New research indicates that small RNA in sperm controls the development of an embryo and is necessary for successful embryo implantation in the uterus. These findings have important implications for optimising fertility treatments.
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Infertility causes enormous emotional pain, which can impact every aspect of an affected couple's life. It is increasingly common, with around 90 000 000 couples around the world struggling to conceive.
There are multiple issues that can affect a couple’s chances of conceiving, although sometimes the cause is not obvious. Reproductive technologies are constantly being improved and the success of assisted human reproduction is steadily improving.
Although there are numerous fertility options available to help people who cannot conceive naturally, the two main types are assisted insemination and in vitro fertilisation (IVF).
Since the first successful birth after IVF 40 years ago, use of the technique has escalated. In 2010, there were 1,221 assisted reproduction cycles conducted per million inhabitants in Europe.
Research studies into assisted reproductive technologies and the development of new techniques have greatly improved our understanding of mammalian fertilization and reproduction.They have also provided greater insight into genetic and epigenetic inheritance patterns.
Although the contributions of mammalian females to their offspring, such as nuclear and mitochondrial DNA, are apparent, there are much fewer data regarding male contributions.
Further information regarding the genetic contribution of a father to their offspring were recently discovered and published in two studies that were published today in the journal Developmental Cell.
The first study assessed the small RNA content of sperm during the two weeks between leaving the testis and reaching the vas deferens, from where ejaculation occurs. It showed that the RNA within sperm changes dramatically during this time.
Of particular interest was the finding that some of the RNA found in sperm was transferred to sperm cells from the paternal epididymis. This provides evidence for soma-to-germline information transfer in mammals.
The second study investigated the effect of sperm small RNAs on the function of the sperm itself and of that of the zygote. The results indicated that the small RNAs in sperm are essential for the normal pre-implantation development of the zygote.
The researchers showed that sperm harvested from the epididymis in the very early stages exhibited dramatic misregulation of several RNA and other epigenetic regulators. Eggs fertilized using these sperm failed to produce embryos that successfully implanted in the uterus wall.
The levels and types of small RNA in the sperm are thus critical for successful conception.
This research is vitally important because of the increasing use of assisted reproduction. A substantial subset of embryos are created using fertilization with testicular sperm, which have dramatically different RNA contents from ejaculated sperm.”
Oliver J Rando, Senior Author
The researchers will now investigate whether children conceived naturally show increased disease risk throughout their lifetime.
University of Massachusetts Medical School Press release 26 July 2018.
Sharma et al. Small RNAs are trafficked from the epididymis to developing mammalian sperm. Developmental Cell 2018.
Conine et al. Small RNAs gained during epididymal transit of sperm are essential for embryonic development in mice. Developmental Cell. 2018.