Latest Articles

The benefits of ‘good’ cholesterol in reproduction: how high-density lipoproteins help to prepare sperm for fertilisation in breeding rams

The use of assisted reproductive technologies—such as artificial insemination (AI) or in vitro fertilisation (IVF)—has revolutionised breeding in livestock industries. Assisted reproductive technologies can improve both the quality and reproductive potential of the herd, leading to an increase in overall production efficiency. Improvements in the application of these technologies to the sheep industry is reliant on a greater understanding of the physiology of fertilisation in this species. In particular, there is a need to better understand the process of sperm capacitation—a maturation event that prepares sperm for fertilisation—in the ram.

In a recent study, researchers at the University of Sydney and Utrecht University examined the effectiveness of different media components to support capacitation-related processes in ram sperm. They focussed on a particular aspect of sperm capacitation known as cholesterol efflux, where cholesterol is removed from the sperm plasma membrane. High-density lipoproteins (HDLs) were investigated for their potential to remove cholesterol from the ram sperm membrane during capacitation. HDLs, known as the ‘good’ cholesterol, are known to promote cholesterol efflux in other cells, including sperm in different species, and have been identified in fluids derived from the female reproductive tract.

The researchers found that cholesterol efflux was indeed stimulated in ram sperm exposed to HDLs during capacitation and at a rate that was similar to bovine serum albumin (BSA), which is traditionally used to support this process. Remarkably, HDLs, unlike BSA, also stimulated an increase in sperm tail movement, otherwise known as hyperactivation. This change in tail movement propels sperm to the site of fertilisation and is required to penetrate and fertilise the oocyte (egg). Therefore, HDLs supported multiple sperm functions that are important for successful fertilisation.

This exciting research suggests HDL supplementation to media used for sperm capacitation could improve the capacity for fertilisation in ram sperm, and as a result, could potentially be used in IVF systems for breeding herds.

Written by Naomi Bernecic

Rodent, primate, or something in between…? How the Egyptian spiny mouse may be a new animal model for human pregnancy

The study of disorders of pregnancy and menstruation has been hampered by the fact that most commonly used laboratory animal models, such as mice, don’t menstruate. In fact, menstruation is incredibly rare in nature and is largely restricted to higher-order primates such as gorillas, orang-utans and humans; a mere 1.5% of the 5,502 known mammalian species.

The study of disorders of pregnancy and menstruation has been hampered by the fact that most commonly used laboratory animal models, such as mice, don’t menstruate. In fact, menstruation is incredibly rare in nature and is largely restricted to higher-order primates such as gorillas, orang-utans and humans; a mere 1.5% of the 5,502 known mammalian species.

However, researchers at Monash University and Hudson Institute of Medical Research discovered that a tiny rodent known as the Egyptian spiny mouse (Acomys cahirinus) exhibits cyclical, human-like menstruation. This discovery, published in 2017, represented a game-changing breakthrough for studying female reproductive health. The team has now published new research providing more detail about early pregnancy in this fascinating species.

The team showed some fascinating similarities and differences to humans in terms of ovulation and embryo implantation. They showed that spiny mice are capable of ovulating and getting pregnant soon after they have given birth and when they are lactating. This is unlike the situation in humans where breastfeeding prevents ovulation for around 6 months. Spiny mouse embryos also don’t embed as deeply in the uterine endometrium, suggesting they may not experience the same hormonal control of ovulation and embryo implantation seen in humans.

Surprisingly though, spiny mouse early pregnancy involves the formation and remodelling of endometrial spiral arteries that are observed in menstrual species such as humans. These coiled, spring-like arteries act as shock absorbers for the growing embryo and directly provide the placenta with blood flow. Inadequate formation or remodelling of these arteries can lead to major pregnancy complications such as preeclampsia or intrauterine growth restriction (IUGR). The spiny mouse model could be used to give unique insights into how these arteries form and how their dysfunction could lead to pregnancy complications.

Overall, the research revealed that spiny mice appear to be a ‘pick and mix’ of reproductive characteristics from both rodents and primates, and that spiny mice undergo similar uterine remodelling around the time of embryo implantation as menstruating species. The authors hope this study will guide future studies in this species to provide new insights into pathologies and treatment options for pregnancy disorders such as IUGR and preeclampsia.

Written by Jarrod McKenna and Liza O’Donnell

Sperm proteins on the wrong side of the fence: implications for the diagnosis and treatment of male infertility……and cancer

Our immune systems develop after birth to recognise and attack foreign proteins but also to learn which proteins are normally present inside our body. When a boy goes through puberty however, sperm start to develop for the first time within his testes, meaning that proteins specifically found in sperm are at risk of being recognised as foreign by the immune system. Scientists have long assumed that these proteins must be restricted inside a “fence” within the sperm-producing tubules of the testis so they can’t be attacked by immune cells or enter the circulation.

Yet surprising new research led by scientists at the Hudson Institute of Medical Research, University of Newcastle and Walter and Eliza Hall Institute shows that many sperm-specific proteins are normally released by the tubules. Once released, they are freely able to interact with the immune system and to enter the circulation. The researchers believe the tubules release these proteins to “tolerise” the immune system; to signal that the proteins are not foreign and help prevent a major immune response if the testis is compromised.

This unexpected finding goes against what is currently known about testis biology, but also has two important implications.

First, the fact that these sperm-specific proteins are released from the tubules and can enter the circulation opens up the possibility of developing a blood test to diagnose fertility and testis function. Almost 10% of infertile men have no sperm in their ejaculate but may have sperm in their testes that could be retrieved surgically and used in IVF. However up to half of these men will have no sperm to be retrieved in their testes, and will thus undergo surgery unnecessarily. This new research shows it is possible to design a blood test to see which men have sperm in their testes. This blood test could be used to better diagnose and rationalise treatment for men with various types of infertility.

Second, the findings also have surprising implications for designing new diagnoses and treatments for cancer. Many cancers express proteins called cancer-testis antigens (CTAs). These are proteins thought to only be expressed in developing sperm and not found elsewhere in the body, but are abnormally produced by certain cancers. Because CTAs are assumed to remain within the testis tubules and to be absent from the circulation in a healthy man, researchers have assumed they would be excellent cancer biomarkers because they should only be detected when they are produced by a cancer. They are also assumed to be excellent targets for cancer immunotherapy because they should generate a strong immune response that could be harnessed to kill cancer cells. However, the new research showed some CTAs are released normally by the tubules in men, suggesting that the immune system may be tolerant to them, and also suggesting they could appear in the circulation of healthy men. This research provides essential information to guide scientists about which CTAs would be the best targets for cancer diagnosis and immunotherapy, and which are less likely to be effective.

New research paves the way for designing dietary interventions to treat infertility in women with PCOS

Polycystic Ovary Syndrome (PCOS) is the most commonly diagnosed endocrine disorder in women and is characterised by high blood levels of androgens (such as testosterone), irregular menstrual cycles and abnormal changes in the ovary. Women with PCOS are also at a higher risk of developing obesity, metabolic syndrome, type II diabetes and depression and of suffering from infertility. Researchers have postulated that dietary interventions could be an attractive option to improve the symptoms of PCOS as they would be minimally invasive, cost effective and provide a wide range of health benefits. However it can be difficult to identify the best dietary interventions as human studies can be challenging due to variability between individuals and the cost of performing large studies.

An important new study, led by Valentina Rodriguez Paris and Kirsty Walters and a team of researchers from the University of New South Wales, Charles Perkin Centre and the ANZAC Research Institute, used a new approach to examine whether, and how, the severity of PCOS is driven by macronutrient intake, i.e. diet.

The researchers used a mouse model of PCOS caused by high levels of androgens that replicates traits found in women with PCOS. By feeding normal and PCOS mice very specific combinations of carbohydrate, fat and protein, the researchers were able to study how changes in diet influence female metabolism, reproduction and physiology.

Female PCOS mice gained weight, as is observed in women, however this was not due to higher calorie intake, eating habits, food preference or activity levels, indicating that the high androgen levels in PCOS influences body weight and metabolism. Importantly, the study found a very specific diet fed to PCOS mice caused them to ovulate and resume their estrous cycle. This diet followed key principles of the Mediterranean diet that is well known to promote a wide array of health benefits.

This exciting research suggests that women with PCOS could potentially improve their fertility by following a Mediterranean-style diet. This new data is important to direct future studies on the specific dietary interventions that could improve fertility in women with PCOS.

Read the article

Written by Drs Macarena Gonzalez and Liza O’Donnell

Ensuring prospective patients have access to the information they need to make informed decisions

The use of assisted reproductive technology (ART) is now commonplace in Australia, helping couples and singles achieve their goal of starting a family. Women can now also use these services to safeguard against future infertility by freezing their eggs and thus potentially avoiding a major cause of infertility – age.  

Many fertility clinics that offer egg freezing have been established across the country, yet choosing the right clinic can be difficult for women, and often the first place they acquire information is online. Providing high quality information online is important as it informs a patient’s choice of clinic before further interaction with a fertility specialist. The fertility industry is now highly competitive, with clinics using online media to attract prospective customers. However the quality of the information available online does not always allow prospective patients to make an informed choice regarding their treatment options.

Researchers at Monash University have published a study evaluating the quality of information that prospective users can access online. This work, featured in The Sydney Morning Herald, found that the majority of clinics scored either a ‘poor’ or ‘moderate’ score when evaluated using a tool that was initially developed to audit the US market. Areas that most commonly lacked transparency included success rates, how age and egg freezing impacted these success rates, and the cost of treatment.

The authors call attention to the need for patients to be better informed before they embark on egg freezing for fertility preservation. In particular, the authors highlight that it is essential that women considering whether to undergo egg freezing have access to the information they need to make an informed choice – and that they clearly understand the high costs, potential health risks and success rates, particularly in relation to age.

The authors hope the study will lead to improvements in the way egg freezing is presented to prospective customers, and will provide clinics with a guide as to what information is important for patients to make informed decisions.  

Written by Drs Kiri Beilby and Liza O’Donnell

Australian researchers discover a novel cause of preeclampsia

Preeclampsia is a life-threatening, pregnancy-induced disorder unique to humans. It is diagnosed by the sudden onset of maternal hypertension after 20 weeks of pregnancy plus one other symptom including elevated urinary protein, other organ damage or fetal growth restriction. If left unmanaged, preeclampsia can lead to maternal seizures (eclampsia) and death. Preeclampsia affects between 3-4% of all pregnancies in Australia, with 10,000 women diagnosed in Australia each year.

This dangerous condition is caused by a damaged placenta which releases toxins into the maternal blood stream, causing the clinical symptoms. It is widely accepted that preeclampsia arises due to abnormal placental development during the early stages of pregnancy however studying human placental development is very difficult and the mechanisms leading to poor placental development remain unclear.

New research published in Hypertension by Dr Ellen Menkhorst and Professor Eva Dimitriadis from the University of Melbourne and the Royal Women’s Hospital, has identified that a protein called galectin-7 is abnormally elevated in the early pregnancy placenta of women who subsequently develop preterm preeclampsia. The researchers were able to show that elevations of this protein in mice caused classic symptoms of preeclampsia, including hypertension and elevated urinary protein. Galectin-7 was also shown to regulate key components of the renin-angiotensin system, a central hormone system controlling blood pressure.

Overall this new research suggests that elevated placental production of galectin-7 during early pregnancy contributes to abnormal placental development and altered renin-angiotensin system function which may ultimately lead to the development of preeclampsia. 

The researchers hope this discovery will lead to the identification of new treatment options to improve placental development during early pregnancy and prevent preeclampsia.

Written by Drs Ellen Menkhorst and Liza O’Donnell

Researchers propose a new concept for the cause of premature menopause

On average, women undergo menopause at the age of 51. However, early menopause ,which can occur between the ages of 40 and 45, and in some cases before the age of 40, has been associated with environmental exposures and genetic causes.

Previous research into the genetics of early menopause suggested that errors in genes for genome maintenance and DNA repair could be involved. Other research has proposed that an increased rate of death of ovarian follicles can deplete the reserve of follicles, thus causing early menopause.

An article in Human Reproduction by Dr Ray Rodgers at the Robinson Research Institute and Dr Joop Laven from Erasmus University Rotterdam proposes a new mechanism by which genetic changes in a specific region of the ovary could lead to follicle death. The researchers propose a link between genetic changes known to be associated with premature menopause, and those known to be involved in follicle degeneration (atresia). These findings support the concept that more follicles are likely to die in women who have less effective genes for genome maintenance. This in turn could lead to an earlier depletion in follicle reserves and ultimately to early menopause.

This new concept of follicle depletion will direct research that could ultimately lead to the development of novel strategies to prevent follicle depletion and early menopause.

Find the article here

Written by Antoinette Lam and Liza O’Donnell

Highlighting the impacts of pollution on wildlife reproduction

The environment is changing at an unprecedented rate due to human activity. Wildlife are increasingly confronted with many forms of anthropogenic pollution, including chemicals released through the usage and disposal of countless products, noise from traffic and industrial activities, artificial light at night, and heat pollution from urban heat islands and global warming. These various forms of pollution can disrupt many biological processes that are critical for successful reproduction.

A recent review led by Australian researchers highlights the scope of disruption of reproductive processes via a diverse range of pollutants. This includes not only direct effects on the physiology and development of reproductive organs, but also consequences on factors relevant to reproduction such as shifts in reproductive timing, impacts on gamete quality, and interference of sexual communication and selection. The authors highlight how these alterations to traits necessary for reproductive success can have detrimental repercussions on populations and wider ecosystems, as well as ramifications on the evolution of affected species. The authors then suggest a number of strategies that could be implemented to mitigate the concerning impacts of pollution, such as additional wastewater treatment steps, sound barriers, and reduced usage of artificial light.

Read the review article here

Written by Lucinda Aulsebrook and Liza O’Donnell

Australian researchers show a commonly used herbicide in Australia affects reproductive development in wallabies

Marsupials are experiencing devastating population declines across Australia, with 21 per cent of native mammals currently threatened with extinction. As their habitat becomes more restricted, marsupials are pushed into agricultural areas and forestry plantations, attracted to the food resources and rare permanent water sources.  This shift may increase their risk of exposure to agricultural contaminants, such as pesticides.

The herbicide atrazine is of particular concern due to its ability to disrupt the signals from reproductive hormones in a broad range of vertebrates, including fish, reptiles, frogs and rodents. Atrazine is of such concern that it has been banned across the European Union since 2003, due to its known impacts on the health of wildlife and potential impacts on humans.  However atrazine is used extensively in Australia, on cereal crops and in forestation to prevent the growth of weeds, with approximately 3000 tons used on crops annually.

Researchers at the University of Melbourne investigated whether atrazine disrupted development of the reproductive organs in marsupials. After exposure to atrazine at 450ppm in the drinking water during gestation and lactation, male offspring had a 20% reduction in penis length and altered expression of genes involved in testis development. This indicates that the hormone environment had been disrupted during a critical window of reproductive development.

This is the first study to show that endocrine disruptors (chemicals that disrupt normal hormone signalling) are able to affect developing marsupial pouch young through gestational and lactational exposure. These data raise major concerns for the use of pesticides in areas with vulnerable or endangered marsupial populations and illustrates the need for more stringent guidelines surrounding the use of known endocrine disrupting chemicals such as atrazine in Australia.

Read more here

Written by Laura Cook and Liza O’Donnell

New study investigates how ovarian development in the fetus could be linked to the development of Polycystic Ovary Syndrome (PCOS) later in life

Polycystic ovary syndrome (PCOS) is a common reproductive metabolic disorder of unknown cause(s). A person’s genes and history of development as a fetus both seem to affect the development of PCOS in later life, but how this happens is not known.

Researchers at the Robinson Research Institute in Adelaide formed a collaboration with international researchers to investigate whether genes known to be involved in PCOS are active during development of the foetal ovary. The research found that nearly all of the PCOS genes were activated during ovarian development and they clustered into three different patterns of activity, probably indicating different important roles in development.

These results are important because they provide clues as to the processes in fetal ovarian development that could be linked to PCOS later in life. The next step is to discover the factors that alter these genes during foetal development and to use this knowledge to identify strategies to prevent PCOS.

Read more here