Sperm competition and the evolution of reproductive systems Steven A. Ramm et al. Mol. Hum. Reprod. (2014) 20 (12): 1159-1160. doi: 10.1093/molehr/gau076

This month MHR publishes an outstanding series of reviews related to the rapidly emerging science of sperm competition. An editorial accompanying these reviews by Steven Ramm and colleagues outlines the key developments in the field. Perhaps those who only study human reproduction are less familiar with the concept, but sperm competition links evolution and reproduction and is the focus of some truly amazing biology. One of the purposes of publishing this series in MHR is to bring the remarkable findings in this field to the readers of the ESHRE journals and thereby encourage some cross hybridisation. Enjoy!

Genomic and proteomic dissection and characterization of the human sperm chromatin Judit Castillo et al. Mol. Hum. (2014) Reprod., doi:10.1093/molehr/gau079

Historically sperm were regarded as simple cells - head and tail. The tail got them to the egg and the head carried the chromosomes... game over.
Now we realised the cell is a complex and highly specialised machine. Rafael Oliva and colleagues have performed a detailed genomic and proteomic analysis of the chromatin structure of the human spermatozoon. This has revealed a highly organised and intricate matrix. The real interest in this approach is the significant potential for an epigenetic signature to be carried by the sperm into the egg. What’s even more interesting is the possibility that their signatures may be relatively easy to disrupt.  

High-resolution helium ion microscopy of epididymal epithelial cells and their interaction with spermatozoa Teodor G. Păunescu et al., Mol. Hum. Reprod. (2014) doi: 10.1093/molehr/gau052

Sperm cells, when they leave the testis, cannot fertilise an egg. They acquire fertilising ability as they pass down the epididymis. The interaction between the sperm and the epididymis is therefore critical. However, we know relatively little about the mechanisms and cellular interactions that take place. Păunescu and colleagues, using high resolution helium ion microscopy, have published some dramatic images of the epididymal epithelium and its intimate interaction with sperm. Whilst these pictures are breath-taking this is not just a picture gallery. This analysis provides a clear evidence of a very intimate interaction between the spermatozoon and the epithelium - a lovely waltz in fact. This is a real breakthrough in technology which will allows us to understand how the sperm acquires fertilising capacity. 

DNA methylome profiling of maternal peripheral blood and placentas reveal potential fetal DNA markers for non-invasive prenatal testing Y. Xiang et al., Mol. Hum. Reprod. (2014) doi: 10.1093/molehr/gau048

During pregnancy there is a tiny proportion of cell-free fetal DNA flowing in the maternal peripheral blood. The ability to resolve this fetal DNA from the maternal background and to analyze its sequence is like a crystal ball that allows us to see into a child’s future. In principle, chromosomal aneuploidies, DNA point mutations and other features of fetal DNA could be revealed. Would they have any predictive value for the child? To answer this question, we first need to define a catalogue of features that can potentially resolve between fetal and maternal DNA. Exploiting the presence of DNA methylation differences between fetal and maternal DNA, Xiang and colleagues applied bisulphite conversion, amplification and sequencing of the DNA fragments, resulting in a genome-wide profiling of the fetal DNA except the Y chromosome. This is a resource that can be mined for new fetal DNA markers, in addition to those already known, which are based on targeted tests for a few dozen genes. Keeping in mind that detected genetic mutations are no guarantee that any specific disease will actually ensue, and that DNA polymorphisms between the ethnic groups add complexity to the analysis, the study of Xiang and colleagues is a shining example of the possibilities of non-invasive prenatal testing.  

Inhibition of phosphatase and tensin homologue (PTEN) in human ovary in vitro results in increased activation of primordial follicles but compromises development of growing follicles Mol. Hum. Reprod. (2014) 20 (8): 736-744. doi: 10.1093/molehr/gau037 M. McLaughlin et al.

A primary goal of human ovarian culture is to obtain a pool of mature oocytes that are able to be fertilised successfully. To achieve it is critical to illuminate the myriad of factors that influence how a follicle within the ovary is stimulated to grow. Previous work in mice has shown that the phosphoinositide 3-kinase-protein kinase B (PI3K-Akt) pathway plays a critical role. Phosphatase and tensin homologue (PTEN) is able to supress this pathway and thus regulate the initiation of follicle growth. In this paper, McLaughlin and colleagues have used a reversible PTEN inhibitor to study the effects of chemically enhanced initiation of follicle growth on human tissue in vitro. Although greater initiation of follicles growth was found compared to the control group, when isolated and cultured, these follicles showed limited growth and decreased survival. These findings demonstrate that a PTEN inhibitor can be used to stimulate the activation of follicles however, obtaining functional oocytes is still some way off. 

Patch clamp studies of human sperm under physiological ionic conditions reveal three functionally and pharmacologically distinct cation channels Mol. Hum. Reprod. first published online January 16, 2014 doi:10.1093/molehr/gau003 S.A. Mansell, S.J. Publicover, C.L.R. Barratt, and S.M. Wilson

Sperm biology has undergone a minor revolution. The successful application of routine development patch clamping to the human spermatozoon in 2010 has resulted in a dramatic increase in our understanding of the workings of the normal cell. In this issue of MHR, Mansell and colleagues have performed a very detailed patch clamp analysis of spermatozoa from normal donors. The primary aim was understanding the regulation of membrane potential focussing on identification and assessment of the potassium conductance. They suggest that the characteristics of the channel are most similar to Slo3 but also provide evidence that the analysis is complicated and there may be at least 3 key cation channels operating. This work will form a platform for the detailed analysis of spermatozoa from sub fertile men identifying for the first time possible ion channel pathologies. 

Double-stranded DNA breaks hidden in the neutral Comet assay suggest a role of the sperm nuclear matrix in DNA integrity maintenance Mol. Hum. Reprod. (2014) 20 (4): 330-340 doi:10.1093/molehr/gat090 J. Ribas-Maynou, J.E. Gawecka, J. Benet, and W.S. Ward 
The observation by Don Evenson, in a seminal paper in Science in 1980, that sperm chromatin structure may be an important indicator of fertility potential in animals and man sparked a wave of papers on the subject. Recently, clinical data indicate that assessment of sperm DNA damage using for example the COMET assay may be important for identifying patients at a higher risk of miscarriage. In this issue of MHR, Ribas-Maynou use a mouse model to provide an in depth understanding of the nature of single and double strand breaks and their detection by the COMET assay. These experiments may lead to new insights into sperm DNA damage in sub-fertile patients and potential improvements/standardisation in the clinical testing procedures. 

Production of fat-1 transgenic rats using a post-natal female germline stem cell line Mol. Hum. Reprod. (2014) 20 (3): 271-281 doi:10.1093/molehr/gat081

Probably, one of the most controversial subjects in reproductive biology is the question over the existence of stem cells in the post natal mammalian ovary. The questions are numerous for example: Are they present?, In what form?, Are they functional? and if so under what conditions? etc..

The subject has attracted, rightly, considerable attention. Studies in 2009 demonstrated that female germline stem cells (FGSCs) had the potential to generate live young in mice although there is data to the contrary. In this issue of MHR the same research group (Zhou and colleagues) show that a FGSC stem cell line could be established from postnatal rat ovaries and, importantly that transgenic rats could be generated using these cells. This is important study as it not only indicates functional oocytes can be produced but it also provides a potentially more effective method to generate transgenic rats! 

The study will generate considerable attention and interested readers should note the editorial commentary by Yuqiong Pan putting this new and exciting work into context.

Editorial: Yuqiong Pan A New Tool To Generate Transgenic Rats Using Female Germline Stem Cells From Postnatal Ovaries Mol. Hum. Reprod. first published online March 7, 2014 doi:10.1093/molehr/gau017 

Gain of 20q11.21 in human embryonic stem cells improves cell survival by increased expression of Bcl-xL, Mol. Hum. Reprod. (2014) 20 (2): 168-177 doi:10.1093/molehr/gat077 

A significant proportion (~25%) of human embryonic stem cell lines have a mutation (gain of 20q11.21) as do induced pluripotent stem cells (~18%). The implication is that the gain of this mutation provides a selective advantage. The mechanisms of this remain to be fully understood. 

Nguyen and colleagues using a series of loss and gain of function experiments showed that expression of an anti-apoptotic factor (Bcl-xL) was a critical factor in the selective advantage of these cells making them resistant to apoptosis. This has important implications not just for stem cell work but also for cancer therapy. 

Claudia Osycka-Salut et al, Cyclic AMP efflux, via MRPs and A1 adenosine receptors, is critical for bovine sperm capacitation, Mol. Hum. Reprod. (2014) 20 (1): 89-99

Sperm capacitation and function is critically depended on cAMP and its associated signalling repertoire. Although the exact details are yet to be clearly established there has been tremendous progress in the last 10 years into delineating the crucial players.
What is particular interesting about this study is that authors examine the role of cAMP extrusion on sperm function. The authors demonstrate that cAMP extrusion was important for sperm capacitation. Importantly they suggest that external cAMP may exert the pro capacitation affect via the A1 adenosine receptor. This is a fascinating scenario which further adds to the complex working of the sperm cell and provides a strong platform for paracrine/autocrine investigation of cAMP. Perhaps sperm do talk to each other and maybe this isn’t just idle gossip…