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Mitochondria as elements of developmental competence and regulation in the oocyte and preimplantation-stage embryo
Abstracts - WARM: Beyond infertility: breakthroughs in reproductive medicine and technology
Gender-based medicine – the coming revolution in medical perception Glezerman M Rabin Medical Center, Hospital for Women, Petah Tikva and Sackler Medical School, Tel Aviv University, Israel Gender may be defined as the social, environmental and anthropological self-conception of an individual as being male or female, as distinguished from the actual biological sex. The different roles to which the two genders have been assigned throughout the development of mankind have lead to fundamental differences in bodily systems far beyond the differences in the genital organs. It is therefore surprising that most diseases have been studied in men only and most drugs to treat men and women alike have been assessed in men only. Following the diethylstilbestrol disaster in the 1950s and the thalidomide catastrophe in the 1960s, during which many infants with severe malformations were born following medical treatment of their pregnant mothers, this apparent discrimination was applied with good intention, namely to avoid inadvertent inclusion of pregnant women into clinical studies. The end results, however, remain the same: an almost universal neglect of the physiological and pathophysiological differences in virtually all bodily systems between men and women. This presentation will address these issues and is aimed to raise awareness as to the ongoing emerging new science of gender-based medicine. Mitochondria as elements of developmental competence and regulation in the oocyte and preimplantation-stage embryo Van Blerkom J Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado, 80309; Colorado Reproductive Endocrinology, Rose Medical Center, Denver, Colorado, 80220 Studies of mitochondria in early development have been largely concerned with their metabolic contribution to the bioenergetic status of the oocyte and preimplantation stage embryo, i.e., the relationship between levels of ATP production and competence. This presentation will review the current understanding of: (i) different mitochondrial functions and activities that contribute to competence for the oocyte and early embryo; (ii) whether a developmentally significant correspondence exists between mitochondrial DNA (mt DNA) copy number and complement size; and (iii) how differences in their spatial organization within the oocyte and patterns of inheritance between blastomeres are important determinants of developmental competence for the embryo. Evidence to be presented supports the notion that mitochondrial function extends beyond a metabolic contribution and includes participation in the focal regulation of calcium homeostasis, signal transduction and modifications of complex lipids associated with the oolemma that may be a prerequisite for fertilization. Current findings indicate that a spatially distinct domain of differential mitochondrial polarity (transmembrane potential) occurs and may be regulatory with respect to levels of these activities in the oocyte and early embryo. Mitochondrial activity appears to be tightly regulated in the oocyte and the newly fertilized egg by a combination of intrinsic influences (e.g., concentrations of free calcium and certain amino acids) and extrinsic influences (e.g., cumulus–
S-2 Reproductive BioMedicine Online, Vol. 17, Suppl. 2, September 2008
oophorus-derived nitric oxide), and it is suggested that such regulation is critical to the establishment of competence. These findings provide new insights into the pleiotropic nature of mitochondrial function in early development, how activity may be locally and differentially regulated within the cytoplasm, and the extent to which oocyte-specific differences in complement size, distribution and activity are important determinants of developmental normality. Fertility preservation Revel A Hadassah University Hospital, Jerusalem, Israel Young survivors of cancer treatment are a growing population. This is mainly due the major advances in diagnosis and treatment of various malignant diseases common in young women and men. Fertility specialists ought to keep up with advancements in fertility preservation so as to be able to offer the most appropriate methods that will enable future fertility. Young patients facing potentially gonadotoxic chemotherapy are usually very interested in their fertility prognosis and potential. Awareness of a patient’s needs and aspirations is crucial at an early phase of consultation so as not to miss opportunities to intervene before chemotherapy. Close collaboration and approval by adult or paediatric haematooncologists needs to be obtained prior to decision making. As the effect of chemotherapy on future fertility is mainly in postponing pregnancy in women, it is the age of the patient that becomes her adversary. Thus, the age of the female patient is the most important factor in consultation about her future pregnancy. Nevertheless, fertility is raised as an issue by a large range of ages from parents to young girls and boys and through to the fifth decade of life. Clearly the best approach is to prevent damage. Choosing less gonadotoxic treatment protocols is now possible for some diseases without reducing success. Surprisingly it has been found that patients are so concerned about the damage to their fertility that they may sometimes ask for less gonadotoxic treatment, even at the price of reducing 5-year survival rates. The use of gonadotrophin-releasing hormone analogues during chemotherapy can somewhat protect against damage, though prospective, randomized studies are needed. The availability of specific anti-apoptotic gonad-protecting medications is expected for humans in the future. The proven method of fertility preservation is slow freezing of embryos and spermatozoa for women and men respectively. Recently, vitrification of unfertilized oocytes offers a realistic pregnancy rate in single women. Prepubertal girls and boys are offered cryopreservation of gonadal tissue when the risk to future fertility is significant. Frozen ovarian cortex has enabled a small number of pregnancies, whereas no pregnancy has been obtained from human spermatogonial stem cells found in frozen–thawed testicular tissue. It is crucial to develop a multidisciplinary approach especially when dealing with children. The role of the fertility specialist continues throughout cancer treatment and has to deal with premature ovarian failure and early menopausal symptoms. Medical attention to hot flushes, vaginal atrophy and to osteoporosis is required. After cancer treatment, the ovarian reserve can be assessed by modern markers of the primordial follicles, such as the anti-mullerian hormone (AMH), and by sonographic counting of antral follicles. In patients wishing for pregnancy without available gametes, the use of donor eggs
Gender-based medicine – the coming revolution in medical perception Glezerman M Rabin Medical Center, Hospital for Women, Petah Tikva and Sackler Medical School, Tel Aviv University, Israel Gender may be defined as the social, environmental and anthropological self-conception of an individual as being male or female, as distinguished from the actual biological sex. The different roles to which the two genders have been assigned throughout the development of mankind have lead to fundamental differences in bodily systems far beyond the differences in the genital organs. It is therefore surprising that most diseases have been studied in men only and most drugs to treat men and women alike have been assessed in men only. Following the diethylstilbestrol disaster in the 1950s and the thalidomide catastrophe in the 1960s, during which many infants with severe malformations were born following medical treatment of their pregnant mothers, this apparent discrimination was applied with good intention, namely to avoid inadvertent inclusion of pregnant women into clinical studies. The end results, however, remain the same: an almost universal neglect of the physiological and pathophysiological differences in virtually all bodily systems between men and women. This presentation will address these issues and is aimed to raise awareness as to the ongoing emerging new science of gender-based medicine. Mitochondria as elements of developmental competence and regulation in the oocyte and preimplantation-stage embryo Van Blerkom J Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado, 80309; Colorado Reproductive Endocrinology, Rose Medical Center, Denver, Colorado, 80220 Studies of mitochondria in early development have been largely concerned with their metabolic contribution to the bioenergetic status of the oocyte and preimplantation stage embryo, i.e., the relationship between levels of ATP production and competence. This presentation will review the current understanding of: (i) different mitochondrial functions and activities that contribute to competence for the oocyte and early embryo; (ii) whether a developmentally significant correspondence exists between mitochondrial DNA (mt DNA) copy number and complement size; and (iii) how differences in their spatial organization within the oocyte and patterns of inheritance between blastomeres are important determinants of developmental competence for the embryo. Evidence to be presented supports the notion that mitochondrial function extends beyond a metabolic contribution and includes participation in the focal regulation of calcium homeostasis, signal transduction and modifications of complex lipids associated with the oolemma that may be a prerequisite for fertilization. Current findings indicate that a spatially distinct domain of differential mitochondrial polarity (transmembrane potential) occurs and may be regulatory with respect to levels of these activities in the oocyte and early embryo. Mitochondrial activity appears to be tightly regulated in the oocyte and the newly fertilized egg by a combination of intrinsic influences (e.g., concentrations of free calcium and certain amino acids) and extrinsic influences (e.g., cumulus–
S-2 Reproductive BioMedicine Online, Vol. 17, Suppl. 2, September 2008
oophorus-derived nitric oxide), and it is suggested that such regulation is critical to the establishment of competence. These findings provide new insights into the pleiotropic nature of mitochondrial function in early development, how activity may be locally and differentially regulated within the cytoplasm, and the extent to which oocyte-specific differences in complement size, distribution and activity are important determinants of developmental normality. Fertility preservation Revel A Hadassah University Hospital, Jerusalem, Israel Young survivors of cancer treatment are a growing population. This is mainly due the major advances in diagnosis and treatment of various malignant diseases common in young women and men. Fertility specialists ought to keep up with advancements in fertility preservation so as to be able to offer the most appropriate methods that will enable future fertility. Young patients facing potentially gonadotoxic chemotherapy are usually very interested in their fertility prognosis and potential. Awareness of a patient’s needs and aspirations is crucial at an early phase of consultation so as not to miss opportunities to intervene before chemotherapy. Close collaboration and approval by adult or paediatric haematooncologists needs to be obtained prior to decision making. As the effect of chemotherapy on future fertility is mainly in postponing pregnancy in women, it is the age of the patient that becomes her adversary. Thus, the age of the female patient is the most important factor in consultation about her future pregnancy. Nevertheless, fertility is raised as an issue by a large range of ages from parents to young girls and boys and through to the fifth decade of life. Clearly the best approach is to prevent damage. Choosing less gonadotoxic treatment protocols is now possible for some diseases without reducing success. Surprisingly it has been found that patients are so concerned about the damage to their fertility that they may sometimes ask for less gonadotoxic treatment, even at the price of reducing 5-year survival rates. The use of gonadotrophin-releasing hormone analogues during chemotherapy can somewhat protect against damage, though prospective, randomized studies are needed. The availability of specific anti-apoptotic gonad-protecting medications is expected for humans in the future. The proven method of fertility preservation is slow freezing of embryos and spermatozoa for women and men respectively. Recently, vitrification of unfertilized oocytes offers a realistic pregnancy rate in single women. Prepubertal girls and boys are offered cryopreservation of gonadal tissue when the risk to future fertility is significant. Frozen ovarian cortex has enabled a small number of pregnancies, whereas no pregnancy has been obtained from human spermatogonial stem cells found in frozen–thawed testicular tissue. It is crucial to develop a multidisciplinary approach especially when dealing with children. The role of the fertility specialist continues throughout cancer treatment and has to deal with premature ovarian failure and early menopausal symptoms. Medical attention to hot flushes, vaginal atrophy and to osteoporosis is required. After cancer treatment, the ovarian reserve can be assessed by modern markers of the primordial follicles, such as the anti-mullerian hormone (AMH), and by sonographic counting of antral follicles. In patients wishing for pregnancy without available gametes, the use of donor eggs