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Published on: October 4, 2019
The developmental miR-17-92 cluster and the Sfmbt2 miRNA cluster cannot rescue the abnormal embryonic development
Xunwei Wu1, Xiaomei He1, Qian Liu1
1Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Background:
Sperm, during epididymal transit, acquires microRNAs(miRNAs), which are crucial for embryonic development. However, whether sperm miRNAs influenced by an obstructive epididymal environment affect embryonic development remains unknown.
Method:
The sham operation and vasectomy were performed in C57BL/6 J mice to create the control group (CON) and the obstructive epididymal environment group(OEE) group, respectively. The morphology of the testis and epididymis was observed using hematoxylin and eosin staining (HE staining) to establish the OEE mice model. The sperm quality test, intracytoplasmic sperm injection (ICSI), and epididymosomes fusion were employed to observe the effect of the obstructive epididymal environment on sperm and resultant embryonic development. The alteration of the sperm small RNA (sRNA) profile was analyzed by sRNA sequencing. RT-qPCR and DNA methylation were applied to observe the effect of obstructive epididymis on the expression of sperm miRNAs. The miRNAs microinjection was used to explore the impacts of sperm miRNAs on embryonic development.
Results:
We confirmed postoperative 8-week mice as the OEE mice model by examining the morphology of the testis and epididymis. In the OEE group, we observed that sperm quality degraded and the development potential of embryos was reduced, which can be saved by the normal epididymal environment. The sperm sRNA sequencing revealed that the expression of the developmental miR-17-92 cluster and the Sfmbt2 miRNA cluster was downregulated in the OEE group. The expression of these two miRNA clusters in epididymis was also downregulated and regulated by DNA methylation. However, the downregulation of either the miR-17-92 cluster or the Sfmbt2 miRNA cluster in normal zygotes did not impair embryonic development.
Conclusion:
The obstructive epididymal environment influences sperm quality and resultant embryonic development, as well as the abundance of the developmental miR-17-92 cluster and the Sfmbt2 miRNA cluster in sperm, but these miRNA clusters are not the cause of abnormal embryonic development. It implies that epididymis is important in early embryonic development and may play a potential role in sperm epigenome.
Insights
An obstructive epididymal environment impairs sperm quality and embryonic development. While specific microRNA clusters (miRNAs) are affected, they do not appear to be the direct cause of developmental issues.
Area of Science:
- Reproductive Biology
- Developmental Biology
- Epigenetics
Background:
- Sperm acquire microRNAs (miRNAs) during epididymal transit, which are vital for embryonic development.
- The impact of an obstructive epididymal environment on sperm miRNAs and subsequent embryonic development is not well understood.
Purpose of the Study:
- To investigate how an obstructive epididymal environment affects sperm quality, miRNA profiles, and embryonic development in mice.
- To determine if altered sperm miRNAs in an obstructive epididymal environment are responsible for impaired embryonic development.
Main Methods:
- Established an obstructive epididymal environment (OEE) mouse model using vasectomy.
- Assessed sperm quality, performed intracytoplasmic sperm injection (ICSI), and analyzed sperm small RNA (sRNA) profiles via sequencing.
- Investigated miRNA expression and DNA methylation in the epididymis and sperm.
- Utilized miRNA microinjection to study their direct effects on embryonic development.
Main Results:
- The OEE model showed degraded sperm quality and reduced embryonic development potential, which were reversible with a normal epididymal environment.
- sRNA sequencing revealed downregulation of the miR-17-92 and Sfmbt2 miRNA clusters in sperm from OEE mice.
- These miRNA clusters were also downregulated in the epididymis and regulated by DNA methylation.
- Microinjection of these specific miRNA clusters into normal zygotes did not impede embryonic development.
Conclusions:
- An obstructive epididymal environment negatively impacts sperm quality and embryonic development.
- While specific miRNA clusters (miR-17-92, Sfmbt2) are altered in sperm under obstructive conditions, they are not the cause of abnormal embryonic development.
- This suggests the epididymis plays a crucial role in early embryonic development and potentially in sperm epigenome regulation.
