Spindles, mitochondria and redox potential in ageing oocytes

Studies of human oocytes obtained from women of advanced reproductive age revealed that spindles are frequently aberrant, with chromosomes sometimes failing to align properly at the equator during meiosis I and II. Chromosomal analyses of donated and spare human oocytes and cytogenetic and molecular studies on the origin of trisomies collectively suggest that errors in chromosome segregation during oogenesis increase with advancing maternal age and as the menopause approaches. Disturbances in the fidelity of chromosome segregation, especially at anaphase I, leading to aneuploidy are prime causes of reduced developmental competence of embryos in assisted reproduction, as well as being responsible for the genesis of genetic disease. This review provides an overview of spindle formation and chromosome behaviour in mammalian oocytes. Evidence of a link between abnormal mitochondrial function in oocytes and somatic follicular cells, and finally disturbances in chromosome cohesion and segregation, and cell cycle control in aged mammalian oocytes, are also discussed.     

Determining proportions of human X and Y sperm with a recombinant deoxyribonucleic acid probe carrying a homologous sequence of sex chromosomes

A molecular sexing assay method for human sperm DNA has been described, which is particularly suitable for estimating proportions of X and Y sperm in a large number of sample points. The method should have general applicability for testing any mammalian sperm species, since it is based on probing the homologous DNA sequences that are known to be present probably in all mammalian sex chromosomes.     

The Greek Orthodox position on the ethics of assisted reproduction

In dealing with reproduction, the Church believes that every human being has a beginning but has no end; this is why conception constitutes an event of unique importance. The exact moment of the beginning of life is unknown to man, but the logic of sexual intercourse without reproduction and of reproduction without sexual intercourse must be seen with concern. Irrespective of the way it is conceived, the embryo has both a human beginning and a human perspective and in it, along with cellular multiplication, another process takes place, the beginning and development of its soul. Although modern technology has greatly contributed to health research, its irrational use threatens to desacralize man and to treat him as a machine. For this reason, all modern techniques of artificial fertilization have ethical and spiritual parameters that compel the Church to state Her reservations. The Church cannot recommend assisted reproduction as the solution to infertility; instead, She proposes a non-secularized perception on life that guarantees simplicity, peace, abstinence and mutual trust between spouses. She does not oppose resorting to medical help, but, at the same time, suggests that men and women render their life into the hands of God.     

Regulation of female fertility by the endocannabinoid system

The role of endocannabinoids in mammalian reproduction is an emerging concept. Cannabinoids have been always identified as being harmful drugs, because of their negative effects on female reproduction. The discovery of endocannabinoids, endogenous lipids that bind to cannabinoid receptors, and of their involvement in procreation permitted better understanding of the significance of cannabinoid/endocannabinoid signalling in fertilization, preimplantation embryo development, implantation and postimplantation embryonic growth. These studies have also opened new perspectives in clinical applications, pointing to endocannabinoid signalling as a new target for correcting infertility, and for improving reproductive health in humans. This review will present endocannabinoids, their target receptors and metabolic enzymes, and will discuss the involvement of these bioactive lipids in female mammalian reproduction.     

A secular perspective on 21st century ethics in human reproduction: why religious views and attitudes are becoming obsolete and possibly dangerous

The application of reproductive technologies to humans has brought about a radical change in traditional perspectives about sexuality and reproduction. In the past, the field was surrounded by an aura of mystery, which allowed religion to grasp the subject firmly. Now an explosion of knowledge, and a new capacity to control all aspects of human reproduction are beginning to modify attitudes, so that the arenas of sexuality and reproduction are apparently undergoing a process of rapid secularization. As a result, religious solutions to reproductive problems are becoming obsolete and possibly dangerous, since they no longer adequately fulfill the needs of humanity in our modern era.     

Oestrogen and progesterone action on endometrium: a translational approach to understanding endometrial receptivity

Embryo attachment and implantation is critical to successful reproduction of all eutherian mammals, including humans; a better understanding of these processes could lead to improved infertility treatments and novel contraceptive methods. Experience with assisted reproduction, especially oocyte donation cycles, has established that despite the diverse set of hormones produced by the ovary in a cycle-dependent fashion, the sequential actions of only two of them, oestrogen and progesterone, are sufficient to prepare a highly receptive endometrium in humans. Further investigation on the endometrial actions of these two hormones is currently providing significant insight into the implantation process in women, strongly suggesting that an abnormal response to progesterone underlies infertility in some patients.Embryo implantation is a key process in successful reproduction. A better understanding of the processes controlling implantation would lead to improved infertility treatments and new contraceptive methods. Experience with assisted reproduction, especially oocyte donation cycles, has established that, despite the variety of hormones produced by the ovary in a cyclic fashion, the sequential actions of only two of them, oestrogen and progesterone, are sufficient to prepare a human endometrium to be highly receptive to embryo implantation. Recent studies show that only a small amount of each of these hormones is necessary for most women. Further work strongly suggests that an abnormal response to progesterone underlies infertility in some patients.     

Assisted reproductive technologies and pregnancy outcomes: mechanistic insights from animal studies

Modern techniques in assisted reproduction have become a common and accepted form of clinical care benefiting an estimated 1 in 10 people of reproductive age who are subfertile or infertile. The success of these technologies relies, to large extent, on the remarkable tolerance of mammalian gametes and the preimplantation embryo to physical manipulations and alterations to their chemical environment. Recent reports from both human and animal studies, however, suggest that our faith in the ability of these "germ cells" to accurately recapitulate the normal process of early development under such conditions may be misplaced. While acknowledging the recognized risk factors of increased maternal age and infertility in human assisted reproductive technology (ART) subjects and the transfer of supernumerary embryos, evidence from animal studies indicates that ART procedures can directly contribute to the variable perinatal outcomes observed and imprinting disorders recently recognized. Controversy surrounds the specific nature and extent of these contributions; however, ovarian stimulation, in vitro maturation and embryo culture, intracytoplasmic sperm injection, and gamete/embryo cryopreservation have all been implicated. These issues are considered in detail in this article, which evaluates the insights that can be gained from studies with animals.     

Regulation of female fertility by the endocannabinoid system

Summary

The role of endocannabinoids in mammalian reproduction is an emerging concept. Cannabinoids have been always identified as being harmful drugs, because of their negative effects on female reproduction. The discovery of endocannabinoids, endogenous lipids that bind to cannabinoid receptors, and of their involvement in procreation permitted better understanding of the significance of cannabinoid/endocannabinoid signalling in fertilization, preimplantation embryo development, implantation and postimplantation embryonic growth. These studies have also opened new perspectives in clinical applications, pointing to endocannabinoid signalling as a new target for correcting infertility, and for improving reproductive health in humans. This review will present endocannabinoids, their target receptors and metabolic enzymes, and will discuss the involvement of these bioactive lipids in female mammalian reproduction.     

An integrated view of L-selectin and trophinin function in human embryo implantation

Determining molecular mechanisms of human embryo implantation is an extremely challenging task due to the limitation of materials and significant differences underlying this process among mammalian species. Recently, L-selectin and its ligand carbohydrate have been proposed as a system that mediates initial adhesion of human blastocysts to the uterine epithelia. We have also identified trophinin as a unique apical cell adhesion molecule potentially involved in the initial adhesion of trophectoderm of the human blastocyst to endometrial surface epithelia. In the mouse, the binding between ErbB4 on the blastocyst and heparin-binding epidermal growth factor-like growth factor on the endometrial surface enables the initial step of the blastocyst implantation. The evidence suggests that L-selectin and trophinin are included in human embryo implantation. This review summarizes findings relevant to the functions of L-selectin and trophinin in human embryo implantation, and proposes a model that reconciles these cell adhesion mechanisms.     

Simple gamete preservation and artificial reproduction of mammals using micro‐insemination techniques

Assisted reproductive technology (ART) has been applied in various procedures as an effective breeding method in experimental, domestic, and wild animals, and for the treatment of human infertility. Micro‐insemination techniques such as intracytoplasmic injection of spermatozoa and spermatids are now routinely used ART tools. With these techniques, even immotile and immature sperm cells can be employed as donors for producing the next generation. Gamete preservation, another ART tool, has contributed to reproductive regulation, worldwide transportation, and disease protection of animal strains, and the preserved gametes have been effectively used for the production of offspring. ART is now an indispensable tool in mammalian reproduction. This review covers the latest ART tools, with a particular emphasis on micro‐insemination and gamete preservation, and discusses the future direction of mammalian artificial reproductive technology.     

表皮生长因子家族与哺乳动物的胚胎着床

表皮生长因子家族是由表皮生长因子 (EGF)、转化生长因子 α(TGFα)、肝素结合性EGF样生长因子 (HB-EGF)、两性调节蛋白 (AR)、β-细胞调节素 (BTC)、epiregulin、NDFs(neu differentiation factors)等生长因子所构成 ,这些因子可与 EGF受体家族结合。EGF受体家族包括 Erb B1 (EGFR)、Erb B2 (HER2 )、Erb B3(HER3)和 Erb B4(HER4)四种受体酪氨酸激酶。这些生长因子与 EGF受体家族相互作用 ,在哺乳动物生殖过程中起重要的调节作用。本文对 EGF家族在哺乳动物胚胎着床过程中的作用进行了综述     

四跨膜蛋白超家族成员在胚胎植入中的作用

胚胎植入是哺乳动物生殖过程的关键环节.妊娠的正常建立和维持依赖囊胚与容受态子宫内膜间的相互作用,其中滋养细胞精确的侵入程度和子宫内膜的蜕膜化起重要作用.与肿瘤转移相似,滋养细胞侵袭子宫内膜也包括识别、黏附、侵袭、转移等过程,不同的是滋养细胞的侵袭行为具有＂自限性＂,是由一个复杂的网络系统精确调控的.四跨膜蛋白超家族成员以其在调控细胞黏附、侵袭、转移中独特的生物学作用,不仅在肿瘤转移中起重要作用,也在胚胎植入过程中扮演重要角色.     

Leptin system in embryo development and implantation: a protein in search of a function

Implantation is a crucial moment in the reproduction process that requires perfect synchronization between the embryo and the maternal endometrium. The embryo must reach the blastocyst stage and the endometrium must be prepared to receive it. An appropriate and specific molecular dialogue must also take place between them. There is ample evidence to show that the leptin system is implicated in this cross-talk. Examples are described. Although there is some controversy surrounding the data, they are supported by the presence of leptin receptor mRNA in mouse and human oocytes and embryos throughout preimplantation development. Otherwise, the leptin mRNA is only detected at the blastocyst stage in both human and mouse. Furthermore, leptin is found at higher concentrations in the conditioned media from competent human blastocysts than in those from arrested embryos, suggesting that this molecule is a marker for blastocyst viability. Given that expression of the leptin receptor increases in the human endometrium during the luteal phase, the secreted leptin could trigger its activation. Finally, leptin and the leptin receptor have been detected in implantation sites. All these findings point to the involvement of the leptin system in the molecular mechanism of the implantation process and embryo development.     

Recent molecular approaches to elucidate the mechanism of embryo implantation: trophinin, bystin, and tastin as molecules involved in the initial attachment of blastocysts to the uterus in humans

Elucidation of the implantation mechanism in humans at the molecular level has been difficult because of methodological restrictions. Instead of using human materials during the implantation period, two human tumor cell lines that respectively mimic the biological behaviors of a blastocyst and uterine luminal epithelial cells were utilized successfully to identify three novel adhesion molecules named trophinin, bystin, and tastin. Trophinin is a membrane protein strongly expressed both on the apical surface of the trophectoderm of a simian blastocyst and at a putative implantation site of the human endometrium. Bystin and tastin are cytoplasmic proteins that associate with trophinin by presumably forming an active adhesion machinery. The expression patterns of these molecules are suggestive of their involvement in the initial blastocyst attachment to the uterus as well as in the subsequent placental development. Future perspectives in molecular implantation research are also discussed in relation to breakthroughs in assisted reproduction.     

Preeclampsia and human reproduction. An essay of a long term reflection

Hypertensive disorders of pregnancy (HDP: pregnancy-induced hypertension, preeclampsia, eclampsia) affect approximately 10% of human births. Women are at increased risk for HDP during their first conception; and/or when the conception is with a new partner (new paternity); when conception occurs very shortly after the beginning of their sexual relationship. A primary cause of preeclampsia is the defect of the normal human-specific deep endovascular invasion of trophoblast, which is a consequence of the nutritional demands of growth of the human fetal brain. The occurrence of preeclampsia represents a reproductive disadvantage unique to humans compared with other mammals. As such, it may have played a significant role in shaping human reproduction and, therefore, human sexuality. This deep implantation/preeclampsia phenomenon may explain many anthropological mysteries of human sexuality that do not exist in other mammalian species (and primates). These include: very low fertility rate, concealed ovulation, all year long 'apparent-waste-of-efficiency' sexuality, absence of sperm competition in human females at the time of conception, and the unexplained testicle size in human males compared with relevant primates. Further, this deep trophoblastic implantation (and its failure in preeclampsia) in humans might be a decisive condition of hominization between great apes and all the other Homo genuses. This frontier might even have occurred inside these Homo lineages: because of their relatively small brains, the first species of Homo might not have presented the deep trophoblastic invasion described in Homo sapiens.     

Proteomics in reproductive medicine: the technology for separation and identification of proteins

With the near completion of the human genome project, reproductive biology is poised to enter the vastly more complex arena of proteomics. Proteomics involves the identification, characterization and quantitation of all proteins present in a cell at a particular metabolic state. Although the number of genes in the human genome is estimated to be about 27,000 +/- 5000, the number of proteins produced by humans is unknown, with estimates ranging as high as 1,500,000 distinct molecular entities. In order to address problems in the early stages of reproduction, proteomics must be scaled down to work with very few numbers of cells, termed zeptoproteomics. Mass spectrometry has rapidly become the key technology in proteomics, enabling rapid and facile identification and quantitation of femtomole and attomole quantities of a protein.     

Reproduction in the space environment: Part I. Animal reproductive studies

Mankind's exploration and colonization of the frontier of space will ultimately depend on men's and women's ability to live, work, and reproduce in the space environment. This paper reviews animal studies, from microorganisms to mammals, done in space or under space-simulated conditions, which identify some of the key areas which might interfere with human reproductive physiology and/or embryonic development. Those space environmental factors which impacted almost all species included: microgravity, artificial gravity, radiation, and closed life support systems. These factors may act independently and in combination to produce their effects. To date, there have been no studies which have looked at the entire process of reproduction in any animal species. This type of investigation will be critical in understanding and preventing the problems which will affect human reproduction. Part II will discuss these problems directly as they relate to human physiology.     

Characteristics and control of the normal menstrual cycle

The most important activity during the follicular phase of the cycle is the secretion of gonadotropins, which control folliculogenesis and influence uterine proliferation. The dominant events of the periovulatory phase are the LH surge and ovulation. The significant change during the luteal phase is the production of a nutritive mucus by the endometrial glands in preparation for an embryonic blastocyst. The cardinal passage of the menstrual phase is the menstrual flow itself. These different events (and the metabolic processes that regulate them) have wide-ranging effects on the integrity of the body. As Havelock Ellis, the eminent English psychologist, stated at the turn of this century, "the omnipresent process of sex, as it is woven into the whole texture of our body, is the pattern of all the process of our life" (source unknown). The sweeping influences of the menstrual cycle illustrate the extent to which the process of reproduction is indeed woven into the whole of the human body.     

The decision-making role of fathers in assisted reproduction

In order to bring about a pregnancy using assisted human reproduction, all current techniques require male and female gametes, except reproductive cloning, which has not yet been achieved and is illegal in many countries. This is, however, not the same as saying that bringing about such a pregnancy requires a husband and a wife, a commissioning couple, or a man and a woman: or to say that there is a father involved in the process in more than the narrowest biological sense. In this paper, I discuss the role of the man in assisted reproduction. I initially look at the role of the man in assisted insemination by donor and then, for the main part of the paper, analyse the role of the man in the various phases of decision-making in a male–female couple who seek assisted human reproduction. I first argue that there is justification for giving men a larger decision-making role in preimplantation decision making than they are often given, and then argue that since decisions concerning frozen gametes and embryos fall into this category, men are justified in preventing their partners from using frozen embryos after a breakdown in the relationship. Throughout the analysis, I consider various counter arguments and although the analysis is primarily philosophical, it will also discuss some pertinent legal decisions.