Recent advances in reproductive research in Australia and New Zealand: highlights from the Annual Meeting of the Society for Reproductive Biology, 2022

Speakers: Jade Le Grice, Maree Toombs, Cameron D. Young, and Kirsty Pringle

For the first time, the SRB held an ‘Indigenous Reproductive Health Forum’ to showcase research conducted across Australia and New Zealand improving the health outcomes of First Nations peoples. This forum highlighted the benefits of including First Nations peoples in study conception and design and in implementation of research findings within the community, in addition to the importance of cultural sensitivity. Across the diverse topics presented, a single takeaway message emerged: consult First Nations peoples about the research that impacts them, and let the research be guided by the community and their needs.

Indigenous Aboriginal and Torres Strait Islander (First Nations) Australians have high rates of health issues, including chronic diseases and reduced life expectancy, compared to migrant and settler populations (Nolan-Isles et al. 2021). They also experience high rates of common mental health disorders such as depression (Farah Nasir et al. 2021), trauma, and post-traumatic stress disorder (Nasir et al. 2021). Despite this, there is still a lack of access to health services in First Nations communities in Australia. Professor Maree Toombs’ (University of Queensland) research aims to improve access to primary healthcare, particularly mental health services, for First Nations peoples. Her work situates Indigenous peoples at the centre of their own care, illustrating the power of asking the community for their input in regard to what they need. The Mobile Outreach Boomerang (MOB) van run by First Nations healthcare workers, provides primary healthcare to rural First Nations communities. The uptake of this service by the community was so impactful that additional funding from the New South Wales (NSW) government was secured to establish a fixed clinic. Through this healthcare service, the community voiced a need for a suicide intervention program that acted in real time and without judgement (Farah Nasir et al. 2021). Professor Toombs developed the Indigenous-Applied Suicide Intervention Skills Training program (I-ASIST), a suicide intervention model provided in partnership with Livingworks Australia (Farah Nasir et al. 2021). This program has trained over 10 000 people in 90 communities, giving the community a set of critical skills in mental healthcare to support their loved ones when they most need it. These projects demonstrate the positive outcomes of embracing collaborative partnerships with First Nations communities.

Associate Professor Kirsty Pringle’s (University of Newcastle) work in rural NSW also centres around addressing disparities in health outcomes in First Nations communities, with a focus on developing positive and sustainable interventions to improve health outcomes for First Nations mothers and babies. The Gomeroi-Gaaynggal study ran for 10 years in Tamworth (2009–2019), successfully recruiting more than 400 mothers carrying First Nations babies. A critical part of the study design was the development of the Gomeroi-Gaaynggal Advisory Committee to consult on research direction and approval for dissemination of research findings to the broader research community. The study ran alongside an Arts Health program overseen by an Aboriginal Elder and artist in residence, all of which was embedded in the local Gomeroi community to build capacity beyond the lifespan of the study. One key finding was that while the majority of mothers (86%) initiate breastfeeding, the median duration was just 1.4 months (Ashman et al. 2016). Rapid discontinuation of breastfeeding is corroborated by additional studies in the field, representative of other First Nations communities across Australia (Craig et al. 2011; Brown et al. 2019). Working with the Gomeroi community, Associate Professor Pringle and her team are now moving toward building capacity in the community to mentor mothers and encourage longer periods of breastfeeding. By partnering with the Local Aboriginal Land Council and Aboriginal Medical Service, this next phase of the Gomeroi-Gaaynggal study will further improve outcomes for First Nations mothers and babies for better long-term health. Lastly, Associate Professor Pringle highlighted the importance of providing adequate context for the findings of her studies, ensuring there is a distinction from the ongoing impacts of colonisation, and the importance of First Nations healthcare workers in communities to bridge barriers in access to care.

Dr Jade Le Grice (University of Auckland) is working to identify the major challenges of equitable access to public and private fertility services and equitable care outcomes for Māori and Pacific peoples in New Zealand. The ability to contribute to the next generation of whānau (extended family group) is culturally significant for many Māori and Pacific peoples (Rarere 2022). However, members of these communities often face barriers when trying to access fertility services (Righarts et al. 2021). Dr Le Grice’s research has highlighted the cultural and structural barriers such as the use of body mass index as a determinant for access to fertility treatment. This often acts as an exclusion measure that disproportionally impacts Māori and Pacific peoples’ access to publicly funded fertility care (Parker and Le Grice 2022; Shaw and Fehoko 2023). Supported by Fertility New Zealand and the University of Auckland, she is currently focussing on the first-hand experiences of Māori and Pacific peoples with infertility in accessing fertility services, and their health outcomes. This has involved community-driven conversations in six Hui (Māori assembly) focus groups (19 Māori and Pacific participants) and findings thus far have highlighted the need to harness First Nations knowledge to provide holistic pathways for care and healing to support Māori and Pacific people experiencing infertility.

Finally, Cameron Young (University of Otago) highlighted the importance of understanding cultural sensitives when designing research projects, particularly in sexual and reproductive health. Indeed, approaching conversations that include topics like sexuality and reproduction in a Pacific community is very complex. These topics are considered tapu (sacred, forbidden) and can influence health behaviour, often due to discomfort or to avoid shame. Mr Young is exploring the views of Pacific youth on sexuality and reproduction (Young et al. 2022). A project of this nature requires discrete care to minimise harm. To address this, he has revitalised the Fonofale Pacific health model that is traditionally centred around the Pacific concepts of family and culture (Pulotu-Endemann 1995). The inclusion of tapu and noa (ordinary, normal) recognises the complexity of Pacific people’s health and the holistic approach needed to address prominent health issues (Young et al. 2022). Using the analogy of a three-layered cake, he described three important considerations for designing research projects that involve Pacific peoples; these principles can be applied to the design of all relevant research projects. Firstly, an acknowledgement of your worldview and how this may differ from the worldview of Pacific peoples. Secondly, identifying the aspirations of the project and matching these to the aspirations of the Pacific communities. Finally, adopting research methodologies that reflect the community. The Kakala and Talanoa methods are excellent examples of Pacific methodologies that inherently centre the aspirations of Pacific peoples in the research project. By collating these key messages, Mr Young provided a framework for researchers to design culturally sensitive research projects that tackle a variety of scientific questions.

The forum concluded with a panel discussion centred around the intricacies of research projects involving First Nations communities, including data governance. All panel members stressed the importance of communicating summaries of the research and sharing data with the community. Overall, this research demonstrated benefits to health outcomes when First Nations peoples are empowered to engage with and guide the trajectory of health research within their communities.

Speakers: Simon Clulow, Isabel Castro, Stephen Frankenberg, and Donna Bond

Invasive species have a significant, destructive impact on the unique flora and fauna of both Australia and New Zealand. This, together with difficulties that arise from trying to protect typically understudied species, often render conservation efforts ineffective. In this session, four prominent scientists discussed ways to increase conservation success, including ethical management of invasive species and improving understanding of the reproductive biology of vulnerable native species. Challenges and recent advances in the conservation of amphibians, reptiles, and the New Zealand kiwi, as well as novel strides towards control of invasive pest species by gene drive technology and long read methylation sequencing were highlighted in the symposium.

Over 50% of amphibian and 20% of reptilian species are endangered, requiring intervention to preserve genetic diversity and prevent extinction (Bower et al. 2017). The unique modes of fertilisation (internal, external, or parthenogenesis) and reproductive strategies (i.e. oviparity vs viviparity vs both) in these extremely diverse taxa pose many challenges for the development of assisted reproductive technologies (ART). These include some species having large, yolky eggs which remain difficult to cryopreserve (Diwan et al. 2020), unique sperm storage capacities (Sever 2002), and extra-genomic control of sex differentiation (i.e. incubation temperature) (Nakamura 2009). Dr Simon Clulow (University of Canberra) described recent advances in both amphibian and reptile ART and the current state of genome resource banks for species conservation (Clulow and Clulow 2016; Bolton et al. 2022; Clulow et al. 2022). He highlighted that the utility of amphibian cryobank technology is stalled by our inability to successfully cryopreserve and subsequently thaw the large, yolky eggs or embryos of this taxa (Diwan et al. 2020). Currently, conventional cryoprotectants are only able to preserve amphibian spermatozoa and must later be combined with fresh eggs to generate sexually mature offspring (Upton et al. 2018, 2021), thus presenting a problem when a mature female of an endangered/extinct species is unavailable. Encouragingly, some success has been achieved in fish and coral egg and embryo cryopreservation, which are of similar sizes and yolk content to amphibians, by using conductive gold nano rods and ultra-rapid laser warming (Jin et al. 2014; Khosla et al. 2017). Although these technologies are still in their relative infancy, it is now proposed that they could be used to get around the egg and embryo freezing block in amphibian species (Clulow et al. 2022). Altogether, Dr Clulow showed that significant research is still required in this field to establish successful genomic bioresources for the conservation of these animals.

Another example of harnessing unique reproductive traits of animals for conservation efforts is demonstrated with the New Zealand kiwi. Current management systems, which all have varying degrees of success (Robertson et al. 2011), include predator control, kiwi translocation (movement of individuals from areas where they face extinction to protected areas), and projects such as ‘Operation Nest Egg’, wherein eggs and young chicks are cared for in captivity or predator-free habitats until they are large enough to survive in areas with predators (Colbourne et al. 2005). Professor Isabel Castro (Massey University) investigates kiwi breeding behaviours and explores how this knowledge might improve conservation efforts. Professor Castro determined that the brown kiwi has a mating system that includes monogamy and polygamy. Polygamy has genetic advantages over monogamy because it has the potential to alleviate inbreeding depression and encourages higher rates of gene flow. In fact, in a study population, individuals breeding together were more genetically dissimilar to each other than random birds selected from the population (Undin et al. 2021). Therefore, incorporation of polygamous strategies into current conservation programs may improve the genetic stability of kiwi populations and more closely mimic natural breeding strategies. Additionally, Professor Castro’s team discovered that egg incubation, which is primarily carried out by the male, may also be a major driver of kiwi mate selection and reproductive success. Interestingly, the 80-day process of egg incubation alters the hormonal profiles of the parental kiwis, which may have significant impacts on conservation strategies when eggs are translocated and the incubation process is disrupted (Jensen et al. 2019). Wild kiwi pairs divorce rates were found to be positively correlated to low male attentiveness at the nest (Ramos-Pallares, in preparation). In this regard, Operation Nest Egg, which sequesters eggs from wild nests into captivity for hatching may unintentionally identify the incubating males as undesirable mates in subsequent breeding rounds and indirectly remove their genetics from the population (Colbourne 2002). Ultimately, increased understanding of the reproductive biology of this remarkable avian species will increase the conservation program success.

Conservation strategies not only rely on enhancing breeding, but also on reducing the predation of vulnerable species. The unique Australian fauna and flora face major threats from invasive pests such as feral cats, rodents, rabbits, and foxes, all of which are responsible for costly biodiversity and agricultural production losses. To address this pressing issue, Dr Stephen Frankenberg and his team (University of Melbourne) are exploring ‘gene drive’ technology as a novel tool to manage invasive pest populations. Gene drive is a phenomenon when an allele is inherited by the offspring more than 50% of the time (Bier 2022). Dr Frankenberg hypothesised that by targeting genes that regulate female fertility (e.g. aromatase and progesterone receptor), suppression gene drives are a more effective and humane strategy to reduce/eradicate invasive species populations, particularly when compared to existing control methods which include baiting, trapping, and shooting. This work used a zebrafish model to optimise the design and subsequent efficiency of gene drive propagation through a population. Dr Frankenburg and his team are now developing pipelines to generate gene drive constructs which target non-model vertebrates including the European carp, cane toad, fox, and rabbit. This work is a perfect example of how exploiting and combining knowledge of both reproductive biology and genetic engineering could make a tremendous contribution to the conservation of our vulnerable fauna.

Another excellent example of this comes from the work of Dr Donna Bond (University of Otago). Dr Bond uses the invasive New Zealand Brushtail Possum (Trichosurus vulpecula) as a model to shed essential light on the reproductive strategies of these unique animals for two purposes. She aims to further efforts of possum pest control in New Zealand, which is currently a multimillion-dollar industry, and aid in conservation efforts for other Australian mainland marsupial species that are endangered. To address this, Dr Bond conducted nuclear and mitochondrial DNA analysis together with long-read methylation sequencing and identified allele/parent-specific methylation expression, not yet seen in other species. This novel insight challenges the expectation that marsupial imprinting is restricted to orthologues of mammalian imprinted genes such as in humans and mice and highlights the need for more species diversity in our analyses. These findings demonstrate that a ‘one-size fits all’ model does not always work across species, even closely related ones, and as such, may explain why conservation/eradication efforts remain ineffectual into the 21st century.

The intricacies of reproductive processes/strategies in exotic animal species including amphibians, reptiles, marsupials, and niche avian species (e.g. kiwi) have traditionally been understudied such that our understanding remains virtually unchanged since their initial discoveries. This has hindered conservation efforts and now presents a challenge as the list of species classified as vulnerable, endangered, or functionally extinct continues to grow annually according to the International Union for the Conservation of Nature’s Red List of Threatened Species. Fortunately, these recent research efforts are improving the fundamental understanding surrounding these unique species and are directly contributing to the protection, and where appropriate eradication, of species worldwide.

Speakers: Casey Spiller, John Schjenken, Timothy Hore, and Dagmar Wilhelm

This session explored recent updates in developmental biology, encompassing novel associations between endocrine-disrupting chemicals and retinoic acid (RA) signalling, the interplay between seminal fluid and the establishment of healthy pregnancies, the development of the androgen epigenetic clock and recent advances in ovarian development and function. A key theme of this session was the effects of environmental exposures, both exogenous and endogenous, on the homeostasis of the developing and adult gonads.

It is well established that the presence of RA, a derivative of vitamin A, is critical for the specification of mammalian gonads. Specifically, during fetal development, germ cells in the embryonic ovary initiate meiosis in response to the presence of RA, whereas those in the testis do not as they are shielded from this molecule (Endo et al. 2019). This ‘shielding’ occurs by virtue of an RA metabolising cytochrome P450 enzyme CYP26B1, a protein which is essential for testis development (MacLean et al. 2007). In situations where RA signalling is disrupted, gonadogenesis may also be disrupted, such that an ‘ovary/testis hybrid’ is produced akin to an intersex-like condition or congenital disorders of sex development (Bowles et al. 2018; Kam Draskau et al. 2022). Considering this, Dr Cassy Spiller (University of Queensland) is investigating the impact of RA signalling disruption by ectopic mechanisms. Specifically, her interest lies in how environmental exposures (i.e. endocrine-disrupting chemicals) might disrupt RA balance. Dr Spiller is exploring how common medicinal and agricultural antifungals (i.e. azoles), which are known to cross the placenta and have been found in embryos and fetal blood (Pilmis et al. 2015), affect early testicular development. These data will have profound implications for drug prescription during pregnancy as well as informing policy regarding safe exposure levels of known and suspected environmental endocrine-disrupting chemicals.

Associate Professor Dagmar Wilhelm (University of Melbourne) also discussed the importance of early ovarian development and how perturbations may significantly affect adult fertility (Smith et al. 2014). Dr Wilhelm has devoted her career to detailing the molecular events that drive sex determination, ovarian development, and disease. In a recent landmark publication, Dr Wilhelm and her collaborators detailed how the gonadal sexual fate determined during embryonic development, must be actively maintained in adulthood to prevent female-to-male sex reversal (Rossitto et al. 2022). Using a mouse model, they showed how in the ovary, estrogen receptors and Forkhead Box L2 (FOXL2) are responsible for protecting the ovarian granulosa cells from ‘transdifferentiation’ into Sertoli cells (Rossitto et al. 2022). Specifically, they show that recruitment of Tripartite Motif-Containing 28 (TRIM28) on chromatin in the proximity of FOXL2 acts to maintain the ovarian pathway and to repress testicular-specific genes preventing sex reversal of the mouse ovary after birth. Moreover, they show the role of TRIM28 in ovarian maintenance directly depends on E3-SUMO ligase activity which regulates the sex-specific SUMOylation profile of ovarian-specific genes. Altogether, these data indicate that TRIM28 is an important player in ovarian physiology and might therefore have a potential role in genetic diseases causing reproductive disorders. For instance, environmental factors, such as drugs or chemicals explored by Dr Spiller, interfered with the SUMO-E3-ligase activity of TRIM28, causing perturbed ovarian function and fertility. Understanding the underlying molecular regulation of gonadogenesis is thus highly relevant from a clinical perspective, as congenital disorders of sex development are not uncommon (Wilhelm et al. 2013).

In addition to exploring how environmental factors affect gametogenesis, this session also explored how they affect the establishment of a healthy pregnancy. Dr John Schjenken (University of Newcastle) highlighted the potential impact paternal environment stressors may have on seminal vesicle secretion and function. Seminal plasma is an acellular fluid mixture produced by the male accessory glands, particularly the seminal vesicles, in most mammalian species. Emerging evidence demonstrates that seminal plasma contributes to optimal fetal development and long-term offspring health (Bromfield et al. 2014; Watkins et al. 2018). The positive impact of signalling factors carried within seminal plasma, such as the transforming growth factor beta (TGFB) superfamily and cluster of differentiation 38 (CD38), on maternal immune tolerance is well-documented (Kim et al. 2015; Yang et al. 2021). What remains less known is the impact of paternal environment stressors on seminal vesicle quality and function. Dr Schjenken and his colleagues address this question using a variety of paternal environmental exposure models. In a paternal obesity model, Dr Schjenken showed a reduction in the expression of all three TGFB isoforms in seminal vesicle fluid from obese males (Schjenken et al. 2021). This observation likely explains the impairment of maternal immune tolerance (Schjenken et al. 2021) and the reduced implantation (Mitchell et al. 2011) rate previously reported in females mated with obese animals. Through proteome comparisons, Dr Schjenken and his colleagues also showed that seminal vesicle secretory functions are altered following acute acrylamide exposure, with more than 300 dysregulated proteins identified including serine protease inhibitors and seminal vesicle secretory proteins (Skerrett-Byrne et al. 2021). Collectively, these studies provide strong evidence that seminal vesicles respond to environmental exposures in a manner that may impact fertility, fetal development, and long-term offspring health, and thus further investigation into the underlying biology is warranted.

Epigenetic modifications are also key developmental regulatory pathways (Skinner 2011). For instance, measuring DNA methylation is a precise way of estimating the chronological age of an individual. In most mammals, this epigenetic clock is accelerated in males compared to females (Lemaître et al. 2020). Associate Professor Timothy Hore (University of Otago) and his team recently reported the first epigenetic clock for domesticated sheep, and found that the epigenetic clock and ageing are decelerated in castrated male sheep compared to intact sheep (Sugrue et al. 2021). They also identified regions in the genome that become hypomethylated with age in intact male sheep, including muskelin 1 (MKLN1), Ewing tumour-associated antigen 1 (ETAA1), and LIM domain transcription factor (LMO4). The methylation status of these regions in females and castrated males remain unchanged and are comparable over time, indicating these loci are sensitive to androgens (Sugrue et al. 2021). Similar reduction in methylation is also evident in male mice over time but in a tissue-specific manner depending on local androgen receptor expression (Sugrue et al. 2021), suggesting androgen-dependent DNA hypomethylation with age may exist in a wide range of mammalian species. Given the increased prevalence of androgen disorders such as polycystic ovarian syndrome (Yang et al. 2022), the findings from Associate Professor Hore and his group may lead to a tool that can measure androgen exposure and may have implications for reproductive disease diagnosis.

In summary, this session highlighted recent discoveries in developmental biology and, in particular, the significant impact environmental exposures have on fertility and development. Thus, further understanding of the interplay between developmental biology and environmental chemical exposure is crucial to lead to novel preventative and therapeutic interventions to improve fertility, health, and wellbeing in future generations.

Speakers: Diane Rebourcet, Zaramasina L. Clark, Cheow Yuen Tan, Lana McClements, Mark A. Baker, Zamira Gibb, and Shayanti Mukherjee

The 2022 SRB meeting had a strong focus on the ways fundamental science is being used to engineer creative solutions to safeguard and improve reproductive health in humans and other species. Across two symposia, ‘Fundamental Reproductive Engineering’ and ‘Applied Reproductive Engineering’, researchers highlighted how the application of foundational knowledge, and the engineering of novel techniques and tools, provides the capability to study the reproductive organs in greater detail, has the potential to revolutionise clinical practice and improve outcomes for reproductive health, and to improve reproductive efficiency in the context of agricultural and racing industries.

Steroid hormones play an important role in male reproduction and overall health. Alterations in steroid production or activity can lead to compromised sexual health, infertility, cardiovascular disease, and metabolic disorders (Gooren 2010; Rebourcet et al. 2014). The financial burden and unknown long-term efficacy of conventional hormone replacement therapies necessitates the development of safer and more efficient therapies, using new technologies. Dr Diane Rebourcet (University of Newcastle) and colleagues have developed a technology to target testicular cells in adult mice to provide a novel approach to regulating steroid production. Using a Hsd17b3 knockout mouse model that displays altered androgen production (Lawrence et al. 2022), Dr Rebourcet validated the effectiveness of lentiviral and adeno-associated virus 9 (AAV9)-mediated gene therapy in restoring classical androgen production. However, steroid production relies upon a pulsatile regulation from the hypothalamus–pituitary axis; therefore, to refine such approaches Dr Rebourcet has combined the fields of optogenetics and endocrinology. Optogenetics was initially developed as a tool to control neuronal activity by using specific wavelengths of light to manipulate and regulate gene transcription in a spatio-temporal manner (Emiliani et al. 2022). Extending on these studies, Dr Rebourcet is developing optogenetic tools to finely manipulate steroidogenic production in the mouse testis. She has transfected Leydig cell lines to overexpress a light-sensitive steroidogenic acute regulatory protein and finely control steroid production by using short bursts of light in vitro. These tools offer new possibilities for the development of therapeutic treatments to support endogenous androgen production and male health.

The gonadotrophic follicle-stimulating hormone (FSH) is routinely administered to women to improve the number of mature oocytes available for retrieval ahead of in vitro fertilisation (IVF) or embryo transfer. However, the dose of FSH is patient-dependent and high doses of FSH have been correlated with a decrease in live birth rate following IVF (Baker et al. 2015; Clark et al. 2021). Dr Zaramasina Clark (Michigan State University; Te Herenga Waka-Victoria University of Wellington) used the low ovarian reserve heifer model to better understand how high doses of FSH affect the cell types within the ovary. Heifers given an excessive (210IU Folltropin-V) dose of FSH showed high heterogeneity in the phenotypes of their cumulus-oocyte complexes (COCs). While a quarter of the COCs remained compact similar to the control lower (70 IU) FSH dose group, the remaining COCs showed variable levels of abnormality and premature development. RNA sequencing from high-dose FSH follicles identified progressive changes in oocytes, cumulus, and granulosa cell transcripts with increased levels of COC abnormality. Abnormal COCs predominantly displayed changes in pathways associated with follicular organisation, angiogenesis, and immune responses, but showed few changes in luteinisation pathways (Clark et al. 2022). Combined, these results suggest that the follicular microenvironment is disrupted, primarily due to the dysregulated differentiation of cumulus cells. This work defines how excessive FSH stimulation affects the follicular microenvironment, providing strong rationale to standardise FSH doses within an effective range in the clinic.

Intracytoplasmic sperm injection (ICSI) and vitrification are important ART routinely performed in clinical IVF. However, both procedures are technically challenging, requiring manual handling of oocytes by highly skilled embryologists and adherence to stringent time frames. The stress induced by these processes may lead to poor clinical outcomes (Shen et al. 2003; Tiegs and Scott 2020). Dr Tiffany Tan and colleagues (University of Adelaide) hypothesised that minimisation of oocyte handling will simplify both procedures and in turn, improve IVF outcomes. To address this, they designed and fabricated a micro-device to minimise oocyte handling during ICSI and vitrification. The device was fabricated by two-photon polymerisation and consists of two parts: the oocytes are held in the ‘pod’ and multiple pods can dock into a holding ‘garage’. This design circumvents the need for a holding pipette, thus minimising the manual handling of mouse oocytes during ICSI. Additionally, this pod and garage system minimises the volume of cryoprotectant needed at vitrification, as the oocyte is held within the device when moving across solutions with increasing concentrations of cryoprotectant. Importantly, compared to standard procedures, this device showed no differences in viability, developmental competency, or metabolism for oocytes and embryos in a mouse model. While future clinical trials are still needed, these data show this device has excellent potential to simplify the clinical procedures performed during ICSI and vitrification, and thus to provide patients with consistent outcomes for fertility treatment.

Preeclampsia is a multifactorial hypertensive disorder that affects 4–6% of all pregnancies (Chappell et al. 2021). In preeclampsia, the extravillous trophoblasts of the placenta fail to remodel the uterine blood vessels to sufficiently meet the energy demands of the growing fetus (McNally et al. 2017). Preeclampsia is challenging to examine and model, due to the lack of access to the placental tissue during pregnancy and the fact that the vast majority of other mammalian species do not spontaneously develop preeclampsia (Varas Enriquez et al. 2018). Associate Professor Lana McClements and her team (University of Technology Sydney) are developing new in vitro models of the placenta to decipher the mechanisms of preeclampsia and to test or validate potential treatment strategies. The first in vitro model prints a three-dimensional (3D) biofunctional hydrogel matrix containing a first trimester trophoblast cell line, which allows the differentiation of multiple subtypes of trophoblasts with different functions within the placental organoid. Next, Associate Professor McClements presented the ‘placenta-on-a-chip’ model, which combines first trimester trophoblast cells (ACH-3Ps) with human umbilical vein endothelial cells (HUVECs) within collagen in a microfluidic device. The trophoblast cells migrate towards the HUVECs in the middle channel of the device, forming a vascularised 3D placental model (Ghorbanpour et al. 2023). Combined, these models emulate the early placenta, allowing the differentiation of placental cell types, migration of trophoblast cells, and interactions with blood vessels. These functions make these models useful tools to understand placental biology and the molecular mechanisms of preeclampsia.

Male factor infertility affects a staggering 5–7% of men in the Western world, accounting for 50% of couples seeking ART (Kumar and Singh 2015). While ART procedures including IVF and ICSI have had widespread global success in helping sub- and infertile couples achieve pregnancy, these technologies are only able to treat the symptoms of infertility. The underlying causes, which may be propagated in future generations, remain a mystery in many cases. Associate Professor Mark Baker and his team (University of Newcastle) are focused on understanding the mechanisms of male factor infertility by using proteomic approaches. They have shown that the nuclear retention of specific proteins is common in poor quality sperm, and of note, despite the widely held dogma that male infertility is heterogenous in causality, they have shown across multiple donors that poor quality sperm are often characterised by nuclear retention of the same proteins (Netherton et al. 2020a). Proteomic elucidation of the transient effects of this nuclear protein retention has provided novel insight into the fundamental biology underpinning male reproductive health (Netherton et al. 2020b). The unbiased screening capacity of ‘omics’ approaches offer great potential for biomarker discovery research with translational potential for diagnosis and treatment of male infertility.

Proteomics are also utilised by Dr Zamira Gibb and her research team at the University of Newcastle to improve the breeding efficiency of agricultural stock and elite thoroughbred racehorses. Such racehorses have no ART alternatives to natural mating, making it imperative to maximise pregnancy rates each breeding season, where stallions are required to mate up to 200 mares over 12 weeks. Thus, a simple and accurate method of determining pregnancy probability from a single mating event is of great value to the industry. Proteomic analyses have revealed that horse spermatozoa utilise a different ATP production and energy avenue to humans (Gibb et al. 2014; Griffin et al. 2022) and such knowledge has led to the development of the Equility device which uses dismount semen samples to predict pregnancy outcome in the field (Clulow and Gibb 2022) and guided development of sperm storage media for use at ambient temperatures (Aitken et al. 2014). The Equility device provides a fluorescent reading proportional to mitochondrial oxidative phosphorylation, making this technology pivotal in breeder decision-making to remate pairs prior to the end of the breeding season where necessary.

Regenerative medicine is another area to benefit from the application of foundational reproductive biology. Technological advances in treating common conditions in obstetrics and gynaecology were discussed by Dr Shayanti Mukherjee (Hudson Institute of Medical Research) who emphasised the importance of understanding the practicality of technical devices and integrating this into the design process. Astonishingly, pelvic organ prolapse affects up to 50% of women following childbirth, yet lacks any effective treatment (Nygaard et al. 2008). Surgical intervention in the past has involved repair using a mesh implant; however, transvaginal mesh usage has been linked to severe surgical complications (Dällenbach 2015) and has been the subject of much controversy (Dyer 2016). Biomedical engineering has great potential for improving the success of pelvic reconstructive surgery; Dr Mukerjee’s team have made several advances in facilitating tissue repair with new nano-fabricated mesh materials (Paul et al. 2020) and endometrial stem cells (Mukherjee et al. 2020) to improve mesh integration into pelvic tissues. The combination of effective communication with key stakeholders and integration with pre-clinical models was highlighted as integral to successful translational research.

Collectively, these two symposia were a fitting reminder that bench-side breakthroughs can provide the groundwork for translational outcomes and for powerful new research tools. In particular, they illustrated the many ways in which practical application of advances in reproductive biology can benefit our society. Further, these sessions highlighted that engineering an effective product for translation requires a strong understanding of the target consumer, their needs and the unique challenges they face, and how the technology will be used. Efforts to address challenges in the areas of reproductive medicine, agriculture, and conservation will not only bring commercial rewards, but result in meaningful improvements to our understanding of reproductive biology.