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Santo Stefano del Sole, Italy

Santella L.,Stazione Zoologica Anton Dohrn | Dale B.,Center for Assisted Fertilization
Reproductive BioMedicine Online

In a recent report in Reproductive Biomedicine Online by Ebner et al., a comprehensive multi-centre study was presented on the use of a calcium ionophore, A23187, to artificially activate oocytes from patients who had poor fertilization rates in previous cycles. Under physiological conditions, the calcium increase in oocytes at activation is caused by influx and release from specific stores and ion channels, and has precise temporal, quantitative and spatial patterns. Calcium ionophores may release Ca2+ in an uncontrolled fashion from intracellular stores that would not normally be involved in the activation process. Ionophores, including A23187, have a multitude of effects on cell homeostasis, not yet defined in oocytes, that may have long-term effects, for example on gene expression. We suspect that the successful births reported by Ebner et al. are a result of the overriding influence of the injected spermatozoa, rather than the effect of the ionophore; nevertheless, such an invasive non-physiological approach to assisted reproduction techniques is worrying, especially as epigenetic effects may result in future generations. © 2015 Reproductive Healthcare Ltd. Source

Dale B.,Center for Assisted Fertilization | Defelice L.,Virginia Commonwealth University
Journal of Assisted Reproduction and Genetics

The purpose of this review is to open a debate as to whether or not oocytes actively repel supernumerary sperm or in nature final sperm : oocyte ratios are so low that polyspermy preventing mechanisms are not necessary. Before encountering the oocyte, spermatozoa need to be primed, either by environmental factors as in animals exhibiting external fertilization, or by factors from the female reproductive tract, as in mammals. The spermatozoon must then recognize and interact with the outer layers of the oocyte and progression of the fertilizing spermatozoon through these layers is further controlled and modulated by a precise sequence of signals in situ. Removal of these outer coats may not inhibit fertilization, however does interfere with the dynamics of sperm-oocyte interaction. We propose that monospermy in mammals and sea urchins, under natural conditions, is ensured by the controlled and gradual encounter of a minimum number of spermatozoa with the oocyte and that fine tuning is ensured by the structural and molecular organization of the oocyte and its surrounding coats. We suggest that laboratory experiments using oocytes deprived of their investments and exposed to unnaturally high concentrations of spermatozoa are artifactual and argue that the conclusions leading to the hypothesis of a fast electrical block to polyspermy are unfounded. Under laboratory conditions the majority of spermatozoa, although motile and capable of attaching to the oocyte surface, are either physiologically incompetent or attach to areas of the oocyte surface that do not support entry. © 2010 Springer Science+Business Media, LLC. Source

Menezo Y.,London Fertility Associates | Menezo Y.,Laboratoire Clement | Evenson D.,South Dakota State University | Cohen M.,Procrelys | And 2 more authors.
Advances in Experimental Medicine and Biology

According to worldwide statistics, between one in four and one in five couples have fertility problems. These problems are equally distributed between males and females. Modern lifestyle has obviously increased these problems: endocrine-disrupting chemicals, such as plastic polymer catalysts, alkylphenols, phthalates and so on, and cosmetic additives seem to be strongly involved in this fertility problem. Many of these compounds increase oxidative stress (OS) and thus impair spermatogenesis. The oocyte has only a finite capacity, decreasing with maternal age, to repair sperm-borne decays. To decrease this DNA repair burden, reducing the sperm DNA damages linked to OS is tempting. Antioxidant vitamins are often given haphazardly; they are not very efficient and potentially detrimental. A detailed analysis of the sperm nucleus is mandatory (DNA fragmentation or lack of nuclear condensation) prior to any treatment. Here we discuss new concepts in OS and the corresponding therapeutic approaches. © 2014 Springer Science+Business Media New York. Source

Menezo Y.,Laboratoire dEylau | Dale B.,Center for Assisted Fertilization | Cohen M.,Clinique Natecia

The genome of all cells is protected at all times by mechanisms collectively known as DNA repair activity (DRA). Such activity is particularly important at the beginning of human life, i.e. at fertilization, immediately after and at the very onset of embryonic development. DRA in early development is, by definition, of maternal origin: the transcripts stored during maturation, need to control the integrity of chromatin, at least until the maternal/zygotic transition at the 4- to 8-cell stage in the human embryo. Tolerance towards DNA damage must be low during this critical stage of development. The majority of DNA damage is due to either apoptosis or reactive oxygen species (ROS). Apoptosis, abortive or not, is a common feature in human sperm, especially in oligoasthenospermic patients and FAS ligand has been reported on the surface of human spermatozoa. The susceptibility of human sperm to DNA damage is well documented, particularly the negative effect of ROS (Kodama et al., 1997; Lopes et al., 1998a, b) and DNA modifying agents (Zenzes et al., 1999; Badouard et al., 2007). DNA damage in sperm is one of the major causes of male infertility and is of much concern in relation to the paternal transmission of mutations and cancer (Zenzes, 2000; Aitken et al., 2003; Fernández-Gonzalez, 2008). It is now clear that DNA damaged spermatozoa are able to reach the fertilization site in vivo (Zenzes et al., 1999), fertilize oocytes and generate early embryos both in vivo and in vitro. The effect of ROS on human oocytes is not as easy to study or quantify. It is a common consensus that the maternal genome is relatively well protected while in the maturing follicle; however damage may occur during the long quiescent period before meiotic re-activation (Zenzes et al., 1998). In fact, during the final stages of follicular growth, the oocyte may be susceptible to damage by ROS. With regards to the embryo there is active protection against ROS in the surrounding environment i.e. in follicular and tubal fluid (El Mouatassim et al., 2000; Guerin et al., 2001). DNA repair activity in the zygote is mandatory in order to avoid mutation in the germ line (Derijck et al., 2008). In this review we focus on the expression of mRNAs that regulate DNA repair capacity in the human oocyte and the mechanisms that protect the embryo against de novo damage. © 2010 Cambridge University Press. Source

Dale B.,Center for Assisted Fertilization
Biochemical and Biophysical Research Communications

This purpose of this review is to look at the experimental evidence, both kinetic and electrophysiological, that led to the hypothesis of a fast electrical block to polyspermy in sea urchin eggs. The idea of a fast partial block, forwarded in the 1950's, that would reduce the receptivity of the egg surface by 1/20th following its interaction with the fertilizing spermatozoon, was based on experiments that treated fertilization as a first order chemical reaction. Here, I outline the criticisms of the Rothschild theory and demonstrate that the hypothesis of a fast partial block to polyspermy is unfounded. Notwithstanding, it was suggested in the 1970's that the membrane depolarization, induced by the fertilizing spermatozoon, prevented the interaction of supernumerary spermatozoa, the fast electrical block to polyspermy. While trans-membrane voltage recording has permitted a better understanding of the sequence of events occurring at fertilization, there is no evidence that depolarization prevents the interaction of supernumerary spermatozoa. Sperm entry is prevented at positive and negative potentials, in the voltage clamp configuration, however this is an artifact caused by the currents injected into the egg employed to hold the voltage constant in a non-physiological range. At permissive voltages, around -20 mV, where the current required to hold the voltage is minimal, only one spermatozoon normally enters the egg. Thus, irrespective of the egg voltage, the fertilizing spermatozoon is, in any case, attached to a privileged interaction site that permits entry and distinguishes it from supernumerary spermatozoa. Competence for monospermy is acquired during oocyte maturation and data on cortical organization in echinoderm eggs points to the actin filament system for regulating sperm entry. © 2014 Elsevier Inc. All rights reserved. Source

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