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    ABSTRACT: This article reviews the remarkable life and major scientific achievements of the reproductive biologist M.C. Chang. His scholarly career progressed from university in Peking, via Edinburgh, Scotland, and Cambridge, England, to the newly founded Worcester Foundation for Experimental Biology in Massachusetts. At each stage, the hand of fate is noted as are the support and encouragement of key professors. Chang's own contributions on capacitation of spermatozoa, in vitro fertilisation of mammalian eggs, and transplantation of oocytes and embryos are all brought out, as is his essential input to the creation and development of a steroid contraceptive pill. He strongly encouraged young reproductive biologists who worked in his laboratory, and applauded the world-wide distinction of his student and associate, R. Yanagimachi, as a specialist in mammalian fertilisation. Finally, Chang's continued feelings towards his homeland are contrasted with the reality of his American life after 1945, itself a study in poignancy.
    Human Fertility 05/2013; 16(2). DOI:10.3109/14647273.2013.790093
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    ABSTRACT: Deep body temperature in mammals is generally but incorrectly regarded as uniform. Alterations of temperature in oviducts and preovulatory Graafian follicles may play a vital role in gamete maturation, fertilization and early embryonic development. At a molecular level, the conformation of regulatory proteins is susceptible to changes in temperature. Deviation from physiological temperature during IVF procedures could thereby exert a profound influence on patterns of gene expression as the embryonic genome unfolds during early cleavage stages and act to generate specific anomalies. Systematic studies are urgently required. The temperature of internal body organs in mammals such as rabbits and humans is widely regarded as uniform, but this is not correct. Temperatures in reproductive tissues such as ovaries and oviducts vary according to the stage of a menstrual or oestrous cycle. Such changes in temperature are thought to be critically involved in the maturation of eggs and spermatozoa and thus in events shortly before and after fertilization. Proteins in the cytoplasm and nuclei of eggs and very young embryos respond to small shifts in temperature by changing their three-dimensional shape. Conformational modifications in regulatory proteins in the nucleus would influence patterns of gene expression in developing embryos and may, when perturbed, alter the sexual phenotype of an individual. In the practical context of IVF, studies are needed of the influence of culturing gametes and embryos at different temperatures and ranges of temperature on the patterns of gene expression in preimplantation embryos.
    Reproductive biomedicine online 01/2012; 24(4):377-80. DOI:10.1016/j.rbmo.2011.12.007
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    ABSTRACT: After recalling male gonadal physiology in respect of tissue temperatures within the scrotal sac, and raising questions concerning abdominal testes, attention turned to mature Graafian follicles and ovarian stroma. Temperature gradients between such tissues were summarized for human, rabbit, pig, and cow, and generally fell in the range of 1.3-1.7 degrees C: follicles were always cooler than stroma. Measurements were made principally by means of a thermo-sensing camera at midventral laparotomy, but also using microelectrodes or thermistor probes sited in the follicular antrum of rabbits and pigs, respectively. When thermo-imaged under the fimbriated extremity of the Fallopian tube, mature pig follicles and stroma could still be distinguished. Such follicles cooled slightly more rapidly during the first 10 s of a 60-s recording interval, after which curves for the two tissues remained parallel. Arresting ovarian blood supply for 5 min had a negligible influence on the temperature differentials. Endoscopy in three models recorded mean differentials of 0.6 +/- 0.1 degrees C - 1.1 +/- 0.1 degrees C between follicles and stroma, but such follicles had not attained mature diameter. Temperature gradients were thought to be generated at least in part by endothermic reactions within mature follicles, reflecting hydration of large extracellular matrix molecules such as proteoglycans. A contribution to the cooling process from the products of leukocyte activity in the follicle wall and antrum could also be involved. Temperature gradients would be maintained locally by counter-current heat exchange mechanisms and, in this context, the microvasculature and lymphatic flow of individual follicles were found to be appropriate. Observations on the temperature of preovulatory follicles appear relevant to procedures of in vitro maturation and in vitro fertilization.
    Microscopy Research and Technique 06/2006; 69(6):501-7. DOI:10.1002/jemt.20308
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    ABSTRACT: After clarifying regions of the female tract wherein spermatozoa are stored and the egg is fertilised, proposals are made for a modified site of sperm deposition in cattle. A deep pre-ovulatory insemination into the ipsilateral horn of the uterus-the side of the ovulatory follicle-should improve establishment of viable spermatozoa in the caudal region of the oviduct isthmus, the so-called functional sperm reservoir. Suppressed motility within viscous secretions and binding of sperm heads to endosalpingeal microvilli are features of this phase of storage. Activation and release of such spermatozoa would be prompted by imminent ovulation and associated ovarian endocrine programming by both local and systemic routes. Potential advantages of deep insemination include: (1) raising the fertility of genetically valuable bulls whose non-return rates are sub-optimal; (2) reducing the number of spermatozoa in each insemination dose; (3) exploiting the limited numbers of sex-selected sperm cells (X- and Y-chromosome-bearing spermatozoa) available from flow cytometry; (4) breeding from valuable but oligospermic bulls. Putative disadvantages might include: (1) rectal palpation of the ovaries to identify the pre-ovulatory follicle; (2) damage to or even perforation of the uterine wall by the insemination device; (3) the risk of polyspermic fertilisation; (4) specific training in the technique for non-clinically qualified inseminators. Each of these reservations receives comment. In conclusion, a modified technique of insemination should be feasible under commercial conditions, could be coupled with new sperm technologies, and would give a boost to the artificial insemination industry.
    Animal Reproduction Science 01/2004; 79(3-4):157-70. DOI:10.1016/S0378-4320(03)00163-5
  • Zygote 09/2003; 11(3):237-43. DOI:10.1017/S0967199403002284
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    ABSTRACT: In terms of experimental studies of the process of fertilization in mammals, this essay attempts to give a balanced assessment of current interpretations and to raise questions of direct relevance to two fields of research. First, the nature of pre-ovulatory sperm-endosalpingeal binding is set in a physiological perspective, and examination of this dynamic process in vitro is shown to suffer from serious shortcomings. In particular, sperm-epithelial binding reactions demonstrated in cultures of endosalpingeal cells may represent only a portion of the binding reaction in vivo or, as revealed by sperm binding to the tracheal epithelium, could be largely non-specific. Second, concerning the subsequent phase of binding of a fertilizing spermatozoon to the zona pellucida, the nature of the initial contact arrest of the sperm head is evaluated, especially in the light of the highly uneven or 'pitted' surface of this outer coating of the oocyte. Bearing in mind the active phase of oviduct macromolecular secretion that continues after ovulation, the question is posed as to how functional sperm binding sites are preserved on the surface of the zona pellucida rather than masked by epithelial and cumulus cell secretions. Finally, it is recalled that initial sperm : egg ratios at the site of fertilization in the ampullary-isthmic region of the oviduct are close to unity in diverse species of mammal, such fertilizing spermatozoa being released from prominent reserves in the caudal isthmus shortly before the time of ovulation. On strictly quantitative grounds, therefore, the extent to which biochemical or molecular studies portray changes in the vanguard of fertilizing spermatozoa needs to be questioned. Such studies are more likely to be descriptive of overall changes in very large numbers of sperm cells at diverse stages of maturation.
    Reproduction in Domestic Animals 05/2003; 38(2):147-54.
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    ABSTRACT: This essay reviews four topical aspects of Fallopian tube physiology that bear on either successful fertilization or early development of the zygote. An initial focus is on glycoprotein secretions of the duct that accumulate as a viscous mucus in the caudal isthmus. Because this is the site of the pre-ovulatory sperm reservoir, an involvement of the secretions is considered in: preventing uterine and ampullary tubal fluids from entering the functional sperm reservoir; removing residual male secretions from the sperm surface; deflecting spermatozoa towards endosalpingeal organelles and reducing flagellar beat before ovulation. The subtle prompting of flagellar movement with impending ovulation is examined in terms of potential reactivation mechanisms, with overall control attributed to increasing secretion of progesterone. The site of full capacitation and the acrosome reaction in a fertilizing spermatozoon is then debated, with strong arguments pointing to completion of these processes in the specific fluids at the ampullary-isthmic junction. Finally, the synthetic activity of cumulus cells released at ovulation as a paracrine tissue in the Fallopian tube is highlighted with reference to steroid hormones, peptides and cytokines. Not only does the suspension of granulosa-derived cells influence the process of fertilization, but also it may amplify oocyte or embryonic signals to the endosalpinx and ipsilateral ovary.
    Reproduction in Domestic Animals 09/2002; 37(4):186-90. DOI:10.1046/j.1439-0531.2002.00376.x
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    ABSTRACT: The condition of tubal ectopic pregnancy is presented from diverse points of view, bringing out physiological explanations for its occurrence in primates and striking absence in other mammals. Part of the flexibility underlying ectopic pregnancy in humans stems from the absence of a uterine luteolytic mechanism, enabling early embryonic development in the Fallopian tube without compromising function of the corpus luteum. Attention is devoted to a potential overlap between the composition of tubal and uterine fluids, and to specific mixing between the two fluid compartments, expressed in an ability of the human oocyte or zygote to tolerate transplantation to the uterus. Perturbed tubal oocyte transport is seen as a contributory factor, not least as a sequel to episodes of infection and a modified endosalpinx, but the essay then reasons strongly for an involvement of endometriosis in the aetiology of tubal ectopic pregnancy. Proliferation of refluxed endometrial tissue arrested within the Fallopian tube could provide the epithelial characteristics of a uterine environment. Accordingly, an experimental model is proposed for tubal ectopic pregnancy in animals based upon transplants of endometrial tissue and the subsequent introduction of embryos into both the Fallopian tubes and uterus; the latter would suppress the luteolytic mechanism. Finally, advances are suggested based upon molecular scanning of human ectopic tissues and those derived from animal models. If molecular probes could be developed to detect either early tubal pregnancy or a propensity to this pathology, such advances would clearly have clinical relevance-not least in view of an enhanced incidence of tubal pregnancy arising after assisted reproduction technology.
    Human Reproduction 08/2002; 17(7):1688-91. DOI:10.1093/humrep/17.7.1688
  • Reproduction in Domestic Animals 09/2001; 36(3-4):217-22. DOI:10.1046/j.1439-0531.2001.00304.x
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    ABSTRACT: This paper is concerned with endosalpingeal specialisations that underlie stabilisation of unique secretions forming microenvironments within the Fallopian tube lumen, not least as they influence the final stages of sperm transport and maturation. In particular, a specific microenvironment at the ampullary-isthmic junction in the presence of the newly-shed oocyte(s), associated granulosa cells and their secretory products is thought to characterise the site of fertilisation. Attention is also drawn to the viscous glycoprotein in the caudal isthmus before ovulation: it isolates spermatozoa stored with suppressed motility from the metabolic stimulation caused by uterine or ampullary fluid. This viscous secretion strips male antigens from the sperm surface, facilitating their preovulatory binding reactions to organelles of the isthmus epithelium. Peri-ovulatory activation of discrete numbers of viable spermatozoa is regulated by follicular progesterone secretion, but seemingly involves local mobilisation of Ca2+ ions into bound gametes of appropriate membranous maturity. Motility and progression to the site of fertilisation may be further heightened by an influence of catecholamines diffusing from the myosalpinx; receptors for such molecules are present on the sperm surface. There is tight control of sperm activation and release close to the time of ovulation, generating initial sperm:egg ratios at the ampullar-isthmic junction of close to unity. However, with establishment of the block to polyspermy in newly activated eggs and lapse of time after ovulation, control of sperm progression soon relaxes. Indeed, 2-4 cell embryos may contain large numbers of accessory spermatozoa on or in the zona pellucida.
    Italian journal of anatomy and embryology = Archivio italiano di anatomia ed embriologia 02/2001; 106(2 Suppl 2):279-89.
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