Reproduction, Fertility, And Development[JOURNAL]
Sun
200 papers
Effect of arachidonic acid on pre- and post-hatching bovine embryo development.
González-Brusi L, Pérez-Gómez A, Quiroga AC … +3 more , Tamargo C, Ramos-Ibeas P, Bermejo-Álvarez P
Reprod Fertil Dev · 2023 Jul · PMID 37430407 · Publisher ↗
CONTEXT: Arachidonic acid (AA) is the precursor of prostaglandins, which may play autocrine roles during early embryo development. AIMS: To test the developmental effects of addition of AA to pre- and post-hatching cultu...
CONTEXT: Arachidonic acid (AA) is the precursor of prostaglandins, which may play autocrine roles during early embryo development. AIMS: To test the developmental effects of addition of AA to pre- and post-hatching culture media on in vitro -produced bovine embryos. METHODS: Pre-hatching effects of AA were tested by culturing bovine zygotes in synthetic oviductal fluid (SOF) supplemented with 100 or 333μM AA. Post-hatching effects of AA were tested by culturing Day 7 blastocysts in N2B27 supplemented with 5, 10, 20 or 100μM AA up to Day 12. KEY RESULTS: Pre-hatching development to blastocyst was completely abrogated at 333μM AA, whereas blastocyst rates and cell numbers were not altered at 100μM AA. Impaired post-hatching development was observed at 100μM AA, whereas no effect on survival rates was noted at 5, 10 and 20μM AA. However, a significant reduction in Day 12 embryo size was observed at 10 and 20μM AA. Hypoblast migration, epiblast survival and formation of embryonic-disc-like structures were unaffected at 5-10μM AA. AA exposure downregulated the genes PTGIS , PPARG , LDHA and SCD in Day 12 embryos. CONCLUSIONS: Pre-hatching embryos are mostly irresponsive to AA, whereas AA was observed to have negative effects during early post-hatching development. IMPLICATIONS: AA does not improve in vitro bovine embryo development and is not required up to early post-hatching stages.
Extremely low-frequency electromagnetic field exposure alters DNA methylation levels in the endometrium of pigs during the peri-implantation period.
Wydorski PJ, Kozlowska W, Drzewiecka EM … +2 more , Zmijewska A, Franczak A
Reprod Fertil Dev · 2023 Jul · PMID 37400364 · Publisher ↗
CONTEXT: Extremely low-frequency electromagnetic field (ELF-EMF) emission is increasing due to substantial technological progress. The results of previous research provided evidence that ELF-EMF may exert changes in mole...
CONTEXT: Extremely low-frequency electromagnetic field (ELF-EMF) emission is increasing due to substantial technological progress. The results of previous research provided evidence that ELF-EMF may exert changes in molecular mechanisms that control female reproduction. AIMS: We hypothesised that short-term ELF-EMF treatment alters the DNA methylation level of genes in the endometrium. Hence, the research aimed to determine the methylation level of selected genes whose expression was altered in response to ELF-EMF radiation in the endometrium of pigs during the peri-implantation period (days 15-16 of pregnancy). METHODS: Porcine endometrial slices (100±5mg) were collected during the peri-implantation period and exposed to ELF-EMF at a frequency of 50Hz for 2h in vitro . The control endometrium was not exposed to ELF-EMF. The level of DNA methylation in the promoter regions of EGR2 , HSD17B2 , ID2 , IL1RAP, MRAP2, NOS3, PTGER4, SERPINE1, VDR and ZFP57 was tested using qMS-PCR. KEY RESULTS: In the endometrium exposed to ELF-EMF, the level of methylation of HSD17B2 , MRAP2 , SERPINE1, VDR and ZFP57 was not altered; the level of methylation of EGR2 , ID2 and PTGER4 increased, and the level of methylation of IL1RAP and NOS3 decreased. CONCLUSIONS: ELF-EMF may alter the level of DNA methylation in the endometrium during the peri-implantation period. IMPLICATIONS: Changes in the DNA methylation induced by ELF-EMF may affect the transcriptomic profile of the endometrium and disturb physiological processes accompanying implantation and embryo development.
Increased DNA strand breaks in spermatozoa of knockout mice.
Pawlicka B, Duliban M, Zieba M … +6 more , Bochenek M, Zieba K, Adham I, Studencka-Turski M, Meinhardt A, Grzmil P
Reprod Fertil Dev · 2023 Jul · PMID 37393946 · Publisher ↗
CONTEXT: The Pxt1 gene encodes a male germ cell-specific protein and its overexpression results in male germ cell degeneration and male infertility in transgenic mice. AIMS: The analysis of the function of Pxt1 during mo...
CONTEXT: The Pxt1 gene encodes a male germ cell-specific protein and its overexpression results in male germ cell degeneration and male infertility in transgenic mice. AIMS: The analysis of the function of Pxt1 during mouse spermatogenesis. METHODS: The phenotype of Pxt1 knockout mice was characterised by testicular histology, assessment of semen parameters including sperm motility, and DNA fragmentation by flow cytometry. Gene expression was analysed using RT-PCR. Fertility of mutants was checked by standard breeding and competition breeding tests. KEY RESULTS: In Pxt1 -/- mice, a strong increase in the sperm DNA fragmentation index (DFI) was observed, while other sperm parameters were comparable to those of control animals. Despite enhanced DFI, mutants were fertile and able to mate in competition with wild type males. CONCLUSIONS: Pxt1 induces cell death; thus, the higher sperm DFI of mice with targeted deletion of Pxt1 suggests some function for this gene in the elimination of male germ cells with chromatin damage. IMPLICATIONS: Ablation of mouse Pxt1 results in enhanced DFI. In humans, the homologous PXT1 gene shares 74% similarity with the mouse gene; thus, it can be considered a candidate for mutation screening in patients with increased DFI.
Cytokine supplemented maturation medium improved development to term following somatic cell nuclear transfer (SCNT) in cattle.
Keim J, Liu Y, Regouski M … +4 more , Stott R, Singina GN, White KL, Polejaeva IA
Reprod Fertil Dev · 2023 Jul · PMID 37308165 · Publisher ↗
CONTEXT: In vitro maturation is an important process in the production of embryos. It has been shown that three cytokines, fibroblast growth factor 2, leukemia inhibitory factor and insulin-like growth factor 1 (FLI), in...
CONTEXT: In vitro maturation is an important process in the production of embryos. It has been shown that three cytokines, fibroblast growth factor 2, leukemia inhibitory factor and insulin-like growth factor 1 (FLI), increased efficiency of in vitro maturation, somatic cell nuclear transfer (SCNT) blastocyst production, and in vivo development of genetically engineered piglets. AIMS: Assess effects of FLI on oocyte maturation, quality of oocytes, and embryo development in bovine in vitro fertilisation (IVF) and SCNT. KEY RESULTS: Cytokine supplementation resulted in significant increases in maturation rates and decreased levels of reactive oxygen species. Oocytes matured in FLI had increased blastocyst rates when used in IVF (35.6%vs 27.3%, P <0.05) and SCNT (40.6%vs 25.7%, P <0.05). SCNT blastocysts contained significantly more inner cell mass and trophectodermal cells when compared to the control group. Importantly, SCNT embryos derived from oocytes matured in FLI medium resulted in a four-fold increase in full-term development compared to control medium (23.3%vs 5.3%, P <0.05). Relative mRNA expression analysis of 37 genes associated with embryonic and fetal development revealed one gene had differential transcript abundance in metaphase II oocytes, nine genes at the 8-cell stage, 10 genes at the blastocyst stage in IVF embryos and four genes at the blastocyst stage in SCNT embryos. CONCLUSIONS: Cytokine supplementation increased efficiency of in vitro production of IVF and SCNT embryos and in vivo development of SCNT embryos to term. IMPLICATIONS: Cytokine supplementation is beneficial to embryo culture systems, which may shed light on requirements of early embryo development.
Differential expression and localisation of heat shock protein 70 (HSP70) and glutathione peroxidase 5 (GPX5) in the testis and epididymis of Sonid Bactrian camels.
Hasi G, Wu L, Sodnompil T … +8 more , Yi R, Wu R, Zhang R, Na H, Liu H, Ji M, Xie W, Nasenochir N
Reprod Fertil Dev · 2023 Jun · PMID 37290785 · Publisher ↗
CONTEXT: Heat shock protein 70 (HSP70) and glutathione peroxidase 5 (GPX5) are biomarkers of oxidative stress and stress in temperate, tropical environments, which are crucial for male reproduction. Their expression and...
CONTEXT: Heat shock protein 70 (HSP70) and glutathione peroxidase 5 (GPX5) are biomarkers of oxidative stress and stress in temperate, tropical environments, which are crucial for male reproduction. Their expression and distribution patterns in the testis and epididymis of Bactrian camels are still unknown. AIMS: This study aims to investigate the HSP70 and GPX5 expression and localisation in 3- and 6-year-old Bactrian camel testis and epididymis. METHODS: Reverse transcription quantitative polymerase chain reaction (qRT-PCR), Western blot and immunohistochemistry were used to detect HSP70 in the testis and epididymis (caput, corpus and cauda) and GPX5 in the epididymis at two developmental stages (3-year-old puberty group and 6-year-old adult group). KEY RESULTS: HSP70 was upregulated in the testis. Immunohistochemistry results indicated the HSP70 protein was mainly detected in spermatids and Leydig cells of testicular tissue. In the epididymis, HSP70 was located at the luminal spermatozoa, the epithelium lining the epididymal and the epididymal interstitium. GPX5 expression was significantly higher in the caput epididymis than in the corpus and cauda epididymis. GPX5 protein was observed in the epithelium lining the epididymal, interstitium and luminal spermatozoa in the epididymis by immunohistochemistry. CONCLUSIONS: Bactrian camel HSP70 and GPX5 exhibited spatiotemporal expression specificity. IMPLICATIONS: HSP70 and GPX5 may be essential for germ cell development and reproductive success after sexual maturation in Sonid Bactrian camels.
The melatonin system is expressed in the ovine uterus: effect of the day of the oestrous cycle and undernutrition.
Sosa C, Laurenzana E, de Brun V … +2 more , Meikle A, Abecia JA
Reprod Fertil Dev · 2023 Jul · PMID 37290449 · Publisher ↗
CONTEXT: Melatonin influences female reproduction, but expression of the melatonin system has not been characterised in the ovine uterus. AIMS: We aimed to determine whether synthesising enzymes (arylalkylamine N-acetylt...
CONTEXT: Melatonin influences female reproduction, but expression of the melatonin system has not been characterised in the ovine uterus. AIMS: We aimed to determine whether synthesising enzymes (arylalkylamine N-acetyltransferase (AANAT) and N-acetylserotonin-O-methyltransferase (ASMT)), melatonin receptors 1 and 2 (MT1 and MT2), and catabolising enzymes (myeloperoxidase (MPO) and indoleamine 2,3-dioxygenase 1 and 2 (IDO1 and 2)), are expressed in the ovine uterus, and if they are influenced by the oestrous cycle (Experiment 1) or by undernutrition (Experiment 2). METHODS: In Experiment 1, gene and protein expression was determined in sheep endometrium samples collected on days 0 (oestrus), 5, 10 and 14 of the oestrous cycle. In Experiment 2, we studied uterine samples from ewes fed either 1.5 or 0.5times their maintenance requirements. KEY RESULTS: We have demonstrated the expression of AANAT and ASMT in the endometrium of sheep. AANAT and ASMT transcripts, and AANAT protein were more elevated at day 10, then decreased to day 14. A similar pattern was observed for MT2 , IDO1 , and MPO mRNA, which suggests that the endometrial melatonin system might be influenced by ovarian steroid hormones. Undernutrition increased AANAT mRNA expression, but seemed to decrease its protein expression, and increased MT2 and IDO2 transcripts, whereas ASMT expression was unaffected. CONCLUSIONS: The melatonin system is expressed in the ovine uterus and is affected by oestrous cycle and undernutrition. IMPLICATIONS: The results help explain the adverse effects of undernutrition on reproduction in sheep, and the success of exogenous melatonin treatments in improving reproductive outcomes.
The effects of cycloastragenol on bovine embryo development, implantation potential and telomerase activity.
Khan AM, Idrees M, Perera CD … +5 more , Haider Z, Joo MD, Kang JS, Lee SH, Kong IK
Reprod Fertil Dev · 2023 Jun · PMID 37263290 · Publisher ↗
CONTEXT: Telomerase reverse transcriptase is a key factor responsible for structural and cellular alterations in aged oocytes and changes in the structure of the zona pellucida and mitochondria. Telomerase expression is...
CONTEXT: Telomerase reverse transcriptase is a key factor responsible for structural and cellular alterations in aged oocytes and changes in the structure of the zona pellucida and mitochondria. Telomerase expression is reduced in aged cumulus oocyte complexes, and its activation or enhanced expression would be beneficial for in vitro oocyte maturation and in vitro embryo development. AIMS: This study aimed to investigate telomerase activation by cycloastragenol and its effect on bovine oocyte in vitro maturation, fertilisation, and early embryo development. METHODS: We used qPCR, Western blot, immunofluorescence, reactive oxygen species (ROS) assay,TUNEL assay, JC-1 assay, and invasion assay to analyse the affect of cycloastragenol (CAG) on bovine oocyte maturation, embryo development, embryo quality and implantation potential. KEY RESULTS: Cycloastragenol treatment of oocytes in in vitro maturation (IVM) media significantly (P <0.05) improved oocyte IVM (90.87%), embryo cleavage (90.78%), blastocyst hatching (27.04%), and embryo implantation potential. Telomerase also interacts with mitochondria, and JC-1 staining results showed significantly (P <0.05) higher mitochondrial membrane potential (ΔΨ m) in the CAG-treated group. Furthermore, the inner cell mass (OCT4 and SOX2) and trophoblasts (CDX2) of the control and CAG groups were examined. Moreover, CAG treatment to primary cultured bovine cumulus cells substantially enhanced telomerase activity. CONCLUSIONS: Telomerase activation via cycloastragenol is beneficial for bovine oocyte IVM and for the production of high-quality bovine embryos. IMPLICATIONS: Cycloastragenol is a natural telomerase activator, and could be useful as a permanent component of oocyte maturation media.
Redox profile and mediators of the unfolded protein response (UPR) in the placenta of rats during pregnancy.
Dos Anjos Cordeiro JM, Santos LC, Santos BR … +7 more , Santos EO, Nascimento AEJ, Freitas GJC, Singulani JL, Santos DA, Lavor MSL, Silva JF
Reprod Fertil Dev · 2023 Jun · PMID 37257504 · Publisher ↗
CONTEXT: Proliferation, differentiation, migration and apoptosis of trophoblastic cells are influenced by hypoxia, as well as adequate modulation of oxidative stress and the unfolded protein response (UPR) pathway. AIMS:...
CONTEXT: Proliferation, differentiation, migration and apoptosis of trophoblastic cells are influenced by hypoxia, as well as adequate modulation of oxidative stress and the unfolded protein response (UPR) pathway. AIMS: We aimed to evaluate the expression profile of redox and UPR mediators in the placenta of rats throughout pregnancy. METHODS: Placental expression of hypoxia-inducible factor 1α (HIF1α), 8-Hydroxy-2'-deoxyguanosine (8-OHdG), superoxide dismutase 1 (SOD1), glutathione peroxidase (GPX), catalase (Cat), activating transcription factor 6 (ATF6), protein kinase RNA-like endoplasmic reticulum kinase (PERK), 78 kD glucose-regulated protein (GRP78) and C/EBP-homologous protein (CHOP), as well as reactive oxygen species (ROS) and peroxynitrite production, were evaluated in Wistar rats on the 10th, 12th, 14th, 16th and 18th day of pregnancy (DP). KEY RESULTS: Increased immunostaining of HIF1α was observed on the 16th and 18th DP, while 8-OHdG and ROS production were greater on the 14th DP. SOD1 and Cat had increased immunostaining on the 14th and 18th DP, while staining of GPX1/2, GRP78 and CHOP was greater on the 18th DP. With regard to gene expression, Hif1α and Sod1 showed increased mRNA expression on the 12th and 16th DP, while Gpx1 had increased expression on the 10th and 16th DP. Cat , Perk and Grp78 gene expression was greater on the 14th DP, unlike Atf6 , which showed greater expression on the 12th DP. In contrast, Chop maintained increased expression from the 12th to the 18th DP. CONCLUSIONS: The placental expression of redox and UPR mediators in rats is influenced by gestational age, with greater expression in periods of greater HIF1α and 8-OHdG expression and at the end of the pregnancy. IMPLICATIONS: This study provides data on the physiological modulation of redox and UPR mediators during placental development in rats.
Sphingosine-1-phosphate regulation of luteinising hormone-induced steroidogenesis and proliferation of bovine theca cells .
Medina-Moctezuma ZB, Hernández-Coronado CG, Marín-López L … +4 more , Guzmán A, González-Aretia D, Gutiérrez CG, Rosales-Torres AM
Reprod Fertil Dev · 2023 Jun · PMID 37225163 · Publisher ↗
CONTEXT: Sphingosine-1-phosphate (S1P) is synthesised by follicle granulosa cells under the influence of follicle-stimulating hormone and seems to be necessary for the biological effects of this gonadotrophin. AIMS: To d...
CONTEXT: Sphingosine-1-phosphate (S1P) is synthesised by follicle granulosa cells under the influence of follicle-stimulating hormone and seems to be necessary for the biological effects of this gonadotrophin. AIMS: To determine if luteinising hormone (LH) increases S1P production and if this sphingolipid, either induced by LH or added to culture media, regulates steroidogenesis and cell viability in bovine theca cells. METHODS: We used bovine theca cell cultures treated with: S1P (0, 0.1, 1 and 10μM; Experiment 1), LH (0, 0.02, 0.2 and 2ngmL-1 ; Experiment 2) and LH (0.02ngmL-1 ) plus a sphingosine kinase inhibitor (SKI-178; 0, 5 and 10μM; Experiment 3). KEY RESULTS: Treatment with S1P did not affect (P >0.05) theca cell viability or their ability to produce progesterone and testosterone. LH (0.02ngmL-1 ) increased (P <0.05) S1P production, and stimulated the expression of phosphorylated sphingosine kinase-1 (pSPHK1). However, the inhibition of SPHK1, by a specific SPHK1 inhibitor (SKI-178), reduced (P <0.05) cell viability and progesterone secretion. Additionally, the use of SKI-178 increased theca cell testosterone production (P<0.05). CONCLUSIONS: S1P added to culture media did not affect cell viability or steroid synthesis. However, LH stimulated the production of S1P, by increasing phosphorylation of SPHK1 in theca cells. This intracellular S1P was inhibitory on testosterone production but augmented progesterone and viable cell number. IMPLICATIONS: These results suggest a novel signalling pathway for LH in theca cells and underline the importance of S1P in the regulation of steroid synthesis.
: Betaine ameliorates high glucose-induced oxidative stress in granulosa cells.
Abnosi MH, Tabandeh MR, Mosavi-Aroo F
Reprod Fertil Dev · 2023 May · PMID 37224073 · Publisher ↗
CONTEXT: In diabetes, abnormalities of granulosa cells (GCs) and steroidogenesis are associated with hyperglycaemia-induced oxidative stress. Betaine has beneficial effect in experimental model of diabetes by reducing ox...
CONTEXT: In diabetes, abnormalities of granulosa cells (GCs) and steroidogenesis are associated with hyperglycaemia-induced oxidative stress. Betaine has beneficial effect in experimental model of diabetes by reducing oxidative stress, inflammation, and apoptosis. AIMS: In this study we investigate the effects of betaine to prevent oxidative stress in GCs induced by high glucose and improve steroidogenesis. METHODS: Primary GCs, isolated from ovarian follicles of C57BL/6 mice were cultured in 5mM (control) and 30mM (hyperglycaemia) of glucose and in presence of 5mM of betaine for 24h. Then antioxidant enzymes, malondialdehyde, oestradiol and progesterone were measured. In addition, the expression of Nrf2 and NF-κB , antioxidant enzymes (Sod1 , Gpx and Cat ) were analysed by qRT-PCR assay. KEY RESULTS: We observed significant (P NF-κB and down-regulation of Nrf2 due to high concentration of glucose. Also significant (P Cat , Sod1 and GPx ) and activity reduction of these enzymes as well as significant (P NF-κB and up-regulating the expression of Nrf2 , Cat , Sod1 and GPx . It was also shown that betaine in the presence of FSH significantly (P Conclusion: Betaine compensated the antioxidant stress in mouse GCs under hyperglycaemic condition via regulation of Nrf2/NF-κB at transcription level. IMPLICATIONS: As betaine is a natural product and no side effect has been reported to today, we suggest more research needs to be carried out especially on patients whom suffer from diabetes to find the probability of using betaine as a therapeutic agent.
The intertwining roles of caveolin, oxytocin receptor, and the associated signalling pathways in prostate cancer progression.
Gould ML
Reprod Fertil Dev · 2023 Jun · PMID 37217187 · Publisher ↗
Caveolae are invaginations in the plasma membrane of most cell types and are present in the cells of normal prostate tissue. Caveolins are a family of highly conserved integral membrane proteins that oligomerise to form...
Caveolae are invaginations in the plasma membrane of most cell types and are present in the cells of normal prostate tissue. Caveolins are a family of highly conserved integral membrane proteins that oligomerise to form caveolae and interact with signalling molecules by providing a scaffold that sequesters signal transduction receptors in close proximity to each other. Signal transduction G proteins and G-protein-coupled receptors (GPCR), including oxytocin receptor (OTR), are localised within caveolae. Only one OTR has been identified, and yet, this single receptor both inhibits and stimulates cell proliferation. As caveolae sequester lipid-modified signalling molecules, these differing effects may be due to a change in location. The cavin1 necessary for caveolae formation is lost in prostate cancer progression. With the loss of caveolae, the OTR moves out onto the cell membrane influencing the proliferation and survival of prostate cancer cells. Caveolin-1 (cav-1) is reportedly overexpressed in prostate cancer cells and is associated with disease progression. This review focuses on the position of OTRs within caveolae, and their movement out onto the cell membrane. It explores whether movement of the OTR is related to changes in the activation of the associated cell signalling pathways that may increase cell proliferation and analyse whether caveolin and particularly cavin1 might be a target for future therapeutic stratagies.
Impact of regulatory T cell therapy on immune cell composition and fetal survival rate in abortion prone mice.
Idali F, Golshahi H, Katouzian L … +3 more , Notash Haghighat F, Rezaii-Nia S, Jeddi-Tehrani M
Reprod Fertil Dev · 2023 Jun · PMID 37211528 · Publisher ↗
CONTEXT: Implantation of fertilised eggs and survival of a semi-allogenic embryo rely on the interactions between the cells and molecules preparing the uterus. We investigated the effect of regulatory T cell (Treg) thera...
CONTEXT: Implantation of fertilised eggs and survival of a semi-allogenic embryo rely on the interactions between the cells and molecules preparing the uterus. We investigated the effect of regulatory T cell (Treg) therapy on the mechanism of local immune tolerance of mice prone to spontaneous abortion. METHODS: Naive T cells were stimulated in vitro with 17β-oestradiol (E2), progesterone (P4) and TGF-β1 for 96h to generate induced Tregs (iTreg). The iTregs were injected into DBA/2-mated pregnant CBA/J female mice (abortion prone model). On day 14 of pregnancy, mice were killed and decidual and placental tissues were collected for cellular composition analysis. RESULTS: Abortion prone mice (PBS treated) showed significantly lower survival rates (P <0.0001), increased CD3+ CD8+ (P <0.05), lower IDO+ (P <0.05) and increased natural killer cells (uNK) cell numbers (P <0.001) in the uterus, as well increased NK cells in the placenta (P <0.05) than in normal pregnant mice (CBA/J×BALB/c). Adoptive transfer of iTregs increased fetal survival in abortion-prone mice (P <0.01) and histopathological evaluation revealed a significantly decreased number of uNK cells in the uterus of TGF-β1-, E2- and P4-iTregs (P<0.05, P<0.0001 and P<0.05, respectively) than in the PBS treated group. In the placenta, we found significantly lower numbers of uNK cells from TGF-β1-, E2- and P4-iTregs than in the PBS treated group (P <0.05, P <0.05 and P <0.01, respectively). CONCLUSIONS: We propose that modulation of uterine NK cell activity through immunotherapy using Treg cells should be given more attention as an immunological strategy in the treatment of recurrent miscarriage.
The impact of leptin on sperm.
Almabhouh FA, Singh HJ
Reprod Fertil Dev · 2023 May · PMID 37196661 · Publisher ↗
Despite its important role in numerous physiological functions, including regulation of appetite and body weight, immune function and normal sexual maturation, raised leptin levels could result in significant damaging ef...
Despite its important role in numerous physiological functions, including regulation of appetite and body weight, immune function and normal sexual maturation, raised leptin levels could result in significant damaging effects on sperm. The adverse effects of leptin on the male reproductive system result from its direct actions on the reproductive organs and cells instead of the hypothalamus-pituitary-gonadal axis. Binding of leptin to the receptors in the seminiferous tubular cells of the testes increases free radical production and decreases the gene expression and activity of endogenous enzymatic antioxidants. These effects are mediated via the PI3K pathway. The resultant oxidative stress causes significant damage to the seminiferous tubular cells, germ cells and sperm DNA leading to apoptosis, increased sperm DNA fragmentation, decreased sperm count, increased fraction of sperm with abnormal morphology, and decreased seminiferous tubular height and diameter. This review summarises the evidence in the literature on the adverse effects of leptin on sperm, which could underlie the often-reported sperm abnormalities in obese hyperleptinaemic infertile males. Although leptin is necessary for normal reproductive function, its raised levels could be pathologic. There is, therefore, a need to identify the cut-off level in the serum and seminal fluid above which leptin becomes pathological for better management of leptin associated adverse effects on male reproductive function.
Betulonic acid regulates oviduct epithelial cell inflammation through the TLR4, MAPK, and JAK/STAT signalling pathways.
Shao L, Yan Y, Wang N … +5 more , Tan Q, Huang Y, Lei L, Yang D, Liu L
Reprod Fertil Dev · 2023 May · PMID 37142241 · Publisher ↗
CONTEXT: Infertility is a common disease among women of childbearing age and seriously endangers the reproductive health of human beings. AIMS: We aimed to study the active effect and mechanism of betulonic acid (BTA) on...
CONTEXT: Infertility is a common disease among women of childbearing age and seriously endangers the reproductive health of human beings. AIMS: We aimed to study the active effect and mechanism of betulonic acid (BTA) on tubal inflammatory infertility. METHODS: An inflammatory model was established in isolated rat oviduct epithelial cells. Immunofluorescence of cytokeratin 18 was performed in cells. The therapeutic effect of BTA on cells was observed. Subsequently, we added JAK/STAT inhibitor AG490 and MAPK inhibitor U0126 and measured the levels of inflammatory factors via enzyme-linked immunosorbent assay and qRT-PCR. CCK-8 assay was applied to test cell proliferation, whereas flow cytometry was used to measure apoptosis. The levels of TLR4, IκBα, JAK1, JAK2, JAK3, Tyk2, STAT3, p38, ERK and the phosphorylation of p65 were determined by Western blotting. KEY RESULTS: Betulonic acid inhibited the activation of TLR4 and NF-κB signalling pathways, and significantly downregulated IL-1β, IL-6, and TNF-α, with high doses being the most effective. Furthermore, high-dose BTA promoted the proliferation of oviduct epithelial cells and inhibited apoptosis. In addition, BTA inhibited the activation of JAK/STAT signalling pathway to perform effectively in oviduct epithelial cells inflammation. The addition of AG490 led to the inhibition of the JAK/STAT signalling pathway. BTA also inhibited the activation of MAPK signalling pathway in oviduct epithelial cells inflammation. Under U0126 treatment, the inhibition of proteins in MAPK pathway by BTA was weakened. CONCLUSIONS: Therefore, BTA inhibited the TLR, JAK/STAT and MAPK signalling pathways. IMPLICATIONS: Our study provided a new therapeutic strategy for infertility caused by oviduct inflammation.
Sulfasalazine exposure during pregnancy and lactation: reproductive outcomes in male rat offspring.
Forcato S, Aquino ABO, Borges LI … +7 more , Thomé MLFL, Bilibio JO, Lens HHM, Erthal RP, Guarnier FA, Fernandes GSA, Gerardin DCC
Reprod Fertil Dev · 2023 May · PMID 37080254 · Publisher ↗
CONTEXT: Sulfasalazine (SAS) is a drug prescribed for pregnant and breastfeeding women with chronic inflammatory bowel diseases. SAS treatment induces transitory infertility in both adult men and male rats. Although SAS...
CONTEXT: Sulfasalazine (SAS) is a drug prescribed for pregnant and breastfeeding women with chronic inflammatory bowel diseases. SAS treatment induces transitory infertility in both adult men and male rats. Although SAS crosses the placenta and passes into maternal milk, the consequences of maternal SAS exposure on the reproductive development of male offspring needs further study. AIMS: The current study evaluated whether maternal SAS exposure interferes with the reproductive development of male rat offspring in the neonatal, infant, pubertal and adulthood periods. METHODS: Pregnant Wistar rats (n =10/group) received 300mg/kg/day of SAS dissolved in carboxymethyl cellulose (CMC), by gavage, from gestational day 0 to lactation day 21, and 3mg/kg/day of folic acid during gestation. The control group received CMC. KEY RESULTS: During puberty, maternal SAS exposure increased the total length of seminiferous tubules, and round cells were observed in the lumen of caput and cauda epididymis. Moreover, SAS induced oxidative stress-related alterations in the testes of infant and adolescent rats. CONCLUSIONS: Although maternal SAS treatment caused reproductive alterations in infant and adolescent male rats, in adulthood, there were no impairments in sperm parameters that could compromise fertility. IMPLICATIONS: This study investigated the consequences of maternal exposure to SAS on the reproductive development of male rat offspring from birth to adulthood, employing a human-relevant dose. Thus, this study provides information for better understanding of SAS treatment during critical periods of development.
Melatonin improves the ability of spermatozoa to bind with oocytes in the mouse.
Liu Y, Zhang Y, Wang Z … +5 more , Teng Z, Zhu P, Xie M, Liu F, Liu X
Reprod Fertil Dev · 2023 Apr · PMID 37068786 · Publisher ↗
CONTEXT AND AIMS: Melatonin is a powerful antioxidant regulating various biological functions, including alleviating male reproductive damage under pathological conditions. Here, we aim to analyse the effect of melatonin...
CONTEXT AND AIMS: Melatonin is a powerful antioxidant regulating various biological functions, including alleviating male reproductive damage under pathological conditions. Here, we aim to analyse the effect of melatonin on normal male reproduction in mice. METHODS: Male mice received an intraperitoneal injection of melatonin (10mg/kg body weight) for 35 consecutive days. The testis and epididymis morphology, and epididymal sperm parameters were examined. PCNA, HSPA2, SYCP3, ZO-1 and CYP11A1 expressions in epididymis or testis were detected by immunohistochemistry or Western blotting. Male fertility was determined by in vivo and in vitro fertilisation (IVF) experiments. The differentially expressed sperm proteins were identified by proteomics. KEY RESULTS: No visible structural changes and oxidative damage in the testis and epididymis, and no significant side effects on testis weight, testosterone levels, sperm motility, and sperm morphology were observed in the melatonin-treatment group compared with the control group. Spermatogenesis-related molecules of PCNA, SYCP3, ZO-1, and CYP11A1 showed no significant differences in melatonin-treated testis. However, PCNA and HSPA2 increased their expressions in the epididymal initial segments in the melatonin-treatment group. Normal sperm fertilisation, two-cell and blastocyst development were observed in the melatonin-treated group, but melatonin significantly enhanced the sperm binding ability characterised as more sperm binding to one oocyte (control 7.2±1.3 versus melatonin 11.8±1.5). Sperm proteomics demonstrated that melatonin treatment enhanced the biological process of cell adhesion in sperm. CONCLUSIONS AND IMPLICATIONS: This study suggests that melatonin can promote sperm maturation and sperm function, providing important information for further research on the physiological function and protective effect of melatonin in male reproduction.
Pentoxifylline promotes spermatogenesis via upregulation of the Nrf2-ARE signalling pathway in a mouse model of germ-cell apoptosis induced by testicular torsion-detorsion.
Akanji OD, Hassanzadeh G, Malekzadeh M … +4 more , Khanmohammadi N, Khanezad M, Sadeghiani G, Rastegar T
Reprod Fertil Dev · 2023 Apr · PMID 37062868 · Publisher ↗
CONTEXT: Testicular torsion-detorsion results in loss of germ cells and infertility. Pentoxifylline has been shown to prevent tissue damage. AIMS: To determine the effect of pentoxifylline on germ cell survival in torsio...
CONTEXT: Testicular torsion-detorsion results in loss of germ cells and infertility. Pentoxifylline has been shown to prevent tissue damage. AIMS: To determine the effect of pentoxifylline on germ cell survival in torsion-detorsion induced apoptosis Methods: Twenty male mice were divided into four groups of five animals each: Control, T1 (Torsion-detorsion+single dose 100mg/kg Pentoxifylline/IP), T2 (Torsion-detorsion+daily 20mg/kg pentoxifylline/IP for 2weeks, and T/D (Torsion-detorsion only). 35thday after torsion-detorsion, the left testes of all the animals were harvested for histological and biochemical analysis. KEY RESULTS: Histomorpholoical analysis showed significant increase (P <0.05) in seminiferous tubule diameter, Johnsen's score and germ cells of Control and T1 compared to T2 and T/D, with no significant difference (P >0.05) in testis weight, sertoli, leydig and myoid cells. Tunnel assay showed significant increase (P <0.05) in apoptotic cells of T/D and T2 animals compared to Control and T1. RT-PCR analysis showed significant high (P <0.01) mRNA expression of Bax gene in T/D compared to T1 and T2 and significant increase (P <0.05) of Bcl2 in Control, T1, T2 compared to T/D. Nrf2-ARE transcripts revealed significant increase (P <0.05) in Control and T1 compared to T2 and T/D. Western blot showed significantly increased (P <0.05) caspase-3 in T/D compared to Control, T1 and T2. CONCLUSION: Pentoxifylline promotes spermatogenesis and suppressed apoptosis induced by testicular torsion-detorsion. IMPLICATION: Pentoxifylline could serve as adjunct therapy to surgery in the treatment of torsion-detorsion induced germ cell apoptosis.
Platelet-rich plasma and ovarian quiescence: a bovine model for regeneration of the ovary.
Lange-Consiglio A, Gaspari G, Riccaboni P … +4 more , Canesi S, Bosi G, Vigo D, Cremonesi F
Reprod Fertil Dev · 2023 Apr · PMID 37044384 · Publisher ↗
CONTEXT: Ovarian quiescence can be due to hormonal deficiency usually caused by apoptosis of granulosa cells responsible for oestrogen synthesis. AIM: This study evaluated the regenerative effect of platelet rich plasma...
CONTEXT: Ovarian quiescence can be due to hormonal deficiency usually caused by apoptosis of granulosa cells responsible for oestrogen synthesis. AIM: This study evaluated the regenerative effect of platelet rich plasma (PRP) on bovine in vitro models to understand its effect on granulosa cells. METHODS: Quiescent and healthy ovarian sections were cultured in the presence/absence of PRP for 72h and, at different times (0, 24, 48 and 72h), hematoxylin-eosin and immunohistochemical detection of Ki-67 were performed. Additionally, granulosa cells collected from healthy bovine ovaries were stressed with 100ng/mL of lipopolysaccharide (LPS) in presence/absence of PRP and evaluated at 0, 4, 8 and 24h for apoptosis by acridine orange and propidium iodide staining. Enzyme-linked immunosorbent assay tests were performed to evaluate oestrogen (E2) and anti-Müllerian hormone (AMH) concentrations on cultures of ovarian slices and granulosa cells. KEY RESULTS: In slides of quiescent ovaries treated with PRP, a marked and widespread positivity to Ki-67 was expressed by 40-60% of the follicular wall cells at 48h of culture. Levels of E2 and AMH were significantly higher compared to untreated quiescent samples reaching the levels of healthy control samples. PRP counteracted the LPS effect and apoptosis (at 24h, there were 93.44±3.51% live cells with LPS+PRP compared to 37±1.32% with LPS) and significantly increased concentrations of E2 and AMH. CONCLUSIONS: PRP can stimulate granulosa cell proliferation and counteract inflammatory processes in vitro . IMPLICATIONS: This treatment could improve the reproductive ability of quiescent females.
Oviductal sperm storage in the Chinese pond turtle, , depends on androgen-based promotion of the BCL 2 anti-apoptotic pathway.
Chen W, Wang Y, Gong M … +5 more , Gao H, Zhou H, Bu X, Xia X, Nie L
Reprod Fertil Dev · 2023 Mar · PMID 36958022 · Publisher ↗
CONTEXT: Sperm storage is a complex and highly coordinated process that is regulated by a variety of factors. The BCL 2 protein family plays a key role in regulating apoptosis, and determines sperm survival. AIMS: The ob...
CONTEXT: Sperm storage is a complex and highly coordinated process that is regulated by a variety of factors. The BCL 2 protein family plays a key role in regulating apoptosis, and determines sperm survival. AIMS: The objective of this study was to explore the correlation between sperm storage and the BCL 2 protein family in the oviduct of Mauremys reevesii . METHODS: Hematoxylin-eosin (HE) staining, immunohistochemistry (IHC) and real-time quantitative polymerase chain reaction (RT-qPCR) techniques were used to investigate three parts of the reproductive tract (isthmus, uterus and vagina) of mated and unmated female M. reevesii . KEY RESULTS: Hematoxylin-eosin staining revealed many sperm stored in the oviduct. IHC showed positive immunostaining for the BCL 2 and BAX proteins in epithelial ciliated and glandular cells. RT-qPCR indicated that the mRNA expressions of anti-apoptotic genes (BCL 2 , MCL 1 , BCL- W , BCL-XL ) and the androgen receptor (AR) were significantly higher in mated turtles than unmated turtles. However, the expression of pro-apoptotic genes (BAX , BAD , BID and CASPASE 3 ) showed the opposite relationship. CONCLUSIONS: These results suggest that sperm entering the oviduct can promote the synthesis of anti-apoptotic genes to protect themselves from various degradation factors. IMPLICATIONS: These findings will help researchers understand the mechanisms of sperm storage.
Betaine ameliorates high glucose-induced oxidative stress in granulosa cells.
Abnosi MH, Tabandeh MR, Mosavi-Aroo F
Reprod Fertil Dev · 2023 Mar · PMID 36940486 · Publisher ↗
CONTEXT: In diabetes, abnormalities of granulosa cells (GCs) and steroidogenesis are associated with hyperglycaemia-induced oxidative stress. Betaine has beneficial effect in experimental model of diabetes by reducing ox...
CONTEXT: In diabetes, abnormalities of granulosa cells (GCs) and steroidogenesis are associated with hyperglycaemia-induced oxidative stress. Betaine has beneficial effect in experimental model of diabetes by reducing oxidative stress, inflammation, and apoptosis. AIMS: In this study we investigate the effects of betaine to prevent oxidative stress in GCs induced by high glucose and improve steroidogenesis. METHODS: Primary GCs, isolated from ovarian follicles of C57BL/6 mice were cultured in 5mM (control) and 30mM (hyperglycaemia) of glucose and in presence of 5mM of betaine for 24h. Then antioxidant enzymes, malondialdehyde, oestradiol and progesterone were measured. In addition, the expression of Nrf2 and NF-κB , antioxidant enzymes (Sod1 , Gpx and Cat ) were analysed by qRT-PCR assay. KEY RESULTS: We observed significant (P <0.001) up-regulation of NF-κB and down-regulation of Nrf2 due to high concentration of glucose. Also significant (P <0.001) down-regulation of related antioxidant genes (Cat , Sod1 and GPx ) and activity reduction of these enzymes as well as significant (P <0.001) elevation of malondialdehyde was observed. In addition, betaine treatment compensated the drastic effect of high glucose induced oxidative stress via down-regulating the expression of NF-κB and up-regulating the expression of Nrf2 , Cat , Sod1 and GPx . It was also shown that betaine in the presence of FSH significantly (P <0.001) restored the oestradiol and progesterone level. CONCLUSION: Betaine compensated the antioxidant stress in mouse GCs under hyperglycaemic condition via regulation of Nrf2/NF-κB at transcription level. IMPLICATIONS: As betaine is a natural product and no side effect has been reported to today, we suggest more research needs to be carried out especially on patients whom suffer from diabetes to find the probability of using betaine as a therapeutic agent.
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