Reviews of reproduction最新文献

Heterotrimeric G proteins are actively involved in intracellular signalling in the myometrium and play important roles in regulating myometrial contraction and relaxation. Increases in intracellular calcium can be induced by agents that stimulate uterine contractions. In a number of instances, these increases in intracellular calcium are attributed to stimulation of phospholipase C by either G alpha or G betagamma subunits as a result of activation of G protein-coupled plasma membrane receptors. This mechanism also stimulates calcium entry through calcium release-activated channels, either directly or indirectly. Thus, while phospholipase C can be activated by other pathways and calcium can enter myometrial cells through other channels, G proteins play a major role in these processes. Similarly, activation of protein kinase A and protein kinase C are consequences of G protein activation. Protein kinase A and protein kinase C exert a number of regulatory influences on phospholipase C, ion channel activity and other processes in the myometrium. The mitogen-activated protein kinase pathway can also be activated directly or indirectly by the action of G proteins in myometrium. Responsiveness to G proteins can be altered during pregnancy and depends on the relative expression of all of the components of the signalling pathways involved. The balance between G protein-mediated stimulatory and inhibitory signalling pathways has important consequences for the control of myometrial contractile activity.

Ovarian failure leading to infertility can be caused by improper prenatal development of the fetal gonad or disruption of the complex postnatal process of folliculogenesis due to alterations in intragonadal or extragonadal regulation. It is critical to have physiological models that mimic events occurring during human development to understand, treat, and prevent ovarian failure in women. Many workers have chosen the mouse as the mammalian model with which to study ovarian function. This review summarizes several key events in female gonadogenesis and folliculogenesis in mice with specific emphasis on spontaneous or induced mutations yielding mouse models that have female infertility owing to ovarian failure.

Male sex steroids (androgens) are important for maintaining sperm production and growth of the accessory sex organ, the prostate gland. This article examines the role of the androgen receptor (AR) in the control of spermatogenesis and focusses on the N-terminal transactivation domain of the receptor, a poorly studied region that is essential for receptor function. This domain is of great interest because of its causative relationship to a fatal neuromuscular disease, spinal bulbar muscular atrophy (Kennedy's syndrome). Genetic screening of the transactivation domain of the AR gene of 153 patients presenting solely with defective spermatogenesis and male infertility, and of over 72 healthy fertile controls was performed. Up to 20% of infertile males have reduced androgenicity caused by an increase in length of a polymorphic trinucleotide (CAG) repeat segment, encoding a polyglutamine tract, of the androgen receptor. The increased risk of male infertility associated with long CAG lengths is associated with reduced risk of prostate cancer. Conversely, short polyglutamine tracts are associated with increased risk of prostate cancer but a reduced risk of male infertility. Thus depressed spermatogenesis and prostate cancer represent opposite ends of the spectrum of androgen receptor transactivation function. Improved understanding of androgen receptor action in these two important public health concerns could lead to rational and effective prevention and therapy.

The extraretinal photoreceptors of non-mammalian vertebrates play an important role in the regulation of temporal physiology. Both the regulation of circadian clocks and the photoperiodic response of many animals depend upon the photic information provided by these receptors. Since their discovery at the beginning of this century, and despite their importance, extraretinal photoreceptors have remained poorly understood. Until recently, their cellular location within the central nervous system, and the nature of the photopigments they use, remained a mystery. Antibodies directed against rod or cone photopigment proteins have been used in immunocytochemical procedures to localize extraretinal photoreceptors. However, findings have been confusing. The use of molecular approaches has led to the identification of several new photopigment gene families. Significantly, these genes are not expressed in the rods and cones of the retina, but in many sites within the central nervous system. Moreover, molecular approaches have proved useful in clarifying some of the earlier immunocytochemical results. Collectively, the recent findings show that non-mammalian vertebrates possess multiple extraocular photoreceptors that may express novel, rod or even cone photopigments. The future challenge is to link these photoreceptors with circadian and photoperiodic physiology.

Bovine and ovine embryos exposed to a variety of unusual environments prior to the blastocyst stage have resulted in the development of unusually large offspring which can also exhibit a number of organ defects. In these animals, the increased incidence of difficult parturition and of fetal and neonatal losses has limited the large-scale use of in vitro embryo production technologies commonly used in humans and other species. Four different situations have been identified that result in the syndrome: in vitro embryo culture, asynchronous embryo transfer into an advanced uterine environment, nuclear transfer and maternal exposure to excessively high urea diets. However, programming of the syndrome by all of these situations is unpredictable and not all of the symptoms described have been observed universally. Neither the environmental factors inducing the large offspring syndrome nor the mechanisms of perturbation occurring in the early embryo and manifesting themselves in the fetus have been identified.

Steroid action is mediated by specific intracellular receptors, which are shifted to a transcriptionally active state after ligand binding. In 1996, the cloning of a new member of the nuclear receptor superfamily from the rat prostate was reported. Ligand-binding experiments have shown that this receptor binds specifically to oestrogens and it has been named oestrogen receptor beta (ER beta) to distinguish it from the oestrogen receptor (ER alpha) cloned from uterus in 1986. The alpha and beta forms of the oestrogen receptor have identical numbers of exons, and the cDNAs cloned from humans, rats and mice all share significant sequence homologies especially within their DNA and ligand-binding domains. Splice variants of ER beta have been identified. ER beta mRNA and protein have been detected in a wide range of tissues including the vasculature, bone, brain, heart and the gonads and genital tracts in both males and females, and in some, but not all, tissues the pattern of expression is distinct from that of ER alpha. Studies in vitro have demonstrated that ER alpha and ER beta can exist as hetero- or homodimers and that these forms may interact differentially with response elements on genes. The identification of ER beta has made us rethink the potential sites of action of both endogenous oestrogens and exogenous natural and synthetic oestrogens and anti-oestrogens and is currently the subject of intensive research efforts.

Mitochondrial DNA (mtDNA) forms a semi-autonomous asexually reproducing genome in eukaryotic organisms. It plays an essential role in the life cycle through the control of energy production, by the inherently dangerous process of oxidative phosphorylation. The asymmetric nature of its inheritance--almost exclusively through the female--imposes different evolutionary constraints on males and females, and may lie at the heart of anisogamy. This review examines the implications of recent findings on the biology of mtDNA for reproduction and inheritance in mammals.

For the mother, lactation represents the final stage of an investment in her genetic material. Like any investment it is costly and, hence, it needs to be carefully controlled. To her offspring, lactation means survival, so it must happen at any cost. This apparent conflict is rationalized by the mother devolving some control to the offspring while retaining ultimate sanction herself. Part of this results from overt and more subtle influences of the presence of young on the mother's endocrine system, but an equally important part operates at each mammary gland to ensure that output is appropriate to the needs of the young, and no more. The young exert influence by removing milk, while the mother retains control by responding on an hour to hour basis to the presence of milk in the gland. Local control is inevitably most evident where secretion itself is concerned, but also operates to influence lactogenesis, gland development and, eventually, gland involution. This paper will review local control of mammary function, emphasising the important role played by an autocrine inhibitory protein, the feedback inhibitor of lactation.

By using various methods, ranging from conventional protein separation and purification to monoclonal antibody and cDNA cloning strategies, a considerable body of information has been obtained on mammalian epididymal proteins. Molecular characterization of proteins specifically produced in the human epididymis has been achieved by cDNA cloning, followed by raising antibodies against synthetic peptide epitopes. The predicted proteins have been localized in the human epididymal epithelium, within the lumen of the epididymal duct and vas deferens, and also on the surface of ejaculated spermatozoa. Sperm association has been reported for at least four human epididymal proteins, ARP, HE2, HE4, and HE5/CD52. However, as is largely the case in other species, a link to a specific function for any luminal component of the human epididymis, including the cloned secretory glycoproteins, to either sperm maturation or storage has not yet been demonstrated convincingly. Indirect evidence for a function for epididymal proteins comes from their relatively high frequency and tissue-specific expression as well as from their distinct spatial expression patterns along the human epididymal duct. However, it remains to be established (for example, by using the proteins and their antibodies in functional tests) whether, besides being essential markers of sperm maturation, they are also functionally important.