Dendritic cells enter lymph vessels by hyaluronan-mediated docking to the endothelial receptor LYVE-1.

Trafficking of tissue dendritic cells (DCs) via lymph is critical for the generation of cellular immune responses in draining lymph nodes (LNs). In the current study we found that DCs docked to the basolateral surface of lymphatic vessels and transited to the lumen through hyaluronan-mediated interactions with the lymph-specific endothelial receptor LYVE-1, in dynamic transmigratory-cup-like structures. Furthermore, we show that targeted deletion of the gene Lyve1, antibody blockade or depletion of the DC hyaluronan coat not only delayed lymphatic trafficking of dermal DCs but also blunted their capacity to prime CD8+ T cell responses in skin-draining LNs. Our findings uncovered a previously unknown function for LYVE-1 and show that transit through the lymphatic network is initiated by the recognition of leukocyte-derived hyaluronan.

The structural basis for control of eukaryotic protein kinases.

Eukaryotic protein kinases are key regulators of cell processes. Comparison of the structures of protein kinase domains, both alone and in complexes, allows generalizations to be made about the mechanisms that regulate protein kinase activation. Protein kinases in the active state adopt a catalytically competent conformation upon binding of both the ATP and peptide substrates that has led to an understanding of the catalytic mechanism. Docking sites remote from the catalytic site are a key feature of several substrate recognition complexes. Mechanisms for kinase activation through phosphorylation, additional domains or subunits, by scaffolding proteins and by kinase dimerization are discussed.

Hyaluronan Receptor LYVE-1-Expressing Macrophages Maintain Arterial Tone through Hyaluronan-Mediated Regulation of Smooth Muscle Cell Collagen.

The maintenance of appropriate arterial tone is critically important for normal physiological arterial function. However, the cellular and molecular mechanisms remain poorly defined. Here, we have shown that in the mouse aorta, resident macrophages prevented arterial stiffness and collagen deposition in the steady state. Using phenotyping, transcriptional profiling, and targeted deletion of Csf1r, we have demonstrated that these macrophages-which are a feature of blood vessels invested with smooth muscle cells (SMCs) in both mouse and human tissues-expressed the hyaluronan (HA) receptor LYVE-l. Furthermore, we have shown they possessed the unique ability to modulate collagen expression in SMCs by matrix metalloproteinase MMP-9-dependent proteolysis through engagement of LYVE-1 with the HA pericellular matrix of SMCs. Our study has unveiled a hitherto unknown homeostatic contribution of arterial LYVE-1+ macrophages through the control of collagen production by SMCs and has identified a function of LYVE-1 in leukocytes.

Positive postpartum well-being: What works for women.

BACKGROUND: Women's experiences of pregnancy, birth and motherhood extend beyond healthcare provision and the immediate postpartum. Women's social, cultural and political environments shape the positive or negative effects of their experiences through this transition. However, there is limited research concerning the factors that women identify as being protective or promotive of maternal well-being in the perinatal period and motherhood transition. OBJECTIVE: To explore women's views on the factors within healthcare, social, cultural, organizational, environmental and political domains that do or can work well in creating positive perinatal experiences. DESIGN, SETTING AND PARTICIPANTS: A qualitative descriptive study with embedded public and participant involvement (PPI). Participants were 24 women who were maternity care service users giving birth in Ireland. RESULTS: Three themes were developed. The first theme, 'tone of care', related to women's interactions with and attitudes of healthcare professionals in setting the tone for the care they experienced. The second theme, 'postpartum presence and support', concerned the professional postpartum supports and services that women found beneficial in the motherhood transition. The final theme, 'flexibility for new families' addresses social and organizational issues around parents returning to paid employment. DISCUSSION AND CONCLUSION: Women suggested multiple avenues for promoting positive perinatal experiences for women giving birth in Ireland, which may be implemented at healthcare and policy levels. Women identified that maternal health education focuses on supporting informed decision-making processes as a positive and worry-alleviating resource. Additionally, women valued being met by healthcare professionals who regard women as the decision makers in their care experience. Exchanges in which healthcare professionals validate and encourage women in their mothering role and actively involve their partners as caregivers left lasting positive impressions. Extended and professional postpartum support was a common issue, and phone lines or drop-in clinics were suggested as invaluable and affirming assets where women could access personalized support with healthcare professionals who had the knowledge and skills to genuinely approach women's concerns. Social and organizational considerations involved supporting parents to balance their responsibilities as new or growing families in the return to work. PUBLIC OR PATIENT CONTRIBUTION: Maternity care service users were involved in the interviews and manuscript preparation.

In Sickness and in Health: The Immunological Roles of the Lymphatic System.

The lymphatic system plays crucial roles in immunity far beyond those of simply providing conduits for leukocytes and antigens in lymph fluid. Endothelial cells within this vasculature are distinct and highly specialized to perform roles based upon their location. Afferent lymphatic capillaries have unique intercellular junctions for efficient uptake of fluid and macromolecules, while expressing chemotactic and adhesion molecules that permit selective trafficking of specific immune cell subsets. Moreover, in response to events within peripheral tissue such as inflammation or infection, soluble factors from lymphatic endothelial cells exert "remote control" to modulate leukocyte migration across high endothelial venules from the blood to lymph nodes draining the tissue. These immune hubs are highly organized and perfectly arrayed to survey antigens from peripheral tissue while optimizing encounters between antigen-presenting cells and cognate lymphocytes. Furthermore, subsets of lymphatic endothelial cells exhibit differences in gene expression relating to specific functions and locality within the lymph node, facilitating both innate and acquired immune responses through antigen presentation, lymph node remodeling and regulation of leukocyte entry and exit. This review details the immune cell subsets in afferent and efferent lymph, and explores the mechanisms by which endothelial cells of the lymphatic system regulate such trafficking, for immune surveillance and tolerance during steady-state conditions, and in response to infection, acute and chronic inflammation, and subsequent resolution.

A phenotypic switch in the dispersal strategy of breast cancer cells selected for metastatic colonization.

An important question in cancer evolution concerns which traits make a cell likely to successfully metastasize. Cell motility phenotypes, mediated by cell shape change, are strong candidates. We experimentally evolved breast cancer cells in vitro for metastatic capability, using selective regimes designed to simulate stages of metastasis, then quantified their motility behaviours using computer vision. All evolved lines showed changes to motility phenotypes, and we have identified a previously unknown density-dependent motility phenotype only seen in cells selected for colonization of decellularized lung tissue. These cells increase their rate of morphological change with an increase in migration speed when local cell density is high. However, when the local cell density is low, we find the opposite relationship: the rate of morphological change decreases with an increase in migration speed. Neither the ancestral population, nor cells selected for their ability to escape or invade extracellular matrix-like environments, displays this dynamic behavioural switch. Our results suggest that cells capable of distant-site colonization may be characterized by dynamic morphological phenotypes and the capacity to respond to the local social environment.

Acceptability of screening for pregnancy intention in general practice: a population survey of people of reproductive age.

BACKGROUND: Optimal parental preconception health benefits reproductive outcomes. However, preconception health promotion is not routinely offered in primary health care settings to people of reproductive age. The aim was to gauge the planned preconception health behaviours and attitudes towards being asked about pregnancy intention by a general practitioner (GP) among people of reproductive age in Australia. METHOD: The research was conducted on a single wave of Australia's first and only probability-based online panel, Life in Australia™. Members of the Life in Australia™ panel are Australian residents aged 18 years or over. All active members between the ages of 18 and 45 years were eligible to participate. Eligible panel members were invited to complete a survey about fertility and childbearing. Data were collected from 18 February to 4 March 2019. RESULTS: In all 965 female and male members of Life in Australia™ aged between 18 and 45 years were invited to complete the survey. Of these, 716 (74.2%) agreed. Most respondents indicated that if they were planning to have a child they would try to optimise their preconception health by adopting a healthier diet (80%), seeing a GP for a health check-up (78%), reducing alcohol consumption (78% of those consuming alcohol), getting fitter (73%), and stopping smoking (70% of smokers). Three in four (74%) stated that they would not mind if their GP asked them about their pregnancy intentions. CONCLUSION: Findings suggests that routinely asking people of reproductive age about their pregnancy intentions and advising those who are planning pregnancy about what they can do to ensure optimal preconception health would be acceptable to most people and may improve reproductive outcomes.

Having a baby in your 40s with assisted reproductive technology: The reproductive dilemma of autologous versus donor oocytes.

BACKGROUND: Increasing numbers of women ≥40 years old are accessing assisted reproductive technology (ART) due to age-related infertility. There is limited population-based evidence about the impact on the cumulative live birth rate (CLBR) of women aged ≥40 years using their own oocytes, compared to women of a similar age, using donor oocytes. AIMS: To compare the CLBR for women ≥40 years undergoing ART using autologous oocytes and women of similar age using donor oocytes. MATERIALS AND METHODS: This population-based retrospective cohort study used data from all women aged ≥40 years undergoing ART with donated (n = 987) or autologous oocytes (n = 19 170) in Victoria, Australia between 2009 and 2016. A discrete-time survival model was used to evaluate the CLBR following ART with donor or autologous oocytes. The odds ratio, adjusted for woman's age; male age; parity; cause of infertility; and the associated 95% confidence intervals (CI), were calculated. The numbers needed to be exposed (NNEs) were calculated from the adjusted odds ratio (aOR) and the CLBR in the autologous group. RESULTS: The CLBR ranged from 28.6 to 42.5% in the donor group and from 12.5% to 1.4% in the autologous group. The discrete-time survival analysis with 95% CI demonstrated significant aOR on CLBR across all ages (range aOR: 2.56, 95% CI: 1.62-4.01 to aOR: 15.40, 95% CI: 9.10-26.04). CONCLUSIONS: Women aged ≥40 years, using donor oocytes had a significantly higher CLBR than women using autologous oocytes. The findings can be used when counselling women ≥40 years about their ART treatment options and to inform public policy.

A brief update on the evidence supporting the treatment of infertility in polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is complex with reproductive, metabolic and psychological features. Infertility is a prevalent presenting feature of PCOS with approximately 75% of these women suffering infertility due to anovulation, making PCOS by far the most common cause of anovulatory infertility. Previous guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated. AIMS: This review paper aims to provide a brief update on the best available and most current research evidence supporting the treatment of PCOS which informed the recommendations in the assessment and treatment of infertility section of the international evidence-based guideline on PCOS 2018. MATERIALS AND METHODS: International evidence-based guideline development engaged professional societies and consumer organisations with multidisciplinary experts and women with PCOS directly involved at all stages. RESULTS: Lifestyle change alone is considered the first-line treatment for the management of infertile anovulatory PCOS women who are overweight or obese. Letrozole should now be considered first-line pharmacological treatment for ovulation induction to improve fertility outcomes. Clomiphene citrate alone and metformin alone could also be used as first-line pharmacological therapy, although both are less effective than letrozole and metformin is less effective than clomiphene citrate in obese women. Gonadotrophins or laparoscopic ovarian surgery are usually second-line ovulation induction therapies. In the absence of an absolute indication for in vitro fertilisation (IVF) / intracytoplasmic sperm injection, women with PCOS and anovulatory infertility could be offered IVF as third-line therapy where first- or second-line ovulation induction therapies have failed. CONCLUSION: This review provides the best available evidence informing recommendations (along with clinical expertise and consumer preference) which provide clinicians with clear advice on best practice for the management of infertile women with PCOS.

Quality of information about success rates provided on assisted reproductive technology clinic websites in Australia and New Zealand.

BACKGROUND: Many factors influence the chance of having a baby with assisted reproductive technologies (ART). A 2016 Australian Competition and Consumer Commission (ACCC) investigation concluded that ART clinics needed to improve the quality of information they provide about chance of ART success. AIM: To evaluate changes in the quality of information about success rates provided on the websites of ART clinics in Australia and New Zealand before and after the ACCC investigation. MATERIALS AND METHOD: Desktop audits of websites of ART clinics in Australia and New Zealand were conducted in 2016 and 2017 and available information about success rates was scored using a matrix with eight variables and a possible range of scores of 0-9. RESULTS: Of the 54 clinic websites identified in 2016, 32 had unique information and were eligible to be audited. Of these, 29 were also eligible to be audited in 2017. While there was a slight improvement in the mean score from 2016 to 2017 (4.93-5.28), this was not statistically significantly different. Of the 29 clinics, 14 had the same score on both occasions, 10 had a higher and five a lower information quality score in 2017. CONCLUSIONS: To allow people who consider ART to make informed decisions about treatment they need comprehensive and accurate information about what treatment entails and what the likely outcomes are. As measured by a scoring matrix, most ART clinics had not improved the quality of the information about success rates following the ACCC investigation.

Resource competition promotes tumour expansion in experimentally evolved cancer.

BACKGROUND: Tumour progression involves a series of phenotypic changes to cancer cells, each of which presents therapeutic targets. Here, using techniques adapted from microbial experimental evolution, we investigate the evolution of tumour spreading - a precursor for metastasis and tissue invasion - in environments with varied resource supply. Evolutionary theory predicts that competition for resources within a population will select for individuals to move away from a natal site (i.e. disperse), facilitating the colonisation of unexploited resources and decreasing competition between kin. RESULTS: After approximately 100 generations in environments with low resource supply, we find that MCF7 breast cancer spheroids (small in vitro tumours) show increased spreading. Conversely, spreading slows compared to the ancestor where resource supply is high. Common garden experiments confirm that the evolutionary responses differ between selection lines; with lines evolved under low resource supply showing phenotypic plasticity in spheroid spreading rate. These differences in spreading behaviour between selection lines are heritable (stable across multiple generations), and show that the divergently evolved lines differ in their response to resource supply. CONCLUSIONS: We observe dispersal-like behaviour and an increased sensitivity to resource availability in our selection lines, which may be a response to selection, or alternatively may be due to epigenetic changes, provoked by prolonged resource limitation, that have persisted across many cell generations. Different clinical strategies may be needed depending on whether or not tumour progression is due to natural selection. This study highlights the effectiveness of experimental evolution approaches in cancer cell populations and demonstrates how simple model systems might enable us to observe and measure key selective drivers of clinically important traits.

Rapid Lymphatic Dissemination of Encapsulated Group A Streptococci via Lymphatic Vessel Endothelial Receptor-1 Interaction.

The host lymphatic network represents an important conduit for pathogen dissemination. Indeed, the lethal human pathogen group A streptococcus has a predilection to induce pathology in the lymphatic system and draining lymph nodes, however the underlying basis and subsequent consequences for disease outcome are currently unknown. Here we report that the hyaluronan capsule of group A streptococci is a crucial virulence determinant for lymphatic tropism in vivo, and further, we identify the lymphatic vessel endothelial receptor-1 as the critical host receptor for capsular hyaluronan in the lymphatic system. Interference with this interaction in vivo impeded bacterial dissemination to local draining lymph nodes and, in the case of a hyper-encapsulated M18 strain, redirected streptococcal entry into the blood circulation, suggesting a pivotal role in the manifestation of streptococcal infections. Our results reveal a novel function for bacterial capsular polysaccharide in directing lymphatic tropism, with potential implications for disease pathology.

The chemokine CX3CL1 promotes trafficking of dendritic cells through inflamed lymphatics.

Tissue inflammation is characterised by increased trafficking of antigen-loaded dendritic cells (DCs) from the periphery via afferent lymphatics to draining lymph nodes, with a resulting stimulation of ongoing immune responses. Transmigration across lymphatic endothelium constitutes the first step in this process and is known to involve the chemokine CCL21 and its receptor CCR7. However, the precise details of DC transit remain obscure and it is likely that additional chemokine-receptor pairs have roles in lymphatic vessel entry. Here, we report that the transmembrane chemokine CX3CL1 (fractalkine) is induced in inflamed lymphatic endothelium, both in vitro in TNF-α-treated human dermal lymphatic endothelial cells (HDLECs) and in vivo in a mouse model of skin hypersensitivity. However, unlike blood endothelial cells, which express predominantly transmembrane CX3CL1 as a leukocyte adhesion molecule, HDLECs shed virtually all CX3CL1 at their basolateral surface through matrix metalloproteinases. We show for the first time that both recombinant soluble CX3CL1 and endogenous secreted CX3CL1 promote basolateral-to-luminal migration of DCs across HDLEC monolayers in vitro. Furthermore, we show in vivo that neutralising antibodies against CX3CL1 dramatically reduce allergen-induced trafficking of cutaneous DCs to draining lymph nodes as assessed by FITC skin painting in mice. Finally, we show that deletion of the CX3CL1 receptor in Cx3cr1(-/-) DCs results in markedly delayed lymphatic trafficking in vivo and impaired translymphatic migration in vitro, thus establishing a previously unrecognised role for this atypical chemokine in regulating DC trafficking through the lymphatics.

Bacterial pathogen evolution: breaking news.

The immense social and economic impact of bacterial pathogens, from drug-resistant infections in hospitals to the devastation of agricultural resources, has resulted in major investment to understand the causes and consequences of pathogen evolution. Recent genome sequencing projects have provided insight into the evolution of bacterial genome structures; revealing the impact of mobile DNA on genome restructuring and pathogenicity. Sequencing of multiple genomes of related strains has enabled the delineation of pathogen evolution and facilitated the tracking of bacterial pathogens globally. Other recent theoretical and empirical studies have shown that pathogen evolution is significantly influenced by ecological factors, such as the distribution of hosts within the environment and the effects of co-infection. We suggest that the time is ripe for experimentalists to use genomics in conjunction with evolutionary ecology experiments to further understanding of how bacterial pathogens evolve.

Control of dendritic cell trafficking in lymphatics by chemokines.

Dendritic cells (DCs) are crucial participants in maintaining immune surveillance of the periphery and initiating primary immune responses within the draining lymph nodes. The afferent lymphatic vessels provide a conduit for this essential trafficking and, as this review will describe, play an active role in regulating DC migration. Afferent lymphatic capillaries support constitutive trafficking of DCs from resting, non-inflamed tissue, to maintain tolerance against self-antigen and to provide immune surveillance. Following exposure to pathogens or pro-inflammatory cytokines, DCs mature from phagocytes to professional antigen-presenting cells, whilst the lymphatic endothelium adopts an activated phenotype to support the ensuing increase in leukocyte trafficking. The lymphatic endothelial-derived chemokine CCL21 plays a well-characterized role in directing migration of CCR7+ DC in both resting and acute inflammatory conditions. However, efficient trafficking of DCs from inflamed tissue also demands additional chemokine-receptor pairs. Thus, entry of DCs to activated lymphatic vessels is an intricately regulated multi-step process involving numerous chemokines and adhesion molecules.

The biosurfactant viscosin produced by Pseudomonas fluorescens SBW25 aids spreading motility and plant growth promotion.

Food security depends on enhancing production and reducing loss to pests and pathogens. A promising alternative to agrochemicals is the use of plant growth-promoting rhizobacteria (PGPR), which are commonly associated with many, if not all, plant species. However, exploiting the benefits of PGPRs requires knowledge of bacterial function and an in-depth understanding of plant-bacteria associations. Motility is important for colonization efficiency and microbial fitness in the plant environment, but the mechanisms employed by bacteria on and around plants are not well understood. We describe and investigate an atypical mode of motility in Pseudomonas fluorescens SBW25 that was revealed only after flagellum production was eliminated by deletion of the master regulator fleQ. Our results suggest that this 'spidery spreading' is a type of surface motility. Transposon mutagenesis of SBW25ΔfleQ (SBW25Q) produced mutants, defective in viscosin production, and surface spreading was also abolished. Genetic analysis indicated growth-dependency, production of viscosin, and several potential regulatory and secretory systems involved in the spidery spreading phenotype. Moreover, viscosin both increases efficiency of surface spreading over the plant root and protects germinating seedlings in soil infected with the plant pathogen Pythium. Thus, viscosin could be a useful target for biotechnological development of plant growth promotion agents.

Proposed legislative change mandating retrospective release of identifying information: consultation with donors and Government response.

STUDY QUESTION: How do gamete donors who presumed they could remain anonymous respond to proposed legislation to retrospectively remove anonymity? SUMMARY ANSWER: A little more than half of the donors opposed the recommendation to introduce legislation to remove donor anonymity with retrospective effect. WHAT IS KNOWN ALREADY: An increasing proportion of parents disclose their origins to their donor-conceived children and growing numbers of donor-conceived adults are aware of how they were conceived. Research indicates that access to information about the donor is important to donor-conceived people. However, worldwide most donor-conceived people are unable to find any identifying information about the donor because of the practice of anonymous gamete donation. STUDY DESIGN, SIZE, DURATION: This study adopted a qualitative research model using semi-structured interviews with gamete donors that included open questions. Interviews with 42 volunteers were conducted between December 2012 and February 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: Before 1998 gamete donors in Victoria, Australia, were able to remain anonymous. Pre-1998 donors were invited through an advertising campaign to be interviewed about their views on a recommendation that legislation mandating retrospective release of identifying information be introduced. MAIN RESULTS AND THE ROLE OF CHANCE: Donors were almost evenly split between those who supported and those who rejected the recommendation to introduce legislation to remove donor anonymity with retrospective effect. About half of the donors who rejected the recommendation suggested the compromise of persuading donors voluntarily to release information (whether identifying or non-identifying) to donor-conceived people. These donors were themselves willing to supply information to their donor offspring. The findings of this study informed the Victorian Government's response to the proposed legislative change. While acknowledging donor-conceived people's right of access to information about their donors, the Government decided that identifying information should be released only with the consent of donors and that donors should be encouraged to allow themselves to be identifiable to their donor offspring. LIMITATIONS, REASONS FOR CAUTION: There is no way of knowing whether participants were representative of all pre-1998 donors. WIDER IMPLICATIONS OF THE FINDINGS: The balancing of donors' and donor-conceived people's rights requires utmost sensitivity. All over the world, increasing numbers of donor-conceived people are reaching adulthood; of those who are aware of their mode of conception, some are likely to have a strong wish to know the identity of their donors. Legislators and policy-makers in jurisdictions permitting anonymous gamete donations will need to respond when these desires are expressed, and may choose to be guided by the model of consultation described in this paper. STUDY FUNDING/COMPETING INTERESTS: The study was funded by the Victorian Department of Health. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Gamete donors' expectations and experiences of contact with their donor offspring.

STUDY QUESTION: What are the expectations and experiences of anonymous gamete donors about contact with their donor offspring? SUMMARY ANSWER: Rather than consistently wanting to remain distant from their donor offspring, donors' expectations and experiences of contact with donor offspring ranged from none to a close personal relationship. WHAT IS KNOWN ALREADY: Donor conception is part of assisted reproduction in many countries, but little is known about its continuing influence on gamete donors' lives. STUDY DESIGN, SIZE, DURATION: A qualitative research model appropriate for understanding participants' views was employed; semi-structured interviews were conducted during January-March 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: Before 1998, gamete donors in Victoria, Australia, were subject to evolving legislation that allowed them to remain anonymous or (from 1988) to consent to the release of identifying information. An opportunity to increase knowledge of donors' expectations and experiences of contact with their donor offspring recently arose in Victoria when a recommendation was made to introduce mandatory identification of donors on request from their donor offspring, with retrospective effect. Pre-1998 donors were invited through an advertising campaign to be interviewed about their views, experiences and expectations; 36 sperm donors and 6 egg donors participated. MAIN RESULTS AND THE ROLE OF CHANCE: This research is unusual in achieving participation by donors who would not normally identify themselves to researchers or government inquiries. Qualitative thematic analysis revealed that most donors did not characterize themselves as parents of their donor offspring. Donors' expectations and experiences of contact with donor offspring ranged from none to a close personal relationship. LIMITATIONS, REASONS FOR CAUTION: It is not possible to establish whether participants were representative of all pre-1998 donors. WIDER IMPLICATIONS OF THE FINDINGS: Anonymous donors' needs and desires are not homogeneous; policy and practice should be sensitive and responsive to a wide range of circumstances and preferences. Decisions made to restrict or facilitate contact or the exchange of information have ramifications for donors as well as for donor-conceived people. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Victorian Department of Health. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Barriers for domestic surrogacy and challenges of transnational surrogacy in the context of Australians undertaking surrogacy in India.

The ethical, social, psychological, legal and financial complexities associated with cross-border travel for reproductive services are gaining attention internationally. Travel abroad for surrogacy, and the transfer of gametes or embryos between countries for use in a surrogacy arrangement, can create conflict in relation to the rights of the parties involved: commissioning parents, surrogates and their families, gamete and embryo donors, and children born as a result of the arrangement. Australian surrogacy laws are restrictive and limit access to domestic surrogacy. Despite the introduction of laws in some Australian jurisdictions that penalise residents entering into international commercial surrogacy arrangements, hundreds of Australians resort to surrogacy arrangements in India and other countries each year. This article discusses legislation, policy and practice as they relate to Australians' use of surrogacy in India. It reviews current surrogacy-related legislation and regulation in Australia and India and existing evidence about the challenges posed by transnational surrogacy, and considers how restrictive Australian legislation may contribute to the number of Australians undertaking surrogacy in India.