Genomic imprinting, parent-of-origin-specific gene expression, is controlled by differential epigenetic status of the parental chromosomes. While DNA methylation and suppressive histone modifications established during gametogenesis... more
Genomic imprinting, parent-of-origin-specific gene expression, is controlled by differential epigenetic status of the parental chromosomes. While DNA methylation and suppressive histone modifications established during gametogenesis suppress imprinted genes on the inactive allele, how and when the expressed allele gains its active status is not clear. In this study, we asked whether the active histone-3 lysine-4 trimethylation (H3K4me3) marks remain at paternally expressed genes (PEGs) in sperm and embryos before and after fertilization using published data. Here we show that mouse sperm had the active H3K4me3 at more than half of known PEGs, and these genes were present even after fertilization. Using reciprocal cross data, we identified 13 new transient PEGs during zygotic genome activation. Next, we confirmed that the 12 out of the 13 new transient PEGs were associated with the paternal H3K4me3 in sperm. Nine out of the 12 genes were associated with the paternal H3K4me3 in zygote...
Research Interests:
Embryonic diapause – a period of embryonic suspension at the blastocyst stage – is a fascinating phenomenon that occurs in over 130 species of mammals, ranging from bears and badgers to mice and marsupials. It might even occur in humans.... more
Embryonic diapause – a period of embryonic suspension at the blastocyst stage – is a fascinating phenomenon that occurs in over 130 species of mammals, ranging from bears and badgers to mice and marsupials. It might even occur in humans. During diapause, there is minimal cell division and greatly reduced metabolism, and development is put on hold. Yet there are no ill effects for the pregnancy when it eventually continues. Multiple factors can induce diapause, including seasonal supplies of food, temperature, photoperiod and lactation. The successful reactivation and continuation of pregnancy then requires a viable embryo, a receptive uterus and effective molecular communication between the two. But how do the blastocysts survive and remain viable during this period of time, which can be up to a year in some cases? And what are the signals that bring it out of suspended animation? Here, we provide an overview of the process of diapause and address these questions, focussing on recen...
Research Interests:
Research Interests:
in semen quality and morphology of the reproductive tract of the male tammar wallaby parallel seasonal breeding activity in the female
Male germ cells undergo two consecutive processes - pre-spermatogenesis and spermatogenesis - to generate mature sperm. In eutherian mammals, epigenetic information such as DNA methylation is dynamically reprogrammed during... more
Male germ cells undergo two consecutive processes - pre-spermatogenesis and spermatogenesis - to generate mature sperm. In eutherian mammals, epigenetic information such as DNA methylation is dynamically reprogrammed during pre-spermatogenesis, before and during mitotic arrest. In mice, by the time germ cells resume mitosis, the majority of DNA methylation is reprogrammed. The tammar wallaby has a similar pattern of germ cell global DNA methylation reprogramming to that of the mouse during early pre-spermatogenesis. However, early male germline development in the tammar or in any marsupial has not been described previously, so it is unknown whether this is a general feature regulating male germline development or a more recent phenomenon in mammalian evolutionary history. To answer this, we examined germ cell nuclear morphology and mitotic arrest during male germline development in the tammar wallaby (Macropus eugenii), a marsupial that diverged from mice and humans around 160 milli...
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
The formation of the testis or ovary is a critical step in development. Alterations in gonadal development during fetal or postnatal life can lead to intersexuality or infertility. Several model systems have been particularly useful in... more
The formation of the testis or ovary is a critical step in development. Alterations in gonadal development during fetal or postnatal life can lead to intersexuality or infertility. Several model systems have been particularly useful in studying gonadal differentiation, the eutherian mammal and amphibia, fish, and birds. However, marsupials provide a unique opportunity to investigate gonadal development and the interactions of genes and hormones in gonadal differentiation and germ cell development in all mammals. On the one hand the genetic mechanisms appear to be identical to those in eutherian mammals, including the testis-determining SRY gene. On the other hand, marsupials retain in part the plasticity of the amphibian gonad to hormonal manipulation. It is possible to induce female to male and also male to female gonadal sex reversal in marsupials by hormonal manipulation, and oestradiol can induce male germ cells to enter meiosis at the time the oogonia do. In addition, in marsup...
Research Interests:
There is increasing evidence that long non-coding RNAs (lncRNAs) are important for normal reproductive development, yet very few lncRNAs have been identified in phalluses so far. Unlike eutherians, phallus development in the marsupial... more
There is increasing evidence that long non-coding RNAs (lncRNAs) are important for normal reproductive development, yet very few lncRNAs have been identified in phalluses so far. Unlike eutherians, phallus development in the marsupial tammar wallaby occurs post-natally, enabling manipulation not possible in eutherians in which differentiation occurs in utero. We treated with sex steroids to determine the effects of androgen and oestrogen on lncRNA expression during phallus development. Hormonal manipulations altered the coding and non-coding gene expression profile of phalluses. We identified several predicted co-regulatory lncRNAs that appear to be co-expressed with the hormone-responsive candidate genes regulating urethral closure and phallus growth, namely IGF1, AR and ESR1. Interestingly, more than 50% of AR-associated coding genes and lncRNAs were also associated with ESR1. In addition, we identified and validated three novel co-regulatory and hormone-responsive lncRNAs: lnc-BM...
Research Interests:
Large regions of recurrent genomic loss are common in cancers; however, with a few well-characterized exceptions, how they contribute to tumor pathogenesis remains largely obscure. Here we identified primate-restricted imprinting of a... more
Large regions of recurrent genomic loss are common in cancers; however, with a few well-characterized exceptions, how they contribute to tumor pathogenesis remains largely obscure. Here we identified primate-restricted imprinting of a gene cluster on chromosome 20 in the region commonly deleted in chronic myeloid malignancies. We showed that a single heterozygous 20q deletion consistently resulted in the complete loss of expression of the imprinted genes L3MBTL1 and SGK2, indicative of a pathogenetic role for loss of the active paternally inherited locus. Concomitant loss of both L3MBTL1 and SGK2 dysregulated erythropoiesis and megakaryopoiesis, 2 lineages commonly affected in chronic myeloid malignancies, with distinct consequences in each lineage. We demonstrated that L3MBTL1 and SGK2 collaborated in the transcriptional regulation of MYC by influencing different aspects of chromatin structure. L3MBTL1 is known to regulate nucleosomal compaction, and we here showed that SGK2 inacti...
Research Interests:
There is increasing evidence that long non-coding RNAs (lncRNAs) are important for normal reproductive development, yet very few lncRNAs have been identified in phalluses so far. Unlike eutherians, phallus development in the marsupial... more
There is increasing evidence that long non-coding RNAs (lncRNAs) are important for normal reproductive development, yet very few lncRNAs have been identified in phalluses so far. Unlike eutherians, phallus development in the marsupial tammar wallaby occurs post-natally, enabling manipulation not possible in eutherians in which differentiation occurs in utero. We treated with sex steroids to determine the effects of androgen and oestrogen on lncRNA expression during phallus development. Hormonal manipulations altered the coding and non-coding gene expression profile of phalluses. We identified several predicted co-regulatory lncRNAs that appear to be co-expressed with the hormone-responsive candidate genes regulating urethral closure and phallus growth, namely IGF1, AR and ESR1. Interestingly, more than 50% of AR-associated coding genes and lncRNAs were also associated with ESR1. In addition, we identified and validated three novel co-regulatory and hormone-responsive lncRNAs: lnc-BM...
Research Interests:
s with a maximum length of 250 words should be provided for all Original Articles and Reviews, and with 100 words for Short Reports and Case Reports. Figures: Digital illustrations should be sharp with good contrast and color rendition.... more
s with a maximum length of 250 words should be provided for all Original Articles and Reviews, and with 100 words for Short Reports and Case Reports. Figures: Digital illustrations should be sharp with good contrast and color rendition. Resolution for all graphics should be at least 300 dots per inch. We request that all illustrations be in a common format such as .jpg (.jpeg .jpe), .tif (.tiff), .eps or .ppt. Tables must be in Word format. Please use Microsoft Word Table > Insert > Table commands from the menu bar to make tables. Literature cited: References should be quoted in the text as follows: single author: Jones (1999); two authors: Jones and Smith (2000); more than two authors: Jones et al. (2002). The reference list should be arranged alphabetically according to the first author’s surname. Examples of citations are as follows: (1) Jones A, Smith B: The sex determining gene of Tyranosaurus rex. J Ext Rept 7:1–5 (2002). (2) Jones A: Pathology of Sex Determination in Pa...
Research Interests:
Hypospadias is a failure of urethral closure within the penis occurring in 1 in 125 boys at birth and is increasing in frequency. While paracrine hedgehog signalling is implicated in the process of urethral closure, how these factors act... more
Hypospadias is a failure of urethral closure within the penis occurring in 1 in 125 boys at birth and is increasing in frequency. While paracrine hedgehog signalling is implicated in the process of urethral closure, how these factors act on a tissue level to execute closure itself is unknown. This study aimed to understand the role of different hedgehog signalling members in urethral closure. The tammar wallaby (Macropus eugenii) provides a unique system to understand urethral closure as it allows direct treatment of developing offspring because mothers give birth to young before urethral closure begins. Wallaby pouch young were treated with vehicle or oestradiol (known to induce hypospadias in males) and samples subjected to RNAseq for differential expression and gene ontology analyses. Localisation of Sonic Hedgehog (SHH) and Indian Hedgehog (IHH), as well as the transcription factor SOX9, were assessed in normal phallus tissue using immunofluorescence. Normal tissue culture expla...
Research Interests:
Congenital anomalies in phalluses caused by endocrine disruptors have gained a great deal of attention due to its annual increasing rate in males. However, the endocrine-driven molecular regulatory mechanism of abnormal phallus... more
Congenital anomalies in phalluses caused by endocrine disruptors have gained a great deal of attention due to its annual increasing rate in males. However, the endocrine-driven molecular regulatory mechanism of abnormal phallus development is complex and remains largely unknown. Here, we review the direct effect of androgen and oestrogen on molecular regulation in phalluses using the marsupial tammar wallaby, whose phallus differentiation occurs after birth. We summarize and discuss the molecular mechanisms underlying phallus differentiation mediated by sonic hedgehog (SHH) at day 50 pp and phallus elongation mediated by insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3), as well as multiple phallus-regulating genes expressed after day 50 pp. We also identify hormone-responsive long non-coding RNAs (lncRNAs) that are co-expressed with their neighboring coding genes. We show that the activation of SHH and IGF1, mediated by balanced androgen ...
Research Interests:
Australia is home to a unique assembly of mammals – the marsupials and monotremes. Despite this uniqueness, they have been largely ignored by the biomedical scientific community, and yet study of marsupials has contributed to modern... more
Australia is home to a unique assembly of mammals – the marsupials and monotremes. Despite this uniqueness, they have been largely ignored by the biomedical scientific community, and yet study of marsupials has contributed to modern research on reproduction, development, evolution, conservation, molecular and comparative genomics. My lifetime passion for these long-neglected Australian fauna has led to unexpected discoveries and insights that challenged assumptions and opened up new areas of international research. I used a range of disciplinary expertise to pursue the study of these unique mammals. My main experimental species has been the tammar wallaby that I have used as a model species to investigate and understand not only biomedical problems but also to provide knowledge that is critical for the continued conservation and management of Australia’s dwindling native mammals. This model provided more than a few surprises for me and my wonderful team of students, post-docs and co...
Research Interests:
This special issue on women in reproduction that acknowledges some of today’s female trailblazers in the field of reproduction. When most of these women began their careers, there were few, if any, role models for them to follow. Most... more
This special issue on women in reproduction that acknowledges some of today’s female trailblazers in the field of reproduction. When most of these women began their careers, there were few, if any, role models for them to follow. Most reproductive scientists were men; most general practitioners were men; most obstetricians and gynaecologists were men. Fortunately, this sex bias has changed today, but in no small part to the pioneering effort of these and many other women reproductive biologists.
Research Interests:
Research Interests:
In the monovular macropodid marsupial, the tammar wallaby (Macropus eugenii), the cervices are the primary selective barrier to spermatozoa, resulting in differential transport to the non-gravid uterus where a sperm reservoir is... more
In the monovular macropodid marsupial, the tammar wallaby (Macropus eugenii), the cervices are the primary selective barrier to spermatozoa, resulting in differential transport to the non-gravid uterus where a sperm reservoir is established (Tyndale-Biscoe CH and Rodger JC 1978 J. Reprod. Fertil. 52, 37–43). However, due to limited sample size, the dynamics of sperm transport could not be thoroughly examined. In this study, the distribution of spermatozoa, the size of the copulatory plug in the reproductive tract at various times after mating, and the timing of ovulation were characterized in 28 naturally mated female tammars. After the first postpartum (p.p.) mating, adult females were isolated and their reproductive tracts dissected at 0.5, 6, 18, 36, and 40 h post-coitum (p.c.). Each tract was ligated into 13 major anatomical sections, and spermatozoa and eggs were recovered by flushing. Mating occurred 21.7 ± 2.5 h p.p. (mean ± SEM; n = 20) in these animals that were checked fre...
Research Interests: Endocrinology, Genetics, Andrology, Art, Fertility, and 15 moreCell Biology, Cryopreservation, Oogenesis, Embryo, Biological Sciences, Educational, Cloning, Fertilization, Embryonic Development, Folliculogenesis, Embryogenesis, Gametogenesis, Fertilisation, Embryo Development, and Medical and Health Sciences
The development of the mammalian phallus involves hormone-dependent mesenchymal-epithelial signalling mechanisms that contribute to urethral closure and regulation of phallus elongation and growth. In marsupials, most differentiation and... more
The development of the mammalian phallus involves hormone-dependent mesenchymal-epithelial signalling mechanisms that contribute to urethral closure and regulation of phallus elongation and growth. In marsupials, most differentiation and growth of the phallus occurs post-natally, making them amenable to direct hormone treatment. Expression of IGFs, FGFs, EFNB2, MAFB, DLX5 and AP-1 mRNAs in the phallus at day 50 post-partum (pp) were altered after treatment of tammar wallaby young from day 20-40 pp with androgen, oestrogen or after castration at day 25pp. However, the most interesting changes occurred in the IGF pathway genes. Androgen treatment upregulated IGF1 in female phalluses and oestrogen treatment upregulated IGF1 in male phalluses, but it was downregulated by castration. IGFBP3 was higher in female phalluses and downregulated by androgen. IGF1 expression was higher in all untreated male than in female phalluses from day 50 to 150 pp, but IGFBP3 had the reverse pattern. At da...
Research Interests:
Environmental endocrine disruptors (EEDs) that affect androgen or estrogen activity may disrupt gene regulation during normal phallus development to cause hypospadias or a masculinized clitoris. We treated developing male tammar wallabies... more
Environmental endocrine disruptors (EEDs) that affect androgen or estrogen activity may disrupt gene regulation during normal phallus development to cause hypospadias or a masculinized clitoris. We treated developing male tammar wallabies with estrogen and females with androgen from day 20-40 postpartum (pp) during the established androgen imprinting window. Administration of estrogen to males inhibited phallus elongation but had no effect on urethral closure and did not significantly depress testicular androgen synthesis. Androgen treatment during the imprinting window in females did not promote phallus elongation but did initiate urethral closure. Phalluses were collected for transcriptome sequencing at day 50 pp when they first become sexually dimorphic to examine changes in two key signaling pathways, SHH and WNT/β-catenin. SHH mRNA and β-catenin were predominantly expressed in the urethral epithelium in the tammar phallus, as in eutherian mammals. Estrogen treatment and castrat...
Research Interests:
This study aims to develop the Diffusible Iodine-based Contrast-Enhanced CT (diceCT) method for non-destructive imaging of both soft and mineralised tissues. We sought to document the 3D spatio-temporal pattern of mammalian tooth... more
This study aims to develop the Diffusible Iodine-based Contrast-Enhanced CT (diceCT) method for non-destructive imaging of both soft and mineralised tissues. We sought to document the 3D spatio-temporal pattern of mammalian tooth development including multiple tooth classes and generations, using the tammar wallaby (Macropus eugenii) as a model species. We took microCT scans of developing fetuses and pouch young stained using Lugol's Iodine (IKI) contrast agent. Stained versus unstained specimen comparisons were then made to investigate whether staining had improved visualisation of structures. Scan slices were compared to histological sections to confirm the identity of tissues and structures. Tissue layers were digitally segmented to create 3D models. DiceCT dramatically enhanced visual contrast of soft tissues, allowing differentiation between epithelial and mesenchymal layers. Subvolume scans at higher magnification achieved single-cell layer resolution within relatively lar...
Research Interests:
In mammalian pregnancy, the uterus is remodelled to become receptive to embryonic implantation. Since non-invasive placentation in marsupials is likely derived from invasive placentation, and is underpinned by intra-uterine conflict... more
In mammalian pregnancy, the uterus is remodelled to become receptive to embryonic implantation. Since non-invasive placentation in marsupials is likely derived from invasive placentation, and is underpinned by intra-uterine conflict between mother and embryo, species with non-invasive placentation may employ a variety of molecular mechanisms to maintain an intact uterine epithelium and to prevent embryonic invasion. Identifying such modifications to the uterine epithelium of marsupial species with non-invasive placentation is key to understanding how conflict is mediated during pregnancy in different mammalian groups. Desmoglein-2, involved in maintaining lateral cell-cell adhesion of the uterine epithelium, is redistributed before implantation to facilitate embryo invasion in mammals with invasive placentation. We identified localization patterns of this cell adhesion molecule throughout pregnancy in two marsupial species with non-invasive placentation, the tammar wallaby (Macropus...
Research Interests:
Research Interests:
The resumption of ovulation and menstruation in a well-nourished population of women breastfeeding for an extended period of time**Supported by National Health and Medical Research Council grant 840200, Canberra, Australian Capital Territory, Australia; Lalor Foundation, Wilmington, Delaware; Fam...more
We have studied a large group of Australian women breastfeeding for an extended period of time to determine the duration of lactational anovulation (n = 89) and amenorrhea (n = 101). Salivary progesterone assays were used to determine... more
We have studied a large group of Australian women breastfeeding for an extended period of time to determine the duration of lactational anovulation (n = 89) and amenorrhea (n = 101). Salivary progesterone assays were used to determine ovulation. These women had a mean of 322 days of anovulation and 289 days amenorrhea. Less than 20% had ovulated and less than 25% had menstruated by 6 months postpartum. The latest ovulation was at 750 days and the latest menstruation at 698 days. There was no significant correlation between any measure of maternal nutritional status and the duration of anovulation or amenorrhea. Neither the time of first supplement introduction to the baby nor the amount of supplement given was an accurate predictor of the return of ovulation or menstruation. However, our results clearly show that lactational amenorrhea can provide good protection against pregnancy in the 1st 6 months postpartum, even in well-nourished women who are giving their babies supplemental feeds.
Research Interests:
Research Interests:
Embryonic diapause is a period of developmental arrest which requires coordination of a molecular cross-talk between the endometrium and blastocyst to ensure a successful reactivation, but the exact mechanisms are undefined. The... more
Embryonic diapause is a period of developmental arrest which requires coordination of a molecular cross-talk between the endometrium and blastocyst to ensure a successful reactivation, but the exact mechanisms are undefined. The objectives of this study were to screen the tammar blastocyst for potential diapause control factors and to investigate the potential for members of the epidermal growth factor (EGF) family to coordinate reactivation. A select number of factors were also examined in the mink to determine whether their expression patterns were conserved across diapause species. The full-length sequences of the tammar genes of interest were first cloned to establish their level of sequence conservation with other mammals. The uterine expression of EGF family members EGF and heparin-binding EGF (HBEGF) and their receptors (EGFR and erb-b2 receptor tyrosine kinase 4 (ERBB4)) was determined by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohistoch...
Research Interests:
The marsupial tammar wallaby has the longest period of embryonic diapause of any mammal, up to 11 months, during which there is no cell division or blastocyst growth. Since the blastocyst in diapause is surrounded by acellular coats, the... more
The marsupial tammar wallaby has the longest period of embryonic diapause of any mammal, up to 11 months, during which there is no cell division or blastocyst growth. Since the blastocyst in diapause is surrounded by acellular coats, the signals that maintain or terminate diapause involve factors which reside in uterine secretions. The nature of such factors remains to be resolved. In this study uterine flushings (UF) were used to assess changes in uterine secretions of tammars using liquid chromatography-mass spectrometry (LC-MS/MS) during diapause (day 0 & 3) and reactivation days 4, 5, 6, 8, 9, 11 and 24 after removal of pouch young (RPY), which initiates embryonic development. This study supports earlier suggestions that the presence of specific factors stimulate reactivation, early embryonic growth and cell proliferation. A mitogen, hepatoma-derived growth factor, and soluble epidermal growth factor receptors were observed from d3 until at least d11 RPY when these secreted prot...
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
The blastocyst is a mammalian invention that carries the embryo from cleavage to gastrulation. For such a simple structure, it exhibits remarkable diversity in its mode of formation, morphology, longevity, and intimacy with the uterine... more
The blastocyst is a mammalian invention that carries the embryo from cleavage to gastrulation. For such a simple structure, it exhibits remarkable diversity in its mode of formation, morphology, longevity, and intimacy with the uterine endometrium. This review explores this diversity in the light of the evolution of viviparity, comparing the three main groups of mammals: monotremes, marsupials, and eutherians. The principal drivers in blastocyst evolution were loss of yolk coupled with evolution of the placenta. An important outcome of blastocyst development is differentiation of two extraembryonic lineages (trophoblast and hypoblast) that contribute to the placenta. While in many species trophoblast segregation is often coupled with blastocyst formation, in marsupials and at least some Afrotherians, these events do not coincide. Thus, many questions regarding the conservation of molecular mechanisms controlling these events are of great interest but currently unresolved. For furthe...
Research Interests:
Research Interests:
ABSTRACT
Research Interests:
Research Interests:
Research Interests:
Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development Renfree et al. Renfree et al. Genome Biology 2011, 12:R81