The effect of heavy prenatal alcohol exposure on adolescent body mass index and waist-to-height ratio at 12-13 years.

BACKGROUND: Growing evidence suggests that prenatal alcohol exposure (PAE) has the potential to impact on a wide range of physical outcomes in offspring, including metabolism and body composition, although the evidence to-date is primarily from preclinical studies. The current clinical study examined the association between heavy PAE and indirect measures of adiposity in adolescence. METHODS: Analyses drew on data from the Longitudinal Study of Australian Children, a national prospective cohort of children and their families from birth to adolescence. Participants included children with heavy PAE (≥70 g/week; n = 46), measured via maternal self-report of alcohol use during pregnancy and a comparison group of children without any PAE (n = 782), frequency matched on sex, ethnicity and socio-economic position. Body mass index (BMI) z-scores, waist-to-height ratios and proportion overweight/obese were calculated from height, weight and waist circumference measured at age 12-13 years. Two (PAE) × two (sex) ANCOVA and logistic regression models were performed, controlling for matching variables, adolescent age, pubertal status and birthweight; maternal age at birth and smoking during pregnancy. RESULTS: Female adolescents with heavy PAE during late pregnancy had significantly higher BMI z-scores (M = 0.75, SD = 0.69) and proportion overweight/obese (38.5%) than females not exposed to any prenatal alcohol (M = 0.29, SD = 1.07, P = 0.04; 23.8%, P = 0.03, respectively). There was no significant effect of heavy PAE on male adolescent BMI z-scores and proportion overweight/obese or adolescent waist-to-height ratios (all P > 0.05). CONCLUSIONS: Heavy PAE had a sex-specific effect on measures of adiposity in early adolescence, with girls more likely to have increased BMI and overweight/obesity status. Further longitudinal follow-up of children exposed to PAE is required to confirm if maternal alcohol consumption is a risk factor for later life obesity.

Caregiver-reported physical health status of children and young people with fetal alcohol spectrum disorder.

While fetal alcohol spectrum disorder (FASD) has primarily been thought of as a neurodevelopmental condition, research is beginning to highlight its 'whole-body' implications. Accordingly, the current study sought to provide a snapshot of potential health issues. Caregivers of children (median age of 12 years) with an FASD diagnosis were invited to participate in an online survey. Information relating to sample demographics, FASD status of the child and health outcomes were collected. The prevalence of health conditions reported in the FASD sample was compared against national prevalence data. Multiple linear regression utilising a stepwise approach was used to investigate potential predictors of the number of diagnosed health conditions. Survey data were from an international cohort (n = 197), with the majority of respondents based in Australia (40.2%) or the United States (27.7%). The most commonly reported diagnosed health conditions were eye conditions (44.7%), asthma (34.5%), heart conditions (34.0%) and skin conditions (27.4%). Binomial testing indicated the proportion of children diagnosed with these disorders was generally higher in the current FASD population, compared to national prevalence data. Indicators of metabolic dysfunction including diabetes and obesity were not significantly different compared to national prevalence data. Age of FASD diagnosis, existence of comorbid mental health conditions and the primary caregiver being in paid work were identified as being associated with the prevalence of diagnosed health conditions. Overall, the study has provided an up-to-date snapshot of health problems reported in a sample of children with FASD, confirming their increased risk of adverse health outcomes.

Tissue-specific progesterone receptor-chromatin binding and the regulation of progesterone-dependent gene expression.

Progesterone receptor (PGR) co-ordinately regulates ovulation, fertilisation and embryo implantation through tissue-specific actions, but the mechanisms for divergent PGR action are poorly understood. Here we characterised PGR activity in mouse granulosa cells using combined ChIP-seq for PGR and H3K27ac and gene expression microarray. Comparison of granulosa, uterus and oviduct PGR-dependent genes showed almost complete tissue specificity in PGR target gene profiles. In granulosa cells 82% of identified PGR-regulated genes bound PGR within 3 kb of the gene and PGR binding sites were highly enriched in proximal promoter regions in close proximity to H3K27ac-modified active chromatin. Motif analysis showed highly enriched PGR binding to the PGR response element (GnACAnnnTGTnC), but PGR also interacted significantly with other transcription factor binding motifs. In uterus PGR showed far more tendency to bind intergenic chromatin regions and low evidence of interaction with other transcription factors. This is the first genome-wide description of PGR action in granulosa cells and systematic comparison of diverse PGR action in different reproductive tissues. It clarifies finely-tuned contextual PGR-chromatin interactions with implications for more targeted reproductive medicine.

Adverse reproductive outcomes associated with fetal alcohol exposure: a systematic review.

Fetal alcohol exposure results in well-characterised neurobehavioural deficits in offspring, which form the basis for diagnosing fetal alcohol spectrum disorder. However, there is increasing interest in the full range of health complications that can arise in children and adults with this disorder. We used a systematic review approach to locate all clinical and preclinical studies across a broad range of health outcomes in offspring exposed to prenatal alcohol. Our search encompassed four databases (PubMed, CINAHL, EMBASE and Web of Science) and titles/abstracts from retrieved studies were screened against strict inclusion/exclusion criteria. This review specifically evaluated studies reporting on reproductive outcomes in both males and females. A total of 23 studies were included, 5 clinical and 18 preclinical. Although there was a wide range in the quality of reporting across both clinical and preclinical studies, and variable results, trends emerged amongst the reproductive measures that were investigated. In females, most studies focussed on age at first menarche/puberty onset, with evidence for a significant delay in alcohol-exposed offspring. In males, offspring exposed to prenatal alcohol had altered testosterone levels, reduced testes and accessory gland weights and reduced sperm concentration and semen volume. However, further studies are required due to the paucity of clinical studies, the narrow scope of female reproductive outcomes examined and inconsistencies in outcomes across preclinical studies. We recommend that adolescents and individuals of reproductive age diagnosed with f-etal alcohol spectrum disorder be assessed for reproductive dysfunction to allow appropriate management of their reproductive health and fertility.

Recent and emerging reproductive biology research in Australia and New Zealand: highlights from the Society for Reproductive Biology Annual Meeting, 2017.

Research in reproductive science is essential to promote new developments in reproductive health and medicine, agriculture and conservation. The Society for Reproductive Biology (SRB) 2017 conference held in Perth (WA, Australia) provided a valuable update on current research programs in Australia and New Zealand. This conference review delivers a dedicated summary of significant questions, emerging concepts and innovative technologies presented in the symposia. This research demonstrates significant advances in the identification of precursors for a healthy pregnancy, birth and child, and discusses how these factors can influence disease risk. A key theme included preconception parental health and its effect on gametogenesis, embryo and fetal development and placental function. In addition, the perturbation of key developmental checkpoints was shown to contribute to a variety of pathological states that have the capacity to affect health and fertility. Importantly, the symposia discussed in this review emphasised the role of reproductive biology as a conduit for understanding the transmission of non-communicable diseases, such as metabolic disorders and cancers. The research presented at SRB 2017 has revealed key findings that have the prospect to change not only the fertility of the present generation, but also the health and reproductive capacity of future generations.

The current state of reproductive biology research in Australia and New Zealand: core themes from the Society for Reproductive Biology Annual Meeting, 2016.

Because reproduction is essential for all life, it is central to our understanding of all aspects of biology. The Society for Reproductive Biology (SRB) 2016 conference held on the Gold Coast (Qld, Australia) displayed the current breadth of reproductive research in Australia and New Zealand, with additional insights from world leaders in the field. This conference review provides a focused summary of the key questions, emerging ideas and novel technologies that were presented in the symposia. Presented research demonstrated key advances in how stem cell biology may allow us to better understand pluripotency, as well as how environmental and lifestyle factors, such as circadian disruption, smoking, alcohol and diet, affect gametogenesis, embryo implantation, placental function and reproductive capacity. Sessions also highlighted the role of reproductive biology in providing insight into the mechanisms and processes governing a wide range of biological science disciplines, including cancer research and therapies, oncofertility, conservation of native species and chronic non-communicable diseases. Recurring themes included the importance of male and female gamete quality for reproductive potential and the critical and varied roles of the placenta in the maintenance of a healthy pregnancy. Dysregulation of reproductive processes can contribute to a variety of pathological states that affect future health, fertility and fecundity. Research being conducted by the SRB has the potential to shape not only the fertility of the current generation, but also the health and reproductive viability of future generations.

Prenatal corticosterone exposure programs sex-specific adrenal adaptations in mouse offspring.

Maternal stress can impair foetal development and program sex-specific disease outcomes in offspring through the actions of maternally produced glucocorticoids, predominantly corticosterone (Cort) in rodents. We have demonstrated in mice that male but not female offspring prenatally exposed to Cort (33 µg/kg/h for 60 h beginning at E12.5) develop cardiovascular/renal dysfunction at 12 months. At 6 months of age, renal function was normal but male offspring had increased plasma aldosterone concentrations, suggesting that altered adrenal function may precede disease. This study investigated the long-term impact of prenatal exposure to Cort on adrenal growth, morphology and steroidogenic capacity as well as plasma Cort concentrations in offspring at postnatal day 30 (PN30), 6 months and 12 months of age. Prenatal Cort exposure decreased adrenal volume, particularly of the zona fasciculata, in male offspring at PN30 but increased both relative and absolute adrenal weight at 6 months of age. By 12 months of age, male Cort-exposed offspring had reduced absolute adrenal weight in association with increased adrenal plaque deposition (lipogenic pigmentation). Plasma Cort concentrations were elevated in male 6-month offspring but not at other ages. mRNA expression of Mc2r (ACTH receptor) was increased in males at PN30, and Cyp11a1 expression was decreased at 6 and 12 months of age. There were no changes in the adrenals of female Cort-exposed offspring. This study demonstrates that prenatal Cort exposure induces offspring adrenal gland dysfunction in an age- and sex-specific manner, which may contribute to long-term programmed disease in male offspring after maternal stress.

A review of fundamental principles for animal models of DOHaD research: an Australian perspective.

Epidemiology formed the basis of 'the Barker hypothesis', the concept of 'developmental programming' and today's discipline of the Developmental Origins of Health and Disease (DOHaD). Animal experimentation provided proof of the underlying concepts, and continues to generate knowledge of underlying mechanisms. Interventions in humans, based on DOHaD principles, will be informed by experiments in animals. As knowledge in this discipline has accumulated, from studies of humans and other animals, the complexity of interactions between genome, environment and epigenetics, has been revealed. The vast nature of programming stimuli and breadth of effects is becoming known. As a result of our accumulating knowledge we now appreciate the impact of many variables that contribute to programmed outcomes. To guide further animal research in this field, the Australia and New Zealand DOHaD society (ANZ DOHaD) Animals Models of DOHaD Research Working Group convened at the 2nd Annual ANZ DOHaD Congress in Melbourne, Australia in April 2015. This review summarizes the contributions of animal research to the understanding of DOHaD, and makes recommendations for the design and conduct of animal experiments to maximize relevance, reproducibility and translation of knowledge into improving health and well-being.

The critical roles of progesterone receptor (PGR) in ovulation, oocyte developmental competence and oviductal transport in mammalian reproduction.

Progesterone is critical for successful ovulation in the ovary and for the multi-faceted role of the oviduct in mammalian reproduction. Its effects are mediated by progesterone receptor (PGR), which is highly expressed in the ovary, specifically granulosa cells of preovulatory follicles in response to the luteinizing hormone (LH) surge that occurs just prior to ovulation, and in the oviduct, predominantly luminal epithelial cells but also muscle cells. This review will summarize research which shows that progesterone, via the actions of PGR, plays a key role in the functions of these cells and in the important periovulatory events of oocyte release, acquisition of oocyte developmental competence and oviductal transport of the newly formed embryo. PGR is a nuclear receptor that regulates the expression of many downstream target genes. However, although much is known about its expression characteristics in ovarian and oviductal cells, there is still much to unravel about the mechanisms by which PGR exerts its control over these important reproductive processes, particularly in the oviduct.