Transcriptome profile of goat folliculogenesis reveals the interaction of oocyte and granulosa cell in correlation with different fertility population.

To understand the molecular and genetic mechanisms related to the litter size in one species of two different populations (high litter size and low litter size), we performed RNA-seq for the oocytes and granulosa cells (GCs) at different developmental stages of follicle, and identified the interaction of genes from both sides of follicle (oocyte and GCs) and the ligand-receptor pairs from these two sides. Our data were very comprehensive to uncover the difference between these two populations regarding the folliculogenesis. First, we identified a set of potential genes in oocyte and GCs as the marker genes which can be used to determine the goat fertility capability and ovarian reserve ability. The data showed that GRHPR, GPR84, CYB5A and ERAL1 were highly expressed in oocyte while JUNB, SCN2A, MEGE8, ZEB2, EGR1and PRRC2A were highly expressed in GCs. We found more functional genes were expressed in oocytes and GCs in high fertility group (HL) than that in low fertility group (LL). We uncovered that ligand-receptor pairs in Notch signaling pathway and transforming growth factor-ß (TGF-ß) superfamily pathways played important roles in goat folliculogenesis for the different fertility population. Moreover, we discovered that the correlations of the gene expression in oocytes and GCs at different stages in the two populations HL and LL were different, too. All the data reflected the gene expression landscape in oocytes and GCs which was correlated well with the fertility capability.

scRNA-seq of ovarian follicle granulosa cells from different fertility goats reveals distinct expression patterns.

The new technology of high-throughput single-cell RNA sequencing (10 × scRNA-seq) was developed recently with many advantages. However, it was not commonly used in farm animal research. There are few reports for the gene expression of goat ovarian follicle granulosa cells (GCs) during different developmental stages. In the current investigation, the gene expression of follicle GCs at different stages from two populations of Ji'ning grey goats: high litter size (HL; ≥3/L; 2 L) and low litter size (LL; ≤2 /L; 2 L) were analysed by scRNA-seq. Many GC marker genes were identified, and the pseudo-time showed that GCs developed during the time course which reflected the follicular development and differentiation trajectory. Moreover, the gene expression difference between the two populations HL versus LL was very clear at different developmental stages. Many marker genes differentially expressed at different developmental stages. ASIP and ASPN were found to be highly expressed in the early stage of GCs, INHA, INHBA, MFGE8 and HSD17B1 were identified to be highly expressed in the growing stage of GCs, while IGFBP2, IGFBP5 and CYP11A1 were found to be highly expressed in late stage. These marker genes could be used as reference genes of goat follicle GC development. This investigation for the first time discovered the gene expression patterns in goat follicle GCs in high- or low-fertility populations (based on litter size) by scRNA-seq which may be useful for uncovering the oocyte development potential.

Heavy metals interfere with plasma metabolites, including lipids and amino acids, in patients with breast cancer.

The aim of the present study was to examine the association between plasma heavy metals and the metabolome in patients with breast cancer (BC), and the association with cancer development. Nuclear magnetic resonance was used to determine the metabolites involved and an inductively coupled plasma mass spectrometry system was used to quantify the heavy metals in the plasma samples. It was indicated that cadmium was significantly higher in the plasma of patients with BC compared with that in the control population (~15-fold increase). Chromium, arsenic and lead were also elevated in the plasma of patients with BC by ~3.24, 2.14 and 1.52 fold, respectively. A number of small molecules, including amino acids and salts, were altered in the plasma of patients with BC compared with the control population. Another notable finding in this investigation was that plasma lipid levels were elevated in patients with BC compared with those in the control population. The findings of the present study suggest that exposure to heavy metals, including cadmium, arsenic, chromium and lead, may influence blood lipid levels and other small molecule metabolites, which in turn may be involved in BC development. Further studies surrounding urinary heavy metals and the metabolome are required to further determine the impact of metals on metabolism and on BC development.

Evaluation of heavy metals and metabolites in the urine of patients with breast cancer.

Epidemiologic studies demonstrated that the environment serves a crucial role in cancer development. Heavy metals, including arsenic (As), cadmium (cd), chromium (Cr), lead and mercury, are considered to be carcinogens or co-carcinogens. Furthermore, Cd has been detected in breast cancer (BC) tissue at high concentrations. The present study aimed to investigate the correlation between heavy metals detected in urine and urine metabolome of patients with BC, and their association with cancer development. Nuclear magnetic resonance was used to determine urine metabolites and an inductively coupled plasma mass spectrometry system was used to detect heavy metals in urine samples. The results demonstrated that Cd was markedly increased in the urine of patients with BC compared with the control population (approximately 2-fold). Cr and As were also increased in the urine of patients with BC. In addition, numerous small molecule metabolites were altered in the urine of patients with BC compared with the control population. This study also demonstrated that alterations in small molecule metabolites in the urine of patients with BC were very similar to results from a previous report. These findings indicated that environmental exposure to Cd, As, or Cr could influence the urine levels of metabolites, which may be involved in BC development. Further investigation is therefore required to examine a larger range of samples from different countries or areas in order to understand the impact of heavy metals on metabolism and BC development.

Pubertal exposure to low doses of zearalenone disrupting spermatogenesis through ERα related genetic and epigenetic pathways.

Endocrine disruptor zearalenone (ZEA) has been found to damage the reproductive system especially spermatogenesis. In our previous report, we have found that low dose (lower than No-Observed Effect Level, NOEL) ZEA exposure disturbed mouse spermatogenesis and diminished mouse semen quality. The purpose of current investigation was to explore the underlying mechanisms of pubertal low dose ZEA exposure upsetting spermatogenesis. And it was demonstrated that pubertal low dose ZEA exposure disrupted the meiosis process and the important genetic pathways to inhibit the spermatogenesis and even to diminish the semen quality with the decrease in spermatozoa motility and concentration. The DNA methylation markers 5mC and 5hmC were decreased, the histone methylation marker H3K27 was increased, at the same time estrogen receptor alpha was diminished in mouse testis after pubertal low dose ZEA exposure. The data indicate that the disruption in spermatogenesis by pubertal low dose ZEA exposure may be through the alterations in genetic and epigenetic pathways, and the interactions with estrogen receptor signaling pathway. Therefore, we should pay great attention on ZEA exposure to reduce its adverse impacts on male reproductive health.

Gestational exposure to low-dose zearalenone disrupting offspring spermatogenesis might be through epigenetic modifications.

Zearalenone (ZEA), a F-2 mycotoxin produced by Fusarium, has been found to be an endocrine disruptor through oestrogen receptor signalling pathway to impair spermatogenesis. The disruption on reproductive systems by ZEA exposure might be transgenerational. In our previous report, we have found that low dose (lower than no-observed effect level, NOEL) of ZEA impaired mouse spermatogenesis and decreased mouse semen quality. The purpose of the current investigation was to explore the impacts of low-dose ZEA on spermatogenesis in the offspring after prenatal exposure and the underlying mechanisms. And it demonstrated that prenatal low-dose ZEA exposure disrupted the meiosis process to inhibit the spermatogenesis in offspring and even to diminish the semen quality by the decrease in spermatozoa motility and concentration. The DNA methylation marker 5hmC was decreased, the histone methylation markers H3K9 and H3K27 were elevated, and oestrogen receptor alpha was reduced in the offspring testis after prenatal low-dose ZEA exposure. The data suggest that the disruption in spermatogenesis by prenatal low-dose ZEA exposure may be through the modifications on epigenetic pathways (DNA methylation and histone methylation) and the interactions with oestrogen receptor signalling pathway. Moreover, in the current study, the male offspring were indirectly exposed to low-dose ZEA through placenta and the spermatogenesis in offspring was disrupted which suggested that the toxicity of ZEA on reproductive systems was very severe. Therefore, we strongly recommend that greater attention should be paid to this mycotoxin to minimize its adverse impact on human spermatogenesis.