although a significant segment of the population is affected by GSM, it is very sparsely studied, detected, and treated. GSM affects the quality of life and sexual health of most menopausal women suffering from it. Only a few healthcare providers ask about the symptoms of GSM and a tiny percentage of women seek consultation for it. This may be because they are either embarrassed or believe it to be a part of the natural process of aging. As the life expectancy of women has increased in general, the prevalence of GSM has also risen, while it still remains underdiagnosed and untreated. Properly educating women so that they can seek consultation regarding symptoms of GSM, and training healthcare professionals about communicating with the patient, as well as correctly identifying, diagnosing, and managing the patient are all important to overcome this communication barrier. Once we cross the barrier of diagnosing patients with GSM, we still have to manage the patients with tailor-made prescriptions according to the severity of the symptoms and their preferences. While there are various treatment options, the most effective one is low-dose topical estrogen therapy. In this review, we intend to explore the existing knowledge about GSM and its effect on the quality of life and sexual health of women along with the treatment options for managing and reversing the effects of GSM.
PubMed: 38046779
DOI: 10.7759/cureus.48143 -
Journal of the Endocrine Society Dec 2023Serum prolactin (PRL) levels exhibit a gradual rise both in male and female rats from birth to adulthood, with females consistently displaying higher levels compared to... (Review)
Review
Serum prolactin (PRL) levels exhibit a gradual rise both in male and female rats from birth to adulthood, with females consistently displaying higher levels compared to age-matched males. This pattern has traditionally been attributed to the development and maturation of endocrine and neuroendocrine networks responsible for regulating PRL synthesis and secretion. However, the effect of dopamine (DA), which acts as an inhibitory factor on lactotroph function, also increases from birth to puberty, particularly in females. Nonetheless, the secretion of PRL remains higher in females compared to males. On the other hand, the observed sex differences in serum PRL levels during early postnatal development cannot be attributed to the influence of estradiol (E2). While serum E2 levels gradually increase after birth, only after 45 days of life do the disparities in E2 levels between females and males become evident. These observations collectively suggest that neither the maturation of hypothalamic DA regulation nor the rise in E2 levels can account for the progressive and sustained elevation in serum PRL levels and the observed sexual dimorphism during postnatal development. This review highlights the importance of recent discoveries in animal models that shed light on inhibitory mechanisms in the control of PRL secretion within the pituitary gland itself, that is intrapituitary mechanisms, with a specific emphasis on the role of transforming growth factor β1 and activins in PRL secretion.
PubMed: 38045876
DOI: 10.1210/jendso/bvad146 -
Evolutionary Applications Nov 2023Adaptation to captivity in spawning programs can lead to unintentional consequences, such as domestication that results in reduced fitness in the wild. The timing of...
Adaptation to captivity in spawning programs can lead to unintentional consequences, such as domestication that results in reduced fitness in the wild. The timing of sexual maturation has been shown to be a trait under domestication selection in fish hatcheries, which affects a fish's access to mating opportunities and aligning their offspring's development with favorable environmental conditions. Earlier maturing fish may be favored in hatchery settings where managers provide artificially optimal growing conditions, but early maturation may reduce fitness in the wild if, for example, there is a mismatch between timing of reproduction and availability of resources that support recruitment. We investigated patterns of maturation timing in a delta smelt () conservation hatchery by quantifying changes to the median age at maturity since the captive spawning program was initiated in 2008. Over the span of a decade, we observed a small, but significant increase in age at maturity among broodstock by 2.2 weeks. This trait had low heritability and was largely controlled by phenotypic plasticity that was dependent on the time of year fish were born. Fish that were born later in the year matured faster, potentially a carryover from selection favoring synchronous spawning in the wild. However, higher DI (domestication index) fish showed a loss of plasticity, we argue, as a result of hatchery practices that breed individuals past peak periods of female ripeness. Our findings suggest that the hatchery setting has relaxed selection pressures for fish to mature quickly at the end of the year and, consequently, has led to a loss of plasticity in age at maturity. Hatchery fish that are re-introduced in the wild may not be able to align maturation with population peaks if their maturation rates are too slow with reduced plasticity, potentially resulting in lower fitness.
PubMed: 38029063
DOI: 10.1111/eva.13611 -
Frontiers in Endocrinology 2023fish exhibit a clear phenotypic polymorphism in puberty onset and reproductive strategies of males. In and , puberty onset is genetically determined and linked to a...
fish exhibit a clear phenotypic polymorphism in puberty onset and reproductive strategies of males. In and , puberty onset is genetically determined and linked to a melanocortin 4 receptor (Mc4r) polymorphism of wild-type and mutant alleles on the sex chromosomes. We hypothesized that Mc4r mutant alleles act on wild-type alleles by a dominant negative effect through receptor dimerization, leading to differential intracellular signaling and effector gene activation. Depending on signaling strength, the onset of puberty either occurs early or is delayed. Here, we show by Förster Resonance Energy Transfer (FRET) that wild-type Mc4r monomers can form homodimers, but also heterodimers with mutant receptors resulting in compromised signaling which explains the reduced Mc4r signaling in large males. Thus, hetero- homo- dimerization seems to be the key molecular mechanism for the polymorphism in puberty onset and body size in male fish.
Topics: Animals; Male; Dimerization; Receptor, Melanocortin, Type 4; Sexual Maturation; Polymorphism, Genetic; Body Size
PubMed: 38027153
DOI: 10.3389/fendo.2023.1267590 -
Royal Society Open Science Nov 2023The primary (PSR), secondary (SSR) and adult (ASR) sex ratios of sexually reproducing organisms influence their life histories. Species exhibiting reversed sexual size...
The primary (PSR), secondary (SSR) and adult (ASR) sex ratios of sexually reproducing organisms influence their life histories. Species exhibiting reversed sexual size dimorphism (RSD) may imply a higher cost of female production or lower female survival, thus generating biases in PSR, SSR and/or ASR towards males. The Harpy Eagle is the world's largest eagle exhibiting RSD. This species is found in the Neotropical region and is currently threatened with extinction. We used molecular markers to determine the sex of 309 Harpy Eagles spanning different life stages-eaglets, subadults and adults-from 1904 to 2021 within the Amazon Rainforest and Atlantic Forest. Sex ratios for all life stages revealed a female-biased deviation across all periods and regions. Our results suggest that the population bias towards females is an evolutionary ecological pattern of this species, and SSR and ASR likely emerged from the PSR. This natural bias towards females may be compensated by an earlier sexual maturation age of males, implying a longer reproductive lifespan and a higher proportion of sexually active males. A better understanding of the Harpy Eagle's life history can contribute to understanding sex-role evolution and enable more appropriate conservation strategies for the species.
PubMed: 38026037
DOI: 10.1098/rsos.231443