Comment:One of the best mailout this year with reports on age of media, pesticide impacts on semen profile and further inputs onto the nature of sperm induced oocyte activation. For me, the pesticide article is very thought provoking and warrants being read by many who do semen analysis. Thinking of going organic just on this article.
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Superovulation Using the Combined Administration of Inhibin Antiserum and Equine Chorionic Gonadotropin Increases the Number of Ovulated Oocytes in C5
In this study, we examined the effect of IAS and eCG on the number of ovulated oocytes in immature female mice of the C57BL/6 strain in superovulation treatment. Furthermore, we evaluated the quality of obtained oocytes produced by superovulation using IASe by in vitro fertilization (IVF) with sperm from C57BL/6 or genetically engineered mice.
Transglutaminase 4 as a prostate autoantigen in male subfertility
In the mouse, we further link TGM4 immunity with a destructive prostatitis and compromised secretion of TGM4. Collectively, our findings in APS1 patients and Aire-deficient mice reveal prostate autoimmunity as a major manifestation of APS1 with potential role in male subfertility.
Live birth rates after MESA or TESE in men with obstructive azoospermia: is there a difference?
When adjusted for the available confounders, the odds ratio for live birth was significantly in favour of MESA-ICSI versus TESE-ICSI (OR 1.82: 95% CI 1.05–3.67). Our study suggests that some aspect of sperm maturation after the sperm leaves the testicle to enter the epididymis is required for the most optimal results, even when ICSI is used for fertilization.
Fruit and vegetable intake and their pesticide residues in relation to semen quality among men from a fertility clinic
To our knowledge, this is the first report on the consumption of fruits and vegetables with high levels of pesticide residue in relation to semen quality. Further confirmation of these findings is warranted.
Age of G-1 PLUS v5 embryo culture medium is inversely associated with birthweight of the newborn
Age of G-1 PLUS v5 medium used to culture human embryos affects birthweight of the respective newborn. This could imply that the preimplantation embryo adapts to its in vitro environment with lasting in vivo consequences. Therefore, it is important that companies are transparent about the exact composition of their embryo culture media, which will allow IVF clinics to further investigate the effects of the media or media components on the health
If demographic trends towards later fatherhood continue, this will likely lead to a more children suffering from genetic disorders. A trend of later fatherhood will accelerate the accumulation of paternal-origin de novo mutations in the gene pool, gradually reducing human fitness in the long term. These risks suggest that paternal age is of ethical importance.
PLCζ: or PAWP: revisiting the putative mammalian sperm factor that triggers egg activation and embryogenesis
Recent data have emerged suggesting the sperm factor may be a post-acrosomal sheath WW domain-binding protein (PAWP). However, a significant body of research points to a testis-specific phospholipase C zeta (PLCζ:) as the sperm factor. Herein, we examine the evidence presented in favour of PAWP in relation to PLCζ: and the requisite physiological properties of the mammalian sperm factor.
Functional disparity between human PAWP and PLCζ:: in the generation of Ca2+ oscillations for oocyte activation
Thus, the functional disparity with PLCζ:: leads us to conclude that human PAWP is neither sufficient nor necessary for the Ca2+ oscillations that initiate mammalian oocyte activation following fertilization.
Successful ovulation of 100 eggs from one female mouse
A new method of controlled ovarian hyperstimulation, termed ultra-superovulation, has been developed by researchers in which ovulation of a very large number of eggs from one female mouse occurs. This development makes it possible to analyze gene function more efficiently through mass production of knockout mice.
The sperm of all 18-year-olds should be frozen for use in later life because of the risks attached with being an older father, a UK bioethicist has argued. Sperm becomes more prone to errors with age, increasing the risk of autism, schizophrenia and other disorders.
In this interesting study, Kleijkers, et.al looked at the age from production to use and found that the older the media, the lower the birthweight of infants born.
Comment
The authors looked at the age of culture media not from date of opening but from date of production and found that the older the media was had no effect on fertilisation and cleavage rates, on embryo quality nor on ongoing pregnancy rate. |By using data over many years and adjusting for confounding factors, media age of more than 65 days was associated with a deceased birthweight of 234 gms. This may be a set of data media manufacturers would find difficult to access and monitor and as the article indicates, may not be representative of all media.| However, since most media is similar, there would be an expectation that their observations could be similar. The point is that while concerns of media effects on large babies have been often implied (from cattle work), this data suggests that aging of media may influence energy substrates rather than protein. The concern expressed by the authors is that this demonstrates in vitro effects can have in vivo consequences. However, the age of the media at use is a clinic liability. Many clinics order large bottles of media to avoid costs and are often used right up to the expiry date. Almost certainly, few if any clinics monitor the age of the media apart from the use by date and few would have foreseen this outcome. |Given relationships between birthweight and adult well-being and health, clinics may need to review their management of media and their supply chain to minimise excessive storage. If a couple asked what age of media was used for their attempt, few clinics could easily reply since it is not a common KPI or cycle statistic. This article suggest it would be worthwhile to do so in the future.
Title
Diet Toxicity and Male Fertility
Summary
Semen profile fall when there is a high dietary of foods with a known high levels of pesticide residues in fruit and vegetables
Comment
A worrisome article that shows decreased semen profiles in relation to an increased consumption of fruit and vegetables of known pesticide contamination. We are all told to eat more fruit and vegetables but did you know that there are tables in the US retailing the level of pesticides in each food type. In this article(s), Chavarro, et. al. carried out a food consumption survey of 155 men from which they calculated the number of daily serves of fruit and vegetables and then from the pesticides contamination tables calculated their total pesticide exposure in relationship to a single semen analysis. | They showed significant declines in concentration, motility and morphology in the group having the highest exposure risk. Conversely, they also noted in the group of men with the highest number of daily serves but with food of low contamination, significantly better semen profiles. |The differences they reported would reflect poorly in a semen analysis and have the potential to result in samples falling below the normal range. This implies that any adverse semen profile may have some origins in diet. It supports an argument that infertile males or males in an infertile relationship may benefit from moving to a diet with a high number of daily serves of ORGANIC fruit and vegetables. Maybe we should all do this but for men with a poor semen profile especially so.| Many in the IVF field just ignore the reasons why a man may be infertile assuming IVF will solve the problem of pregnancy. This article reminds us that for many couples, their infertility may be resolved in less technological ways and more attention paid to lifestyle be warranted.|
Title
Resolving egg activation at fertilization
Summary
In mammals, egg activation involves a series of calcium concentration changes (or ‘oscillations’). These oscillations are considered to be caused by a ‘sperm-specific protein factor’.
Comment
| Resolving egg activation at fertilization: ‘Oh sperm factor! Wherefore art thou?’ |
Junaid Kashir, Michail Nomikos, Karl Swann & F. Anthony Lai*, Cardiff University School of Medicine, Cardiff, UK |
*Email: LaiT@cf.ac.uk ||
The fundamental event during creation of a new human is when the male’s fertilising sperm initiates embryo development by ‘activating’ the female egg. In mammals, egg activation involves a series of calcium concentration changes (or ‘oscillations’). These oscillations are considered to be caused by a ‘sperm-specific protein factor’ that is delivered to the egg following sperm/egg fusion at fertilisation. |
Of the various candidates proposed as the sperm factor thus far, a wide variety of data reported by multiple independent laboratories worldwide have cumulatively been consistent with the proposition that the sperm factor’s identity is a unique phospholipase C (PLC) enzyme, found exclusively within sperm and testes, termed PLC-zeta (PLCz). Injection of laboratory-made PLCz into mammalian eggs produces the same profile of calcium oscillations as occurs during normal fertilisation, while depletion of sperm PLCz abolishes these striking patterns of calcium release. Clinically, patient sperm that repeatedly fails to successfully activate eggs after in vitro fertilisation (IVF) or intra-cytoplasmic sperm injection (ICSI), were found to either possess abnormal forms or reduced/absent levels of PLCz. |
Recently, however, studies from a single laboratory have proposed that the identity of the sperm factor is a different sperm-specific protein, termed post-acrosomal sheath WW domain-binding protein (PAWP), and that this protein represents a more suitable candidate for the sperm factor than PLCz. These PAWP studies purportedly found that laboratory-made PAWP was able to successfully cause calcium release in mammalian eggs, while blocking PAWP with an inhibitory peptide prevented fertilisation from successfully occurring. However, there remain major concerns that require addressing before PAWP becomes a serious candidate for the physiological ‘sperm factor’ (1). The main concern is that we have been unable to reproduce any of the original findings claiming that PAWP can cause calcium oscillations in mouse eggs. We are also unable to find any observable inhibitory effect on fertilization of the PAWP ‘inhibitory’ peptides (2). As far as we know, we are the only group to attempt to replicate the specific findings regarding PAWP. |
Currently, no experimental evidence exists to explain the biochemical context of PAWPs mechanism of action, nor have the specific structural and functional correlates of PAWP’s properties been experimentally determined. It also remains unclear, even from the reports suggesting PAWP can produce calcium release/egg activation, whether PAWP is able to drive subsequent embryogenesis to the blastocyst stage, as has been demonstrated for PLCz. |
At present, a significant body of evidence constituting the majority of research on this topic supports PLCz as the ‘sperm factor’, including analysis of the unique biochemical and structural features of this enzyme, its physiological mechanism of action within mammalian eggs at fertilisation, as well as important clinical relevance, all within the context of egg activation. The reliability of such data is strengthened by complementary PLCz research from multiple laboratories around the world who have confirmed each other’s work independently. | Unfortunately, the same reproducibility does not currently apply to PAWP, where there is no independent confirmatory data available. Thus, at least until independent, novel, and convincing contrary data becomes available in support of a precise role for PAWP in egg activation at fertilization, it would be prudent not to exclude the stronger, well-accepted candidate, PLCz. | |
(1) PLCz or PAWP: revisiting the putative mammalian sperm factor that triggers egg activation and embryogenesis. Junaid Kashir, Michail Nomikos, Karl Swann & F. Anthony Lai. Molecular Human Reproduction 2015(in the press) doi:10.1093/molehr/gav009 - http://www.ncbi.nlm.nih.gov/pubmed/26116451 |
(2) Functional disparity between human PAWP and PLCz 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 & F. Anthony Lai. Molecular Human Reproduction 21(5):383-8, 2015. doi:10.1093/molehr/gav034 - http://www.ncbi.nlm.nih.gov/pubmed/25722320 |
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