Reproduction最新文献

In brief: NAD+ levels were reduced in streptozotocin (STZ)-induced diabetic mice, but nicotinamide riboside (NR) supplementation improved these levels in diabetic ovaries and oocytes, enhancing oocyte quality and early embryo development by improving mitochondrial function and lowering reactive oxygen species (ROS) levels.

Abstract: Diabetes mellitus is strongly correlated with a decline in oocyte quality; however, noninvasive and effective methods to improve this issue have yet to be fully development. Here, we demonstrate that in vivo supplementation with NR 400 mg/kg/day for 14 days effectively enhances the quality of oocytes from diabetic mice induced by streptozocin 190 mg/kg by restoring nicotinamide adenine dinucleotide (NAD+) levels. NR supplementation not only improved superovulation function of diabetic mice but also improved their oocyte quality and embryonic development potential after fertilization by maintaining normal spindle structure and alleviating mitochondrial dysfunction. In addition, NR supplementation reduced ROS levels in oocytes from diabetic mice. Overall, our findings suggest that dietary NR supplementation is a viable strategy to protect oocytes from diabetes-related deterioration, thereby enhancing reproductive outcomes in maternal diabetes and improving the efficacy of assisted reproductive technology.

In brief: Intrauterine inflammation disrupts tryptophan metabolism in both the placenta and the fetal brain, leading to a shift toward neurotoxic metabolites. These findings highlight the critical role of placental function in neurodevelopment and suggest that inflammation-induced metabolic changes may contribute to neurodevelopmental disorders.

Abstract: The placenta plays a crucial role beyond nutrient transfer, acting as a dynamic endocrine organ that significantly influences maternal physiology and fetal development. It responds rapidly to even slight changes in the in utero environment to promote fetal survival. Disruptions in placental function are increasingly recognized as key contributors to the origins of neurodevelopmental disorders. In this study, we employed advanced technology to induce intrauterine inflammation through ultrasound-guided administration of LPS into gestational sacs. We then evaluated its effects on the gene expression of enzymes involved in TRP metabolism and conducted a comprehensive LC/MS analysis of the metabolome in the placenta and fetal brain of Wistar rats. Our results show that intraamniotic injection of LPS induces a robust inflammatory response leading to significant alterations in TRP metabolism, including downregulation of tryptophan hydroxylase (TPH) in the placenta, resulting in a decrease in serotonin (5-HT) levels. Similarly, in the fetal brain, exposure to LPS led to reduced Tph expression and increased monoamine oxidase expression, suggesting a decrease in 5-HT synthesis and an increase in its degradation. Furthermore, an upregulation of the kynurenine pathway was observed in both the placenta and fetal brain. Moreover, we detected a shift toward neurotoxicity, evidenced by an imbalance between neuroprotective and neurotoxic metabolites, including decreased levels of kynurenic acid and upregulation of kynurenine monooxygenase in the fetal brain. In conclusion, our findings reveal significant alterations in TRP metabolism following intrauterine inflammation, potentially contributing to neurodevelopmental disorders.

In brief: Numerous studies have examined the impact of 2.45 GHz Wi-Fi exposure on the testes, highlighting concerns about its potential effects on male fertility. This study extends the investigation beyond the testes to include the epididymis, seminal vesicle and coagulating gland, providing a more comprehensive understanding of how 2.45 GHz Wi-Fi influences the male reproductive system.

Abstract: Numerous studies have documented the effect of 2.45 GHz Wi-Fi exposure on the testes and sperm quality. Nevertheless, detailed histological alterations of other male reproductive organs are underexplored. Therefore, this study aimed to evaluate detailed histological alterations of the testes, epididymis, seminal vesicle, coagulating organ and sperm parameters following 2.45 GHz Wi-Fi exposure. Eighteen adult male Sprague Dawley rats (n = 18) were equally divided into three groups (n = 6): control, 4 h and 24 h groups. The groups were exposed to an active router daily for 4 or 24 h, respectively. The control group was sham-exposed using an inactive router. The exposure lasted for 8 weeks at a 20 cm distance, with a power density of 0.141 W/m2 and a specific absorption rate of 0.41 W/Kg. Histological findings revealed vacuolation in the testes and the corpus epididymis of the 4 and 24 h groups. The seminal vesicle in both exposed groups exhibited multifocal atypical hyperplasia. Besides, the seminiferous tubule diameter decreased gradually in both exposed groups, with a substantial decrease in the 24 h group. The spermatogenesis index in 4 and 24 h groups also reduced significantly. The latter result was reflected in the sperm concentration, where both groups showed a significant reduction compared to the control group. Sperm motility also decreased significantly in the 4 h groups. Interestingly, there was a substantial increase in sperm viability in the 24 h group. These findings indicate that 2.45 GHz Wi-Fi exposure causes changes in the histology and histomorphometry measurement and impairs important sperm parameters. This highlights the consequences following Wi-Fi exposure on male reproductive health.

In brief: Early pregnancy loss (EPL) is a common pregnancy problem lacking preventive measures. This study shows that DMOG-preconditioned hUC-MSCs can reduce early embryo loss.

Abstract: EPL, a common pregnancy complication, yet has few effective preventive measures currently. To investigate whether dimethyloxaloylglycine (DMOG)-preconditioned human umbilical cord mesenchymal stem cells (hUC-MSCs) can prevent EPL, we initially evaluated the effect of DMOG on hUC-MSCs in vitro. Subsequently, the DMOG-preconditioned hUC-MSCs were transplanted into the lipopolysaccharide (LPS)-induced murine abortion model for intervention, following which we conducted phenotypic analysis. It was found that DMOG treatment enhanced the mRNA expression of HIF1A, H19 and GLUT1 in hUC-MSCs and augmented their migration capability (P < 0.01). Co-culture experiments showed that DMOG-treated hUC-MSCs notably reduced the mRNA levels of IL6, IL1B and TNFA in LPS-induced HTR-8/SVneo cells (P < 0.01). Moreover, DMOG-preconditioned hUC-MSCs remarkably decreased the fetal resorption rate and increased the embryo weight in LPS-induced abortive mice (P < 0.01). Histological analysis indicated that DMOG-preconditioned hUC-MSCs more effectively promoted their homing and inhibited LPS-induced fibrosis at the maternal-fetal interface. Apart from suppressing inflammatory factors in the serum of pregnant mice, DMOG-preconditioned hUC-MSCs can downregulate the mRNA levels of Il2, Il1b, Tnfa, Il5 and Il9 (P < 0.01), which are pro-inflammatory cytokines secreted by M1 macrophages; and simultaneously upregulate the expression of Cd206 and Pparg (P < 0.01), which serve as the cell surface and nuclear receptors of M2 macrophages in the embryos. Immunofluorescence further verified that the transplantation of DMOG-preconditioned hUC-MSCs could increase the expression of CD206 in embryos. Therefore, DMOG-preconditioned hUC-MSCs might prevent EPL by promoting the transformation of M1 into M2 macrophages.

In brief: Oocytes with subtle differences in chromatin configuration and nuclear lamina characteristics, detectable by a refined germinal vesicle (GV) classification system here described, respond differently to meiotic maturation systems leading to different in vitro maturation (IVM) outcomes.

Abstract: The nuclear, cytoplasmic and molecular maturation of the mammalian oocyte is a finely orchestrated sequence of events that relies on proper cumulus-oocyte communication. Bovine oocytes enter the IVM systems at the GV stage exhibiting four different chromatin configurations (GV0-GV3). Herein, we associate the oocyte chromatin and nuclear lamina configurations to propose a refined GV classification (GV0, GV1.1-GV1.3, GV2.1-GV2.3 and GV3.1-GV3.3). This refined GV classification system was correlated with oocyte meiosis resumption and transzonal projections (TZPs) density of cumulus-oocyte complexes (COCs) submitted to three IVM systems (control IVM and a modified IVM preceded or not by a pre-IVM step). Pre-IVM resulted in lower polar body extrusion rates at 19 h IVM, albeit ∼24% of the oocytes extruded their first polar body at 9 h IVM. Pre-IVM sustained 80% of oocytes meiotically arrested but altered GV distribution, reducing GV2 and increasing GV1.3 and GV3.3 categories. Pre-IVM reduced TZP densities predominantly in pre-matured GV3 and GVBD COCs. At 9 h of IVM, both groups matured in modified IVM showed lower TZP densities compared to immature and IVM control. Gene expression supports the TZP density differences, with ERK2 and PRKACA upregulation in pre-matured cumulus and in modified IVM groups at 9 h of IVM. GDF9 and BMP15 levels were similar between treated and control groups at all time points. Our findings indicate that despite the IVM system, the initial oocyte GV stage influences pre-IVM and IVM outcomes. The refined GV classification system is a useful tool to oocyte biologists.

In brief: The transition from histones to protamines during spermiogenesis is critical for male genome integrity and influences fertilisation and early embryogenesis. This study reveals that specific 5' UTR single nucleotide polymorphisms (SNPs) and promoter methylation of the H2BC1 gene may regulate TSH2B expression in sperm, contributing new insights into the regulatory mechanisms of testis-specific genes and their implications for male fertility.

Abstract: The transition from histones to protamines during spermiogenesis plays a crucial role in shaping the male epigenome, and any changes in this process can impact fertilisation potential and the ability of sperm to support early embryogenesis. In our previous research, we observed reduced levels of TSH2B in the sperm of infertile men with oligozoospermia and oligoasthenozoospermia. However, the regulatory mechanisms of the H2BC1 gene, which encodes TSH2B, in the testes are not yet understood. In this study, we investigated whether H2BC1 expression is influenced by SNPs in the 5' untranslated region (5' UTR) and promoter methylation. Luciferase assays were performed to assess the impact of 5' UTR variants in vitro and pyrosequencing was done to evaluate promoter methylation of the H2BC1 gene in the sperm of fertile and infertile men. Our findings suggest that the 5' UTR variants rs4711096 (c.-83A>G) and rs4712959 (c.-80C>T) positively regulate H2BC1 expression. Methylation analysis indicates hypermethylation of CpG sites, particularly at CpGs 2, 3 and 9 in H2BC1, can influence H2BC1 expression. This study offers new insights into the regulation of testis-specific genes.

In brief: This review article summarizes the effects of pre- or peri-conceptual exposure to cannabinoids on female and male reproductive function, along with pregnancy outcomes from 2014 to 2024. In particular, it addresses the gaps in knowledge regarding the specific contributions of the major constituents of cannabis, THC and CBD, on reproduction.

Abstract: With increased use of cannabis worldwide, especially in our young adult population, there is a great impetus to understand the impact of cannabis and its constituents (i.e. THC and CBD) on pregnancy, fetal outcomes and male and female reproductive function. This review assessed the current evidence (2014-2024) regarding the effects of cannabinoids on reproductive function (male, female and pregnancy) in animal and human studies. In particular, pre- or periconceptual exposure to cannabinoids were assessed to determine their effects across the lifespan along with transgenerational effects. From the outcomes of this review, we conclude there is a greater need for future preclinical and clinical studies to assess how various routes of cannabinoid exposure along with differing mixtures of cannabinoid constituents may interact to impede reproductive health. Collectively, the outcomes of these studies are important to clinicians and regulatory agencies in the context of functional evidence to support policy and decision-making regarding the safety of cannabis use.

We synthesize current evidence that granulosa cells possess unique innate immune signaling capabilities. We suggest the novel concept that this serves as a quality control surveillance mechanism by integrating signals from the oocyte and ovarian microenvironment to prevent poor-quality follicles from producing gametes that contribute to the next generation.

In brief: The role of inflammation in the regulation of pregnancy remains poorly understood in dogs. Findings from this study propose the involvement of IL1β signaling during early embryo-maternal interactions in the dog, while in vitro effects suggest it may disrupt decidual cell function in the canine mature placenta.

Abstract: Although implantation and parturition are associated with pro-inflammatory signals, inflammatory responses in the mature placenta frequently lead to pregnancy loss. Indeed, uterine inflammatory/infectious diseases are major causes of infertility and pregnancy loss in dogs. The pro-inflammatory interleukin (IL)-1β is increased during canine placentation and downregulated in mature placentae during healthy pregnancies but is enriched in the placenta during infectious events. Furthermore, canine pregnancy success is linked with decidual cells, the only placental cells expressing the nuclear progesterone receptor. This study assessed utero-placental abundance of IL1β receptor 1 (IL1R1) throughout canine pregnancy and possible modulatory effects of IL1β on decidualization. The mRNA levels of IL1R1 were increased in mature mid-gestation placentae and at term (P < 0.05). Immunohistochemistry co-localized IL1β and IL1R1 in the trophoblast during early placentation, implicating IL1β-signaling in early embryo-maternal communication. In the mature placenta, IL1R1 was localized, i.a. in decidual cells. In vitro, IL1β had low modulatory effects on PGE2- and/or P4-stimulated dog uterine stromal (DUS) cells, implying a relatively weak impact of this interleukin in the decidualization process. However, in DUS cells decidualized with cAMP, IL1β decreased transcriptional amounts of selected decidualization markers IGF1, PTGS2 and PTGES, as well as ECM1 and TIMP2 (P < 0.001). Transcriptional and protein availabilities of CX43, a gap junction component, were also decreased by IL1β (P < 0.001). These findings support a dual role for IL1β in canine pregnancy: involvement in early embryo-maternal communication during its establishment and disturbing placental homeostasis by disrupting decidual cell function in fully developed placenta.

In brief: Severely deficient levels of vitamin D (VD) affect ovarian cellular function reducing production of androstenedione and oestradiol and insulin receptor expression; although mildly deficient levels have no effect.

Abstract: Numerous studies have investigated the link between VD deficiency and reproductive outcomes with contradictory results. VD regulates steroidogenic enzymes crucial for human granulosa and cumulus cell function. This study investigated whether deficient levels of 1,25-(OH)2-D3 altered ovarian cell function, and if the ovary could obtain bioactive 1,25-(OH)2-D3 via local enzymatic expression of CYP27B1 to counteract systemic deficiency. A variety of cells and tissues were used for the in vitro experiments. We have shown for the first time an increase in VDR expression in theca of large compared to small follicles, which along with the ability of 1,25-(OH)2-D3 to decrease anti-Müllerian hormone expression, supports a role for 1,25-(OH)2-D3 in theca and granulosa cell function. Conversely, very low levels of 1,25-(OH)2-D3 equivalent to hypovitaminosis inhibited thecal production of androstenedione and cAMP-driven oestradiol production. Human thecal and un-luteinised GC are incredibly hard to obtain for research purposes, highlighting the uniqueness of our dataset. We also demonstrated that deficient levels of 1,25-(OH)2-D3 downregulated insulin receptor expression, potentially reducing insulin sensitivity. We have shown that the ovary expresses CYP27B1, potentially allowing it to make local bioactive 1,25-(OH)2-D3, which along with the upregulation in VDR expression in ovarian cellular compartments could be protective locally in counteracting systemic VD deficiency. To conclude, a severely deficient VD environment (<2 nM or <1 ng/mL) could contribute to impaired ovarian cell function, and hence, potentially affect folliculogenesis/ovulation, but levels associated with mild deficiency may have less impact, apart from in the presence of hyperinsulinaemia and insulin resistance.