Zoology - Research Publications

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    Placental expression of pituitary hormones is an ancestral feature of therian mammals
    Menzies, BR ; Pask, AJ ; Renfree, MB (BMC, 2011)
    BACKGROUND: The placenta is essential for supplying nutrients and gases to the developing mammalian young before birth. While all mammals have a functional placenta, only in therian mammals (marsupials and eutherians) does the placenta closely appose or invade the uterine endometrium. The eutherian placenta secretes hormones that are structurally and functionally similar to pituitary growth hormone (GH), prolactin (PRL) and luteinizing hormone (LH). Marsupial and eutherian mammals diverged from a common ancestor approximately 125 to 148 million years ago and developed distinct reproductive strategies. As in eutherians, marsupials rely on a short-lived but functional placenta for embryogenesis. RESULTS: We characterized pituitary GH, GH-R, IGF-2, PRL and LHβ in a macropodid marsupial, the tammar wallaby, Macropus eugenii. These genes were expressed in the tammar placenta during the last third of gestation when most fetal growth occurs and active organogenesis is initiated. The mRNA of key growth genes GH, GH-R, IGF-2 and PRL were expressed during late pregnancy. We found significant up-regulation of GH, GH-R and IGF-2 after the start of the rapid growth phase of organogenesis which suggests that the placental growth hormones regulate the rapid phase of fetal growth. CONCLUSIONS: This is the first demonstration of the existence of pituitary hormones in the marsupial placenta. Placental expression of these pituitary hormones has clearly been conserved in marsupials as in eutherian mammals, suggesting an ancestral origin of the evolution of placental expression and a critical function of these hormones in growth and development of all therian mammals.
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    A Guide to the care and use of Australian native mammals in research and teaching (2014). National Health and Medical Research Council
    National Health and Medical Research Council, ; Handasyde, K ; Holz, P ; Kelly, D ; Renfree, MB ; Webb, C ; National Health and Medical Research Council, ; Handasyde, K ; Holz, P ; Kelly, D ; Renfree, MB ; Webb, C (National Health and Medical Research Council, 2014)
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    Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development
    Renfree, MB ; Papenfuss, AT ; Deakin, JE ; Lindsay, J ; Heider, T ; Belov, K ; Rens, W ; Waters, PD ; Pharo, EA ; Shaw, G ; Swwong, E ; Lefevre, CM ; Nicholas, KR ; Kuroki, Y ; Wakefield, MJ ; Zenger, KR ; Wang, C ; Ferguson-Smith, M ; Nicholas, FW ; Hickford, D ; Yu, H ; Short, KR ; Siddle, HV ; Frankenberg, SR ; Chew, KY ; Menzies, BR ; Stringer, JM ; Suzuki, S ; Hore, TA ; Delbridge, ML ; Mohammadi, A ; Schneider, NY ; Hu, Y ; O'Hara, W ; Al Nadaf, S ; Wu, C ; Feng, Z-P ; Cocks, BG ; Wang, J ; Flicek, P ; Searle, SMJ ; Fairley, S ; Beal, K ; Herrero, J ; Carone, DM ; Suzuki, Y ; Sugano, S ; Toyoda, A ; Sakaki, Y ; Kondo, S ; Nishida, Y ; Tatsumoto, S ; Mandiou, I ; Hsu, A ; McColl, KA ; Lansdell, B ; Weinstock, G ; Kuczek, E ; McGrath, A ; Wilson, P ; Men, A ; Hazar-Rethinam, M ; Hall, A ; Davis, J ; Wood, D ; Williams, S ; Sundaravadanam, Y ; Muzny, DM ; Jhangiani, SN ; Lewis, LR ; Morgan, MB ; Okwuonu, GO ; Ruiz, SJ ; Santibanez, J ; Nazareth, L ; Cree, A ; Fowler, G ; Kovar, CL ; Dinh, HH ; Joshi, V ; Jing, C ; Lara, F ; Thornton, R ; Chen, L ; Deng, J ; Liu, Y ; Shen, JY ; Song, X-Z ; Edson, J ; Troon, C ; Thomas, D ; Stephens, A ; Yapa, L ; Levchenko, T ; Gibbs, RA ; Cooper, DW ; Speed, TP ; Fujiyama, A ; Graves, JAM ; O'Neill, RJ ; Pask, AJ ; Forrest, SM ; Worley, KC (BMC, 2011)
    BACKGROUND: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. RESULTS: The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. CONCLUSIONS: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution.
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    Rsx is a metatherian RNA with Xist-like properties in X-chromosome inactivation
    Grant, J ; Mahadevaiah, SK ; Khil, P ; Sangrithi, MN ; Royo, H ; Duckworth, J ; McCarrey, JR ; VandeBerg, JL ; Renfree, MB ; Taylor, W ; Elgar, G ; Camerini-Otero, RD ; Gilchrist, MJ ; Turner, JMA (NATURE PUBLISHING GROUP, 2012-07-12)
    In female (XX) mammals, one of the two X chromosomes is inactivated to ensure an equal dose of X-linked genes with males (XY). X-chromosome inactivation in eutherian mammals is mediated by the non-coding RNA Xist. Xist is not found in metatherians (marsupials), and how X-chromosome inactivation is initiated in these mammals has been the subject of speculation for decades. Using the marsupial Monodelphis domestica, here we identify Rsx (RNA-on-the-silent X), an RNA that has properties consistent with a role in X-chromosome inactivation. Rsx is a large, repeat-rich RNA that is expressed only in females and is transcribed from, and coats, the inactive X chromosome. In female germ cells, in which both X chromosomes are active, Rsx is silenced, linking Rsx expression to X-chromosome inactivation and reactivation. Integration of an Rsx transgene on an autosome in mouse embryonic stem cells leads to gene silencing in cis. Our findings permit comparative studies of X-chromosome inactivation in mammals and pose questions about the mechanisms by which X-chromosome inactivation is achieved in eutherians.
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    Parturition and perfect prematurity: birth in marsupials
    Shaw, G ; Renfree, MB (CSIRO PUBLISHING, 2006)
    Marsupials are distinguished from eutherian mammals in their mode of reproduction. They give birth to a highly altricial young, which completes its development whilst attached to a teat, usually within a pouch. The marsupial neonate has relatively well-developed digestive, respiratory and circulatory systems but retains its fetal excretory system with a fully functional mesonephric kidney and undifferentiated gonads and genitalia. We have investigated birth in the tammar wallaby (Macropus eugenii) and shown that the tiny (400 mg) fetus determines the time of its own delivery. Although plasma progesterone falls, and oestradiol associated with the postpartum oestrus typically rises, around the time of parturition, neither hormone is essential for the timing of birth. However relaxin may loosen the connective tissue of the cervix and vaginae for birth. Labour starts suddenly and is completed within minutes. Both prostaglandins and mesotocin are essential for the contractions that deliver the young. Prostaglandins from the reproductive tract act via the brain to control parturient behaviour. In the last 2 days of gestation fetal adrenal glucocorticoid production increases, promoting lung maturation and surfactant production and ultimately triggering labour. The accessibility of the altricial neonatal marsupial provides a unique opportunity for experimental manipulation of organ development and maturation.
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    The functional development of Leydig cells in a marsupial
    Butler, CM ; Shaw, G ; Clark, J ; Renfree, MB (WILEY, 2008-01)
    Leydig cells are the major source of androgen in the male mammal. We describe here for the first time the development of the Leydig cell in a macropodid marsupial, the tammar wallaby, Macropus eugenii. Leydig cells are first recognized morphologically 2 days after birth with the appearance of lipid droplets in the cytoplasm of certain interstitial cells. Lipid content closely matches the steroid content of the developing testis and marks the maturation of the steroid synthesis pathway in the tammar testis. Morphologically mature Leydig cells, marked by distinct mitochondria with tubular cristae and an extensive anastomosing network of smooth endoplasmic reticulum, are developed by day 10 after birth - the time of peak testosterone content in perinatal tammar testes. The volume percentage of each cell type in the testis does not change over time so the growth of each cellular component keeps pace with growth of the whole testis. There was no morphological or quantitative evidence of a change from one population of Leydig cells to another in the tammar testis as has been reported in several other species including the rat, mouse and human. Maturation of the testis is also marked by the development of tight junctions between the cell membranes of adjacent Sertoli cells. These appear around day 30 after birth and coincide with the onset of mitotic arrest in male germ cells. Overall, the development of the Leydig cell in the tammar wallaby follows a similar pattern to that seen in other mammals, although the start of Leydig cell differentiation is, like many other organ systems in marsupials, post natal, not fetal and there appears to be only a single population of Leydig cells.
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    Ultrasonography of wallaby prenatal development shows that the climb to the pouch begins in utero
    Drews, B ; Roellig, K ; Menzies, BR ; Shaw, G ; Buentjen, I ; Herbert, CA ; Hildebrandt, TB ; Renfree, MB (NATURE PUBLISHING GROUP, 2013-03-15)
    Marsupials have a functional placenta for a shorter period of time compared to that of eutherian species, and their altricial young reach the teats without any help from the mother. We have monitored the short intrauterine development of one marsupial, the tammar wallaby, with high-resolution ultrasound from reactivation of the 100-cell diapausing blastocyst to birth. The expanding blastocyst could be visualized when it had reached a diameter of 1.5 mm. From at least halfway through pregnancy, there are strong undulating movements of the endometrium that massage the expanding vesicle against the highly secretory endometrial surface. These unique movements possibly enhance exchange of uterine secretions and gases between the mother and embryo. There was a constant rate of development measured ultrasonographically from mid-gestation, regardless of when the blastocyst reactivated. Interestingly climbing movements by the fetus began in utero about 3 days before birth, mimicking those required to climb to the pouch.