Past highlights
Highlight of November 2015
A commercial human protamine-2 antibody used in several studies to detect mouse protamine-2 recognizes mouse transition protein-2 but not protamine-2
Matthias Eckhardt and Lihua Wang-Eckhardt
Mol. Hum. Reprod. (2015) 21 (11): 825-831. doi: 10.1093/molehr/gav046
This month’s highlight is a very different subject to usual. Increasingly, we are becoming acutely aware that the repeatability of experiments is not an absolute given. There are a plethora of studies now showing that original findings are not easily repeated for various reasons. One reason is the methods used. How reliable are they? For a number of methods, the cornerstone aspect is a well characterised antibody.
Eckhardt and colleagues have examined the specificity of a commercially available antibody to human protamine 2. The results are surprising and I won’t spoil the surprise by telling them here. What is clear, though, is that authors and journals need to pay more attention to the methods used for experiments: how robust are they?
In the ESHRE journals, we are meeting these challenges head on by asking reviewers to pay particular attention to the methods section. Importantly we are also open to publication of negative and/or contradictory data, so that the real answers to study questions are uncovered.
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Highlight of October 2015
Novel characterization of the HSPA2-stabilizing protein BAG6 in human spermatozoa
Elizabeth Bromfield, R. John Aitken, and Brett Nixon
Mol. Hum. Reprod. (2015) 21 (10): 755-769 doi:10.1093/molehr/gav041
Whilst sperm dysfunction is the single most common cause of male infertility currently there is no drug a man can take or that can be added to his sperm in vitro to improve fertility. A fundamental problem with developing new therapies has been the limited understanding of the physiological workings of the normal and dysfunctional spermatozoon.
In their study, Bromfield and colleagues further examine the molecular details of the complexes on the spermatozoa involved in fertilisation, particularly the interaction with the zona pellucida. Previous studies have identified the key role of a molecular chaperone, HSPA2, and the current paper identifies a role for a further protein, BAG6, which changes localisation during capacitation and has defective expression in the spermatozoa of men with specific sperm-zona abnormalities. The exact function of BAG6 has yet to be determined but a role in the successful expression of HSPA2 is suggested. This work is important as it provides essential detailed molecular characterisation of the sperm interaction with the egg: a black box of knowledge despite 35 years of IVF.
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Highlight of September 2015
Functional disparity between human PAWP and PLCζ in the generation of Ca2+oscillations for oocyte activation
Michail Nomikos, Jessica R. Sanders, Junaid Kashir, Randa Sanusi, Luke Buntwal, Daniel Love, Peter Ashley, David Sanders, Paul Knaggs, Adnan Bunkheila, Karl Swann, and F. Anthony Lai
in Mol. Hum. Reprod. (2015) 21 (9): 702-710 doi:10.1093/molehr/gav034
What in the sperm stimulates the egg to get excited and resume development? A key experiment in this arena is the injection (or production) of sperm factor(s) and subsequent examination of calcium oscillations in the egg. So what is the sperm factor? Until recently the answer was a resounding PLCζ. However another candidate PAWP (a post-acrosomal sheath WW domain-binding protein ) has been proposed as an alternative. The debate is a very topical and sometimes heated. In this paper, Lai and colleagues perform a series of experiments producing, for example, recombinant proteins from both candidates. Significant disparities between previous results using PAWP were observed leading the authors to conclude that PAWP was neither sufficient nor necessary for stimulation of calcium oscillations. The debate is likely to continue and it will be interesting to see results of the knock-out mouse.
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Highlight of August 2015
Expression and characterization of three Aurora kinase C splice variants found in human oocytes
Jessica E. Fellmeth, Derek Gordon, Christian E. Robins, Richard T. Scott, Jr, Nathan R. Treff, and Karen Schindler
in Mol. Hum. Reprod. (2015) 21 (8): 633-644 first published online May 20, 2015 doi:10.1093/molehr/gav026
Aneuploidy in oocytes is a fundamental problem in human reproduction. It’s critical we understand the process and consequently what goes wrong. Using information from the mouse as a starting point, Schindler and colleagues, performed a comprehensive study in human oocytes examining the expression and characterisation of Aurora kinase splice variants. They examined these in human oocytes and importantly, using in-vitro experiments, examined the relative importance of each variant. Interestingly, the expression of all three leads to fewer abnormalities in the fidelity of meiosis.
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Highlight of July 2015
Proteolytic processing of anti-Müllerian hormone differs between human fetal testes and adult ovaries
L.S. Mamsen, T.S. Petersen, J.V. Jeppesen, K. Møllgård, M.L. Grøndahl, A. Larsen, E. Ernst, C. Oxvig, A. Kumar, B. Kalra, and C.Y. Andersen
in Mol. Hum. Reprod. (2015) 21 (7): 571-582. doi: 10.1093/molehr/gav024
A plethora of papers examine the role and potential clinical usefulness of Anti-Müllerian hormone (AMH) in the female. In fact, assessment of AMH has become a centre of attention particularly in ART clinics. The study by Andersen and colleagues takes a different approach; by using a series of antibodies, they examine the distribution of mature and immature forms of the hormone. It turns out that there is a very tight regulation of the processing of AMH which may be key to its different roles in males and females.
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Highlight of June 2015
Oxidative stress and human spermatozoa: diagnostic and functional significance of aldehydes generated as a result of lipid peroxidation
Ryan Moazamian, Ashley Polhemus, Haley Connaughton, Barbara Fraser, Sara Whiting, Parviz Gharagozloo, and Robert John Aitken
in Mol. Hum. Reprod. first published online April 2, 2015doi:10.1093/molehr/gav014
Sperm dysfunction, where sperm is present but not fully functional, is the single most common cause of infertility. Yet remarkably, we have no real diagnosis for this condition let alone an effective non-ART treatment. Future developments lie in understanding the function of the normal and the dysfunctional cell. John Aitken and colleagues have pioneered the investigation of oxidative stress in sperm function for the last 25 years. In this study, they present a molecular analysis of the consequences of oxidative stress and suggest a potential robust biomarker for diagnosing this condition.
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Highlight of May 2015
PLCζ or PAWP: revisiting the putative mammalian sperm factor that triggers egg activation and embryogenesis
Junaid Kashir, Michail Nomikos, Karl Swann, and F. Anthony Lai
in Mol. Hum. Reprod. first published online February 26, 2015doi:10.1093/molehr/gav009
How does a sperm, at about 1/500,000th the volume of a human egg, stimulate it to wake up and resume activity? The massive differences in volumes are amazing. I think of it as equivalent to a man walking into a football stadium. With this analogy, what’s even more remarkable is that it’s a very small portion of the man which is required for the wake up call, akin to his credit card. But the presence of a credit card is not enough; the egg is only interested in the size of the credit limit. The egg is activated only by a minuscule protein, but it is one which must be very potent. This protein has usually been identified as a variant of phospholipase C (PLC zeta). It's a remarkable protein and the evidence for it being the primary sperm factor is substantial. However, recently another protein has emerged on the scene and although the evidence is less robust, it's gaining traction. In this issue of MHR, Tony Lai and colleagues discuss the fundamental questions surrounding the discovery of sperm factor(s) and point to the critical experiment which is still necessary before a protein can be legitimately described as the key factor for stimulating the egg to wake up.
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Highlight of April 2015
Intra-sample heterogeneity of sperm DNA methylation Timothy G. Jenkins, Kenneth I. Aston, Cooper Trost, Jordan Farley, James M. Hotaling and Douglas T. Carrell in Mol. Hum. Reprod. (2015) 21 (4): 313-319. doi: 10.1093/molehr/gau115
The critical question when performing an experiment is how robust is the data. Remarkably often this is ignored. In a detailed analysis, Doug Carrell and his group have examined a fundamental question in sperm biology. What are the differences in the sperm epigenome between ejaculates from the same man and between different men? Reassuringly there were consistent results between and within men. However, interestingly within different populations (good and poor sperm) in an ejaculate, there were clear differences. This suggests that poor quality sperm cells have a different imprint to high quality cells. This is perhaps important food for thought for ART populations.
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Highlight of March 2015
Kinetics of human sperm acrosomal exocytosis C.M. Sosa, M.A. Pavarotti, M.N. Zanetti, F.C.M. Zoppino, G.A. De Blas, and L.S. Mayorga in Mol. Hum. Reprod. (2015) doi:10.1093/molehr/gau110
The acrosome reaction (AR) is a unique and essential event for fertilisation. However recently there has been a significant reevaluation of where and how the process occurs. We used to believe for example that the AR was induced by the zona. Now we know that the functional AR occurs prior to zona interaction. In this issue of MHR, Sosa and colleagues address the question of how the process occurs. In a beautifully detailed study using a series of techniques such as transmission electron microscopy, the kinetics of this process are revealed for the first time.
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Highlight of February 2015
1- Subcellular localization of phospholipase C delta in human sperm and its absence in DPY19L2-deficient sperm are consistent with its role in oocyte activation Escoffier et al in Mol. Hum. Reprod. (2014) doi: 10.1093/molehr/gau098
2- Dpyl12-deficient globozoospermic sperm display altered genome packaging and DNA damage that compromises the initiation of embryo development Yassine et al in Mol. Hum. Reprod. (2014) doi: 10.1093/molehr/gau099
This month’s highlight is very different. I’ve picked 2 papers from the same group. Why? These studies address the rare but fascinating pathology known as globozoospermia. Before the discovery of DPLY2 as a deletion that causes globozoospermia (in a significant number of cases) our knowledge of this condition was spare. However now there has been a minor explosion in our understanding of this condition and these two papers make a very significant contribution to the field. They use both a mouse model and humans to try and understand what goes wrong in globozoospermia… fascinating biology.
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Read article 2>
Highlight of January 2015
The mitochondrion, its genome and their contribution to well-being and disease Justin C. St. John, Mol. Hum. Reprod. (2015) 21 (1): 1-2. doi: 10.1093/molehr/gau085
This issue of MHR includes a series of articles discussing the increasing importance of mitochondria, not just to reproduction but also to the onset of common diseases. The subject is very topical as there is increasing pressure, due to the severe effects on mitochondrial disorders, to use ART technologies to help relieve the burden of disease. Primarily, this focusses on replacement of the abnormal mitochondria with healthy ones by using, for example, pronuclear transfer. Whilst exciting, these technologies need to be adopted with great care. The reviews in this issue of MHR, including the editorial by Jus St John, highlight the questions that remain to be addressed.
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Highlight of December 2014
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!
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Highlight of November 2014
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.
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Highlight of October 2014
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.
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Highlight of August 2014
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.
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Highlight of June/July 2014
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.
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Highlight of May 2014
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.
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Highlight of April 2014
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.
Highlight of March 2014
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
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Highlight of February 2014
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.
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Highlight of January 2014
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…
Highlight of December 2013
MHR : Basic Science of Reproductive Medicine - Volume 19, Issue 12, December 2013
Tribute to Robert Edwards
The December issue of MHR is a Celebration issue in tribute to Professor Sir Robert Edwards. It consists of an editorial and seven papers all freely available. Three invited reviews from eminent scientists summarise Bob Edward’s landmark findings in oocyte maturation, ovulation and sperm capacitation and describe the state-of-the-art today and the challenges for the future.
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Highlight of November 2013
MHR : Basic Science of Reproductive Medicine - Volume 19, Issue 11, November 2013
As summarized in their Editorial ‘MHR welcomes high quality basic reproductive research around pregnancy’ MHR Associate Editors Professor Jane Norman and Associate professor Stephen Tong welcome the fact that MHR’s interest does not stop at implantation, but straddles all of pregnancy.
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Highlight of October 2013
Widespread DNA hypomethylation at gene enhancer regions in placentas associated with early-onset pre-eclampsia - Mol. Hum. Reprod. (2013) 19 (10): 697-708. doi: 10.1093/molehr/gat044 by J.D. Blair, R.K.C. Yuen, B.K. Lim, D.E. McFadden, P. von Dadelszen and W.P. Robinson
Early onset pre-eclampsia (EOPET) is a severe form of pre eclampsia which is a serious complication of pregnancy. With the ever increasing awareness of the importance of epigenetics Blair and colleagues studied DNA methylation in specific regions (gene enhancers) of the placentas associated with EOPET. Following on from their previous studies they increased the number of samples and importantly used a comprehensive microarray screening system interrogating 99% of know genes. They found that there were widespread methylation changes associated with EOPET which may be associated with placental function. Although further data is needed it raises the possibility of a non-invasive prenatal diagnosis of at-risk pregnancies – a very welcome development.
Read the article here
Highlight of September 2013
Functional human sperm capacitation requires both bicarbonate-dependent PKA activation and down-regulation of Ser/Thr phosphatases by Src family kinases - Mol. Hum. Reprod. (2013) 19 (9): 570-580 doi:10.1093/molehr/gat033 by M.A. Battistone, V.G. Da Ros, A.M. Salicioni, F.A. Navarrete, D. Krapf, P.E. Visconti, and P.S. Cuasnicú
In order to fertilise the egg it is essential that the spermatozoon is capacitated. This was discovered in the early 1950’s yet we are still trying to determine the molecular details of this pivotal event. Battistone and colleagues have addressed a key part of the puzzle concentrating on how the cell initiates capacitation (within the first few minutes). In humans they investigated the activation of protein kinase A (PKA) (by bicarbonate) with specific emphasis on the modulating role of Ser/Thr phosphatases. Using a series of inhibitors they demonstrate that the initial activation of PKA substrates was dependent on an inhibition of the phosphatases by Src family kinases. This shows a very delicate control pattern which helps clarify the complex biochemical pathways involved in capacitation. This type of information deepens our understanding whilst at the same time offering potential avenues of manipulation for the putative non ART treatment of sperm dysfunction.
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Highlight of August 2013
Mode of oocyte maturation affects EGF-like peptide function and oocyte competence - Mol. Hum. Reprod. (2013) 19 (8): 500-509. doi:10.1093/molehr/gat028 by D. Richani, L.J. Ritter, J.G. Thompson, and R.B. Gilchrist
The successful maturation of oocytes in vitro (IVM) is a major goal in ART that has yet to be reliably achieved. Richani and colleagues examined the role of the Epidermal Growth Factor (EGF) signalling pathway during mouse IVM. Supplementation of media with EGF like peptides (amphiregulin and epiregulin) significantly improved oocyte competence. Whilst there is a long way to go to obtain defined media producing a robust response in humans, this is a significant step along this tortuous pathway.
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Highlight of July 2013
Genetic dissection of the pre-eclampsia susceptibility locus on chromosome 2q22 reveals shared novel risk factors for cardiovascular disease - Mol. Hum. Reprod. (2013) 19 (7): 423-437 doi:10.1093/molehr/gat011 by M.P. Johnson and co-workers
Pre-eclampsia is a serious and relatively common complication of pregnancy. An association between pre-eclampsia and later life cardiovascular disease (CVD) has been established providing a compelling reason to investigate the genetic risk factors involved in pre eclampsia. Johnson and colleagues performed a comprehensive and detailed assessment of susceptibility loci on chromosome 2q22. Novel SNP associations with pre-eclampsia and a number of CVD related traits are reported providing evidence for shared genetic mechanisms underlying pre eclampsia and CVD.
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Highlight of June 2013
DPY19L2 gene mutations are a major cause of globozoospermia: identification of three novel point mutations - Mol. Hum. Reprod. (June 2013) 19(6): 395-404 doi:10.1093/molehr/gat018 by Fuxi Zhu, Fei Gong, Ge Lin, and Guangxiu Lu
Globozoospermia (round headed spermatozoa) is a rare heterogeneous condition. Men are sterile unless ICSI is used as a treatment option. In 2010 a homozygous deletion of a ~200kb region encompassing the DPY19L2 gene was identified as a significant cause. Following this there have been several confirmatory reports but as the condition is rare our knowledgebase on the condition and its causes is very limited. The paper by Zhu and colleagues examines 14 patients with complete globozoospermia, confirms that deletion of DPY19L2 is a cause in 4 cases and significantly identifies 5 patients with homozygous mutations (the remaining 5 had no identified mutation). These findings add a considerable amount of data – including novel mutations - on a rare condition, thus enhancing the possibility of relating genotypic variation with reproductive success and potentially providing a robust diagnostic marker.
Read the article here
Highlight of May 2013
Molecular cloning and analysis of the Catsper1 gene promoter - Mol. Hum. Reprod. (May 2013) doi: 10.1093/molehr/gat003 by Minerva Mata-Rocha, Edith Alvarado-Cuevas, Javier Hernandez-Sanchez, Doris Cerecedo, Ricardo Felix, Adriana Hernandez-Reyes, Emiliano Tesoro-Cruz, and Norma Oviedo
Sperm motility is critical for fertility yet the mechanisms underlying it are poorly understood. However technological developments in imaging and calcium signalling are revolutionising our understanding. A key channel involved in controlling calcium entry into the cell is CatSper. Sperm from mice null for CatSper show reduced progressive motility and fail to hyperactivate rendering them incapable of fertilization. CatSper genes are exclusively expressed in the testis during spermatogenesis. However their role in human infertility has yet to be delineated. Minerva Mata Roca and Norma Oviedo and team from Mexico have provided an important new insight into this problem. Using a variety of techniques including in vitro and in vivo transcription studies they have characterised the promoter region of CatSper 1 – in mice and humans. This will provide key information for future studies of the regulation of the Catsper channel in germ cells and a strong foundation for better understanding of the mechanisms of sperm motility and fertilization.
Read the article here
Highlight of April 2013
The search for biomarkers of human embryo developmental potential in IVF: a comprehensive proteomic approach Mol. Hum. Reprod. (2013) 19(4): 250-263 doi:10.1093/molehr/gas063 by Nyalwidhe J., Burc T., Bocca S., et al.
Concomitant with the development of single embryo transfer has been the absolute requirement to select the best embryo for transfer. Whilst there have been many attempts to do this, new technologies have yet to be robustly tested. Sergio Oehninger and colleagues present novel data on the non-invasive assessment of expressed proteins/peptides using proteomics. Using culture media from day 3 embryos up to 14 differentially regulated peptides were identified. Multiple algorithms enabled significant association with pregnancy and implantation failure. This data is potentially very useful. Whilst independent studies are now required, perhaps the power of this type of technology is eventually being realised.
Read the article here
Highlight of March 2013
Investigation of the mechanisms by which the molecular chaperone HSPA2 regulates the expression of sperm surface receptors involved in human sperm–oocyte recognition, Mol. Hum. Reprod. (2013) 19(3): 120-135 doi:10.1093/molehr/gas064 by Kate A. Redgrove, Amanda L. Anderson, Eileen A. McLaughlin, Moira K. O'Bryan, R. John Aitken and Brett Nixon
Remarkably, despite decades of research, the molecular details of how a human sperm interacts with an egg remains somewhat of a mystery. Now a paper published in Molecular Human Reproduction by Redgrove and colleagues from Australia provides a unique insight into this fundamental interaction. The human sperm, during its expression of fertilising capacity (a feature termed capacitation) exposes a series of proteins that allow the exposure on the head of the sperm of a key complex including arylsulfatase A which may be important for sperm zona interaction. This work emphasis the dynamic nature of the sperm plasmamebrane and identifies potential functions of multimeric protein complexes in the spermatozoon.
Read the article here
Highlight of February 2013
Galectin-1 influences trophoblast immune evasion and emerges as a predictive factor for the outcome of pregnancy by Tirado-González I, Freitag N, Barrientos G, et al. Mol Hum Reprod 2013; 19: 43-53.
Remarkably, despite decades of research, the molecular details of how a human sperm interacts with an egg remains somewhat of a mystery. Now a paper published in Molecular Human Reproduction by Redgrove and colleagues from Australia provides a unique insight into this fundamental interaction. The human sperm, during its expression of fertilising capacity (a feature termed capacitation) exposes a series of proteins that allow the exposure on the head of the sperm of a key complex including arylsulfatase A which may be important for sperm zona interaction. This work emphasis the dynamic nature of the sperm plasmamebrane and identifies potential functions of multimeric protein complexes in the spermatozoon.
Read the article here.