Search Results (59)

Background: Prolactin receptor (PRLR) signaling affects breastfeeding and potentially breast cancer treatment response. Methods: The prognostic impact of 20 PRLR single nucleotide polymorphisms (SNPs) in relation to adjuvant treatment groups in patients with primary breast cancer (n = 1701, 2002–2016, Sweden) was evaluated. Genomic DNA was genotyped on Illumina OncoArray, and survival analyses with up to 15-year follow-up were performed. Interaction models, adjusted for potential confounders, were created with different adjuvant treatment modalities: chemotherapy, radiotherapy, tamoxifen, and aromatase inhibitors. Results: Five SNPs (rs7734558, rs6860397, rs2962101, rs7732013, and rs4703503) showed interactions with radiotherapy and were utilized to create seven combined genotypes: six unique and one ‘rare’. Patients carrying combined genotype AG/GG/TT/CC/TC or ‘rare’ combinations derived greater benefits from radiotherapy than other patient groups (both HR_adj ≤ 0.29, Bonferroni-adjusted P_int ≤ 0.039). Expression Quantitative Trait Loci (eQTL) analysis revealed that three PRLR SNPs were associated with decreased PRLR expression. To explore potential SNP-associated effects, gene expression and transcriptional networks were analyzed in the METABRIC cohort and indicated that PRLR-low tumors were associated with reduced DNA repair signaling and enhanced anti-tumoral immunity. Conclusions: PRLR merits further evaluation as a putative pharmacogenomic biomarker in relation to radiotherapy for breast cancer patients. Full article

Caprine arthritis and encephalitis (CAE), caused by small ruminant lentivirus (SRLV), is a key disease of goats, with chronic inflammation of joints and brain symptoms leading to losses in milk production and animal trade. In this study, we analyzed gene expressions in the milk somatic cells (MSCs) of seropositive (SRLV-SP) and seronegative (SRLV-SN) goats to identify transcriptomic changes using a non-invasive sampling method. Materials and Methods: This study was conducted on goats of two Polish breeds (Polish Improved White and Polish Improved Fawn), which were kept at the Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, during their first lactation. MSCs were isolated from milk, and gene expression was analyzed using the Goat Gene Expression Microarray. The results were verified by RT-qPCR for five genes (DUSP26, PRLR, SCARA3, APBB2, OR4F4). Statistical analysis was performed in GeneSpring 12 software. Results: Microarrays showed reduced expression of DUSP26, PRLR, SCARA3, APBB2, and OR4F4 genes in SRLV-SP goats. RT-qPCR confirmed changes for DUSP26, SCARA3, and APBB2. Functional analysis indicated associations with immune processes and HIV-like pathways. Discussion: The results suggest that SRLV induces transcriptomic perturbations, especially in immunity-related genes. MSCs are an effective model for non-invasive studies, and further studies may support strategies for combating CAE. Full article

Background: Prolactin (PRL) is a key reproductive hormone that regulates follicular development through endocrine and paracrine mechanisms. However, its specific role in porcine follicular development remains unclear. Methods: In the in vivo experiments, follicular fluid and tissue cells were obtained from small (1–2 mm), medium (3–4 mm), and large (5–6 mm) porcine follicles. PRL levels in follicular fluid were measured by ELISA. The expression levels of genes and proteins related to follicular development were assessed using quantitative real-time PCR (RT-qPCR) and Western blotting (WB). In the in vitro experiments, CCK-8, RT-qPCR, and WB were used to detect the effects of different concentrations (0, 30, and 300 ng/mL) of recombinant porcine prolactin (prPRL) on granulosa cell (GC) proliferation, steroid hormone synthesis, and angiogenesis, and transcriptome sequencing was performed. Results: The PRL concentration was significantly higher in large follicles compared to small and medium follicles. During follicular development, expression levels of PRL, PRL receptor (PRLR), proteolytic enzymes (CTSD, MMP2, MMP14, and BMP-1), and angiogenic factors (VEGFA and FGF-2) increased and then decreased. Moreover, prPRL promoted GC proliferation, increased the expression of PCNA and cyclin D1, upregulated steroidogenesis-related genes CYP11A1 and 3β-HSD, and significantly enhanced the expression of key angiogenic factors VEGFA and FGF-2. RNA-seq analysis identified 226 differentially expressed genes (DEGs), which were mainly enriched in signaling pathways such as the Hippo, JAK/STAT, and Rap1 pathways. Conclusions: PRL may regulate porcine follicle development by affecting cell proliferation and angiogenesis in GCs through the Hippo, JAK/STAT and Rap1 signaling pathways. Full article

Per- and polyfluoroalkyl substances (PFAS) are used in consumer products and manufacturing. Perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) are long-chain PFAS composed of 9, 10, and 11 carbons, respectively, which exert sublethal toxicity to aquatic species. Here, we review the data regarding the environmental fate and ecotoxicology of these understudied long-chain PFAS in fish. The objectives of this study were to (1) compile the literature to compare physiological or molecular signaling pathways disrupted by PFNA, PFDA, or PFUnDA; and (2) uncover potential biomarkers and pathways of toxicity of longer-chain PFAS using gene ontology computational approaches to shed light on their mechanism of action. Studies show that PFAS have a range of effects on fish, including developmental issues, changes in gene expression, and behavioral modifications. Based on our review, PFNA has been studied more frequently in fish compared to PFDA and PFUnDA; however, longer-chained PFAS are proposed to pose greater toxicity. Based on the computational approach, prominent pathways affected by PFNA include insulin signaling [“Insulin -> CEBPA/CTNNB/FOXA/FOXO”, “Insulin -> STAT Expression Targets”], immune system signaling [“TNF -> STAT Expression Targets”, “IL6 Expression Targets”, and “IL2 Expression Targets”], and growth hormone/prolactin signaling [“GH1/PRLR Expression Targets”, “PRL/GHR -> STAT Expression Targets”, “PRL/PRLR Expression Targets”]. Several transcripts related to cholesterol metabolism were also affected by PFNA. This review summarizes the current knowledge on the distribution, fate, and ecotoxicology of PFNA, PFDA, and PFUnDA in teleost fish, highlighting potential physiological and molecular responses that could aid in assessing long-chain PFAS toxicity in future studies. Full article

Prolactin is a hormone for which actions on the central nervous system such as neurogenesis and neuroprotection have been described by acting on specific receptors. The presence of prolactin receptors in the brain, including the hippocampus, is well documented; however, it is unknown whether these receptors change with age and whether they are related to sex. For this reason, a study of the expression of prolactin receptors, in the short and long isoforms, in the hippocampus of male and female rats has been carried out by qPCR and in situ hybridization, with a densitometric analysis in the following life stages: prepubertal, postpubertal, young adult, adult, and old. The results revealed the greater expression of the long isoform than of the short isoform in males, but not in females, with significant differences between males and females and in the different life stages studied. With significant differences, the highest expression of both isoforms appeared in male rats in the postpubertal stage, and the lowest expression was observed in adult and old animals. In situ hybridization showed differences in the localization of PRLR mRNA expression in CA1, CA3, and DG depending on the age and sex of the rats. The results obtained suggest that hippocampal aging is related to a decrease in prolactin receptors, which helps to better understand brain aging. Full article

Strong broodiness is an important reproductive characteristic of Magang geese, manifested by periodic laying–incubation activities during the breeding season. To investigate the changes in ovarian activity, follicular development, and gonadal reproductive regulators during the laying–incubation cycle, this study examined ovarian morphology, follicular development, blood reproductive hormones, and the expressions of reproductive regulators in the gonadal stroma, follicular granulosa, and membranous layer of the follicles during the laying, early broodiness, depth of broodiness, and end of broodiness periods of Magang geese. The results showed that ovarian activity degenerated and atrophied with the onset of brooding: the number of LWFs and SYFs decreased rapidly; LFY disappeared; PRL in the blood increased significantly; FSH, P4, E2, and INH decreased significantly; and the mRNA levels of GnIH and steroidogenic factors were up-regulated in the ovarian stroma. With the termination of brooding, the ovarian activity was gradually restored: the numbers of LWFs and SYFs increased gradually; LYF began to appear; PRL in the blood decreased; FSH and E2 increased; P4 remained low; and expressions of GnIH and steroidogenic factors were down-regulated in the ovarian stroma. During the laying period, with the rapid development of follicles, the expressions of FSHR and GnIH were significantly up-regulated; GnIH expression peaked in the SY granulosa layer, while FSHR expression peaked in the F6 granulosa layer. As LYF developed and ovulation occurred, the expressions of FSHR and GnIH were significantly down-regulated, LHR expression was significantly up-regulated, the expression of GnIHR peaked in the F3 granulosa layer and then declined, PRLR expression was the lowest in the F1 granulosa layer, steroidogenic factor StAR was up-regulated, CYP19A1 was down-regulated, and 3β-HSD peaked in the F3 granulosa layer and then declined. The results indicate that GnIH/GnIHR, FSHR, LHR, and PRLR in the gonad correspond to the upstream reproductive hormones and the jointly regulated steroid hormone production and follicular development, which leads to periodic changes in ovarian activity during the laying–incubation cycle of the breeding season of Magang geese. GnIH/GnIHR might play an important regulatory role for FSHR, LHR, and PRLR in the gonads. Full article

A study was designed to explore the possibility of using herbal supplementation to sustain growth performance during heat stress exposure in Kenguri sheep. This 60-day study was conducted on 24 Kenguri ewes (1–2 years old), randomly assigned to four treatment groups (n = 6 per group) as follows: KC (n = 6; Kenguri Control), KHS (n = 6; Kenguri Heat Stress), KCS (n = 6; Kenguri Control and herbal supplement), and KHSS (n = 6; Kenguri Heat Stress and herbal supplement). The herbal mixture of Ocimum sanctum (Tulsi), Emblica officinalis (Amla), Morinda citrifolia (Noni), Withania somnifera (Ashwagandha), and Phyllostachys edulis (Bamboo) was used in this study. The herbal supplement used in the present study was given to the KCS and KHSS groups’ animals in dry powder form at a dose of 0.8 g/Kg BW/Day. All variables were recorded fortnightly, and gene expression analysis was performed at the end of the experiment. The results indicated that the recorded temperature–humidity index (THI) provided thermal comfort for KC and KCS while inducing extremely severe heat stress to the KHS and KHSS groups. Heat stress did not alter the feed intake, while the herbal supplement during heat stress increased the feed intake from day 30 onwards. Furthermore, heat stress significantly (p < 0.001) increased the water intake, while the herbal supplement did not alter the heat stress-induced water intake. In addition, neither heat stress nor herbal supplements influenced the body weight and allometric measurements studied. Furthermore, heat stress significantly (p < 0.01) decreased the level of plasma tri-iodo-thyronine (T₃) and thyroxin (T₄) and had a non-significant effect on plasma growth hormone (GH), insulin-like growth factor-1 (IGF-1), while the herbal supplements significantly (p < 0.01) increased the levels of all these hormones studied. Likewise, in peripheral blood mononuclear cells (PBMCs) the expression patterns of growth hormone receptor (GHR), Insulin-like growth factor 1 (IGF1) and prolactin receptor (PRLR) were significantly (p < 0.001) downregulated during heat stress (0.25, 0.3, and 0.48-fold change, respectively). However, the herbal supplement significantly (p < 0.01) increased the heat stress-induced reduction in the expression pattern of these three genes (0.65, 0.61, and 0.61-fold change, respectively). Therefore, from this study, it could be concluded that although the herbal supplements did not bring positive changes in body weight and allometric measurements, it still had a beneficial impact on the endocrinology and genes governing growth performance in Kenguri ewes. Thus, the herbal feed additive used in the study shows promise for relieving heat stress in Kenguri ewes. Full article

Prolactin (PRL) regulates its own secretion by short-loop feedback to tuberoinfundibular dopaminergic (TIDA) neurons. PRL-induced cellular mechanisms in the regulation of tyrosine hydroxylase (TH) are not completely understood. The objectives were to (1) examine PRL-induced, time-dependent hypothalamic changes in JAK2-STAT5B signaling, TH activity, TH phosphorylation state and Th mRNA levels, and (2) evaluate direct influences of PRLR-STAT5B signaling on Th promoter activity. Ovariectomized rats were administered ovine PRL. JAK2 and STAT5 phosphorylation in the mediobasal hypothalamus peaked at 15 and 30–60 min, respectively. TH Ser40 phosphorylation in the median eminence was increased between 2 and 72 h, correlating with increased dihydroxyphenylalanine (DOPA) accumulation. Th mRNA levels in TIDA neurons were unchanged up to 72 h but elevated by 7 days. PRL did not alter Th promoter activity in CAD cells, and STAT5B did not bind three putative Gamma Interferon Activation Sites (GAS) elements. We conclude that PRL initiates an integrated cascade of cellular mechanisms in TIDA neurons, including JAK2-STAT5B activation, TH Ser40 phosphorylation coupled to increased TH activity, followed by a delayed rise in Th gene expression. PRL-induced changes in Th gene expression are not the result of STAT5-mediated transactivation but likely result from enduring changes in TIDA neuronal activity. Full article

This study designed three sgRNAs (sgRNA139, sgRNA128, and sgRNA109) targeting the prolactin gene receptor (PRLR) in fetal cattle, utilized Cas9 to cleave endogenous DNA, and screened stable cell lines for somatic cell nuclear transfer experiments to investigate the impact of different editing sites on embryonic development. The results showed that sgRNA139 had the highest cleavage efficiency (Fcut = 0.65, Indels = 42.19%), while sgRNA109 had the lowest (Fcut = 0.45, Indels = 35.31%). No significant differences were observed in cell growth status after electroporation (p > 0.05), and the transfection efficiency exceeded 90% after five days of culture. In the evaluation of key embryonic development indicators, sgRNA109 significantly reduced the cleavage rate and blastocyst rate (p < 0.01), whereas sgRNA139 showed no significant effect on the cleavage rate (p > 0.05), but its blastocyst rate was slightly lower than that of the control group (p > 0.05). This study demonstrates that highly specific sgRNAs and stable edited cell lines used as donor cells can significantly regulate the later stages of embryonic development. This study not only provides new experimental evidence for the functional study of the PRLR but also lays an important theoretical foundation for the innovation of molecular breeding technologies in dairy cattle. Full article

The hypothalamus (hyp) serves as the regulatory hub of the neuroendocrine system, synthesizing and secreting reproductive hormones that modulate estrus, follicular maturation, and embryonic development in goats. This study employed RNA-seq analysis to examine gene expression in the hypothalamic tissue of Yunshang black goats during the luteal phase in goats with high fecundity (LP_HY), during the luteal phase in goats with low fecundity (LP_LY), during the follicular phase in goats with high fecundity (FP_HY), and during the follicular phase in goats with low fecundity (FP_LY). Differential long non-coding RNAs (DE lncRNAs) and differential mRNAs (DE mRNAs) were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and the construction of co-expression networks associated with reproduction. As a result, DE lncRNAs (390, 375, 405, and 394) and DE mRNAs (1836, 2047, 2003, and 1963) were identified in the four comparisons, namely FP_LY vs. FP_HY, LP_HY vs. FP_HY, LP_LY vs. FP_LY, and LP_LY vs. LP_HY, respectively. Functional annotations indicated significant enrichment of numerous DE lncRNAs and DE mRNAs in reproduction-related pathways such as the gonadotropin-releasing hormone pathway, the prolactin signaling pathway, the estrogen signaling pathway, the Wnt signaling pathway, oocyte meiosis, and progesterone-mediated oocyte maturation. The co-expression network of lncRNAs and target genes identified the interrelationships between reproduction-related genes such as IGF1, PORCN, PLCB2, MAPK8, PRLR, and CPEB2 with our newly discovered lncRNAs. This study expands the understanding of lncRNAs and mRNAs in goat hypothalamic tissue and provides new insights into molecular mechanisms related to goat reproduction. Full article

Medicinal plants and natural compounds have been considered alternative therapeutic options for counteracting postmenopausal disorders thanks to their different concomitant effects, including antioxidant and anti-inflammatory properties and the regulation of hormone activity. It is important to highlight that the efficacy of medicinal plants and natural compounds increases when used in combination, thus making the development of herbal formulations rational. Therefore, the present study aimed to evaluate the phytochemical and pharmacological properties of an innovative formulation consisting of resveratrol and water extracts from Equisetum arvense, Crateagus curvisepala, Vitex agnus-castus, and Glycine max. The phenolic composition and radical scavenger properties were evaluated using chromatographic and colorimetric (ABTS) methods, whilst the limits of biocompatibility were assessed through allelopathy, the Artemia salina (brine shrimp) lethality test, and Daphnia magna cardiotoxicity assay. The protective effects were evaluated on C2C12 cell lines exposed to the pro-oxidant stimulus, which consisted of hydrogen peroxide. The gene expression of estrogen 1 (ESR1, also known as ERα) and prolactin (PRLR) receptors, interleukin 6 (IL-6), tumor necrosis factor α (TNFα), and receptor activator of nuclear factor kappa-Β ligand (RANKL) was measured. The results of the phytochemical analysis showed that the main phytochemicals were hydroxycinnamic and phenolic acids, in particular coumaric acid (7.53 µg/mL) and rosmarinic acid (6.91 µg/mL), respectively. This could explain the radical scavenger effect observed from the 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay. According to the ecotoxicological models’ results, the formulation was revealed to be non-toxic, with a LC₅₀ value > 1 mg/mL. Therefore, a biocompatible concentration range (200–1000 µg/mL) was used in C2C12 cells, where the formulation blunted the hydrogen peroxide-induced upregulation of TNFα, IL-6, RANKL, ESR1, and PRLR. Overall, the results of this study corroborate the use of the formulation for facing the oxidative stress and inflammation, which forms the basis of the osteoclastogenic process. Full article

In our previous study, we found that changes in plasma prolactin (PRL) concentration were significantly associated with heat stress in dairy cows, and that PRL plays an important role in milk performance. Microarray sequencing revealed that thyrotropin releasing hormone (TRH) and prolactin receptor (PRLR), two genes important for PRL expression or function, may affect milk performance, reproduction, and heat stress response in dairy cattle. In this study, we further validated the genetic effects of the three genes in Chinese Holsteins. The potential variants within the three genes were first detected in 70 Chinese Holstein bulls and then screened in 1152 Chinese Holstein cows using the KASP (Kompetitive allele-specific PCR) method. In total, 42 variants were identified. Further, 13 SNPs were retained for KASP genotyping, including 8 in TRH, 3 in PRL, and 2 in PRLR. Using SNP-based association analyses, the multiple significant (p < 0.05) associations of these 13 SNPs with milk performance, reproduction, and heat stress response traits were found in the Holstein population. Furthermore, linkage disequilibrium analysis found a haplotype block in each of the TRH and PRL genes. Haplotype-based association analyses showed that haplotype blocks were also significantly (p < 0.05) associated with milk performance, reproduction, and heat stress response traits. Collectively, our results identified the genetic associations of TRH, PRL, and PRLR with milk performance, reproduction, and heat stress response traits in dairy cows, and found the important roles of SNP g.55888602A/C and g.55885455A/G in TRH in all traits, providing important molecular markers for genetic selection of high-yielding dairy cows. Full article

Background/Objectives: We have previously identified let-7f-5p, miR-10b-5p, miR-34a-5p, miR-181b-5p, and miR-181d-5p as differentially expressed between uterine leiomyoma (LM) and leiomyosarcoma (LMS) tissue samples. The present study aimed to characterize these miRNA expression profiles and to assess the functional role of miR-34a and miR-181b in uterine LM and LMS cells. Methods: All the selected miRNAs showed downregulation in LMS cells compared to LM cells, but only miR-34a and miR-181b expression patterns matched those of patient samples. Therefore, these two miRs were selected for further analyses. Results: Loss of function analysis demonstrated that miR-34a and miR-181b silencing inhibited LM cell proliferation and migration. MiR-34a silencing induced CCND1 and MDM4 expression and inhibited KMT2D, BCL2, and NOTCH2 in LM. Silencing of miR-181b promotes TIMP3 and FGFR1 expression in LM and diminishes BCL2, NOTCH2, ATM, IRS1, and PRLR. Gain of function analysis revealed that the introduction of miR-34a and miR-181b mimics suppressed proliferation and migration in malignant LMS cells. Additionally, transfection with a miR-34a mimic downregulated NOTCH2 and BCL2 expression and enhanced the expression of CCND1, KMT2D, and TP53 in LMS cells. Moreover, miR-181b overexpression decreased TIMP3, NOTCH2, ATM, and IRS1 expression and increased the expression of FGFR1 in this cell. Importantly, the single introduction of either a miR-34a or miR-181b mimic was able to decrease the invasion capacity of LMS cells. Conclusions: Our studies demonstrated that miR-34a or miR-181b may play an anti-oncogenic role in uterine tumors; further studies are needed to better understand the role and regulatory mechanism of these miRNAs in LMS cancer development, which will help provide prognostic and therapeutic options for patients with LMS. Full article

The Chinese tongue sole (Cynoglossus semilaevis) is a marine flatfish of significant economic value, characterized by pronounced female-biased sexual size dimorphism (SSD). Sexual differences of cell number and gene expression within the PIT-1 lineage of the pituitary gland may be crucial for interpreting the female-biased SSD of C. semilaevis. Among hormones secreted by PIT-1 cell lineage, growth hormone (gh), prolactin (prl), prolactin 2 (prl2), and somatolactin (sl) comprise a gene family within the extensive superfamily of class-1 helical cytokines. To better understand the function of the gh/prl/sl in teleost SSD, we firstly identified five genes of the gh/prl/sl family (gh, sl, prl, prl2a, and prl2b) and their receptors (ghra, ghrb, prlra, prlrb, and prlr-like) from C. semilaevis at the genome-wide level. Phylogenetic analyses revealed that the gh/prl/sl family and their receptors were each clustered into five distinct groups. More microsatellites were revealed in the intron 2 of gh gene of female rather than the male and pseudo-male individuals, which is positively correlated with its sexual expression pattern. Interaction network prediction indicated that gh, prl, and sl may collectively contribute to individual growth and development. A FRET experiment showed that ghra can act as a receptor for sl. Additionally, the transcripts of the gh/prl/sl family and their receptors exhibited varying abundances in the pituitary, brain, gonad, and liver of both female and male C. semilaevis, with most ligands showing the highest abundance in the female pituitary. Furthermore, gh and sl were found to be maternally expressed. The knock-down of gh, prl, and sl in the pituitary cells could lead to the expression change of igf1, c-fos, and sos2. This study provided a foundation for further functional characterization of the gh/prl/sl gene family, contributing to a deeper understanding of the growth and reproductive mechanisms in C. semilaevis. Full article

Breast cancer (BC) is the most common cancer in women, and a higher level of prolactin-induced protein (PIP) is associated with better responses to adjuvant chemotherapy. The signal transducer and activator of transcription 5 (STAT5) is a potential regulator of the PIP gene. Prolactin (PRL) and its receptor (PRLR) activate JAK2/STAT5 signaling in BC, which is modulated by inhibitors like suppressors of cytokine signaling (SOCS) proteins and protein inhibitors of activated STAT (PIAS). Using real-time PCR and immunohistochemistry, we studied the relationship between PIP and STAT5 inhibitors in BC. Our findings indicated that PIP and STAT5 levels decrease with a higher tumor grade, size, and tumor/nodes/metastasis (TNM) clinical stage, while nuclear PIAS3 levels increase with tumor progression. Both STAT inhibitors are linked to estrogen and progesterone receptor status. Notably, STAT5 correlates positively with PIP, SOCS3, and PIAS3, suggesting that it may be a favorable prognostic factor. Among the STAT inhibitors, only nuclear PIAS3 expression correlates with PIP. In vitro studies indicated that silencing PIAS3 in T47D cells does not affect PIP expression or sensitivity to doxorubicin (DOX), but T47D control cells with a higher PIP expression are more sensitive to DOX, highlighting the need for further investigation into these mechanisms. Full article