Progesterone regulation of endometrial factors supporting conceptus growth and development in the ovine uterus

Progesterone is unequivocally required for the establishment and maintenance of pregnancy in all mammals studied. Its known functions are complex and encompass global changes in gene expression. Therefore, studies were conducted to characterize the effects of progesterone on expression of genes for endometrial factors having roles in conceptus growth, implantation and establishment of pregnancy. The first study characterized the effect of an artificially induced early increase in circulating progesterone on conceptus growth and development and regulation of expression of galectin-15 (LGALS15), a recently identified protein secreted by the ovine uterine luminal epithelium (LE). Exogenous progesterone beginning on Day 1.5 post-mating accelerated conceptus development on Days 9 and 12. On Day 12 the conceptus was functionally and morphologically advanced to produce greater quantities of interferon tau (IFNT) than blastocysts from control ewes. Further, the endometrium responded to early progesterone and IFNT with early expression of cathepsin L (CTSL), radical S-adenosyl methionine domain containing 2 (RSAD2), and LGALS15 within the endometrium. The second study identifed structural changes within the luminal epithelium which could alter the flux of factors into and out of the uterine lumen to maintain appropriate fetal/maternal communication. In this study, progesterone reduced quantities of proteins associated with both tight and adherens junctions during the elongation period. IFNT subsequently increased these proteins after conceptus elongation. The third and fourth studies identified progesterone-regulated genes which have been implicated as having importance to implantation in sheep, mouse, and human. WNT signaling was transiently downregulated by progesterone, while members of several growth factor families are upregulated including insulin-like growth factor binding proteins (IGFBPs) 1 and 3, hepatocyte growth factor (HGF) and fibroblast growth factor 7 (FGF7), which may enhance conceptus growth. Collectively, these studies assess the role of progesterone in altering gene uterine expression to establish a favorable environment for conceptus development. The long-term goals of these studies are to establish biomarkers of receptivity to conceptus development and implantation, enhance our understanding of gene and pathway regulation in early pregnancy loss, and identify genes which may be targeted in therapeutic strategies to improve reproductive success in humans and animals

Evaluation of the effect of progesterone CIDR Devices on circulating levels of progesterone in cyclic ewes

A homogeneous group of thirty-one crossbred ewes was used to determine the effect of administering a progesterone Controlled Intravaginal Drug Releasing Device (CIDR) on circulating levels of progesterone in the subsequent cycle following CIDR removal. Circulating progesterone levels were determined for each ewe through daily blood collection via jugular venipuncture. Each ewe underwent a pretreatment 25 day sampling period (Period 1), a 12 day treatment period characterized by the presence of the CIDR (Period 2), and another 25 day sampling period following CIDR removal (Period 3). During the initial period of the study, progesterone levels in peripheral circulation changed (P < 0.0001, effect of day) in accordance with stage of the estrous cycle and were elevated during the luteal phase. In the second period of the study, progesterone levels were elevated (P < 0.0001) in ewes due to exogenous progesterone from the CIDR device (Period 1 versus Period 2: 1.3 ± 0.1 ng/ml versus 2.4 ± 0.1 ng/ml, respectively). After withdrawal of the CIDR in the third period of the study, circulating progesterone levels were not (P > 0.10) different from those observed in the initial period of the study (Period 1 versus Period 3: 1.3 ± 0.1 ng/ml versus 1.4 ± 0.1 ng/ml, respectively). Data collected in this study revealed that treatment with exogenous progesterone via CIDR for a 12- day treatment period does not influence circulating levels of progesterone in subsequent estrous cycles

Factors controlling nutrient availability to the developing fetus in ruminants

Inadequate delivery of nutrients results in intrauterine growth restriction (IUGR), which is a leading cause of neonatal morbidity and mortality in livestock. In ruminants, inadequate nutrition during pregnancy is often prevalent due to frequent utilization of exensive forage based grazing systems, making them highly susceptible to changes in nutrient quality and availability. Delivery of nutrients to the fetus is dependent on a number of critical factors including placental growth and development, utero-placental blood flow, nutrient availability, and placental metabolism and transport capacity. Previous findings from our laboratory and others, highlight essential roles for amino acids and their metabolites in supporting normal fetal growth and development, as well as the critical role for amino acid transporters in nutrient delivery to the fetus. The focus of this review will be on the role of maternal nutrition on placental form and function as a regulator of fetal development in ruminants

Study protocol: a pragmatic randomised controlled trial of a 12-week physical activity and nutritional education program for overweight Aboriginal and Torres Strait Islander women

<p>Abstract</p> <p>Background</p> <p>Aboriginal and Torres Strait Islander women have a higher prevalence and incidence of obesity and type 2 diabetes than non-Indigenous Australian women. Physical inactivity is a key modifiable risk factor for obesity and evidence shows that even modest reductions in waist circumference (WC) have significant health benefits. Trialing physical activity programs in difficult-to-reach high risk groups, especially urban Indigenous Australians poses distinct implementation challenges.</p> <p>Methods/Design</p> <p>The trial objective is to evaluate the effectiveness of a structured 12-week physical activity group program with nutritional advice. The design is a pragmatic randomised controlled trial. This study protocol describes the implementation and evaluation of the program. Participants are randomised into either an intervention or waitlisted group. The waitlisted group have a 12 month waiting period before commencing the 12-week program. Participant data is collected at baseline, 12, 24 and 52 weeks. Participants are Aboriginal and Torres Strait Islander women, aged 18-64 years with a waist circumference greater than 80 centimetres residing in Adelaide. The primary outcome measure is WC change immediately post program from baseline. Secondary outcomes include short term and long term changes in WC, weight, blood pressure, fasting blood glucose, insulin, insulin resistance (calculated HOMA), haemoglobin A1C (HbA1C), triglycerides and C-reactive protein (CRP). Behavioural and psychosocial surveys are administered to assess physical activity, dietary intake and the participant's motivation, self-efficacy and perceived social support for physical activity. Qualitative interviews focusing on participants' motivation, enablers and barriers to healthy eating and physical activity will be undertaken. Implementation fidelity and participation are also assessed.</p> <p>Discussion</p> <p>The Aboriginal and Torres Strait Islander Women's Fitness Program (WFP) is designed to provide a rigorous physiological and client-based evaluation of a structured 12-week program aimed to increase metabolic fitness and reduce WC in this high risk population. Evaluation results aim to provide the support necessary to design programs that are accessible, affordable and effective at reducing WC, while also improving the metabolic profile of overweight Aboriginal and Torres Strait Islander women.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Registry <a href="http://www.anzctr.org.au/ACTRN12610000224022.aspx">ACTRN12610000224022</a></p

Functional roles of agmatinase during the peri-implantation period of pregnancy in sheep

This study investigated the effect of agmatine (Agm) in proliferation of ovine trophecdoderm cells (oTr1) as well as the importance of the arginine decarboxylase (ADC) and agmatinase (AGMAT) alternative pathway for synthesis of polyamines in ovine conceptuses during the peri-implantation period of pregnancy. Morpholino antisense oligonucleotides (MAOs) were used to inhibit translation of mRNAs for ODC1 alone, AGMAT alone, and their combination. Rambouillet ewes (N = 50) were assigned randomly to the following treatments on Day 8 of pregnancy: MAO control (n = 10); MAO-ODC1 (n = 8); MAO-ADC (n = 6); MAO-ODC1:MAO-ADC (n = 9); or MAO-ODC1:MAO-AGMAT (n = 9). Ewes were ovario-hysterectomized on Day 16 of pregnancy to obtain uterine flushings, uterine endometrium, and conceptus tissues. Inhibition of translation of both ODC1 and AGMAT resulted in 22% of ewes having morphologically and functionally normal (elongated and healthy) conceptuses designated MAO-ODC1:MAO-AGMAT (A). But, 78% of the MAO-ODC1:MAO-AGMAT ewes had morphologically and functionally abnormal (not elongated and fragmented) conceptuses designated MAO-ODC1:MAO-AGMAT (B). The pregnancy rate was less (22%; P < 0.05) for MAO-ODC1:MAO-AGMAT ewes than for MAO-control (80%), MAO-ODC1 (75%), MAO-ADC (84%), and MAO-ODC1:MAO-ADC (44%) ewes. Moreover, inhibition of translational of both ODC1 and AGMAT mRNAs increased expression of ADC, SLC22A1, SLC22A2, and SLC22A3 mRNAs, as well as abundances of agmatine, putrescine, spermindine, and spermine in conceptus tissue. However, MAO-ODC1:AGMAT(B) ewes had greater abundances of agmatine, putrescine, and spermidine and reduced amounts of spermine in uterine flushes. Thus, in vivo knockdown of translation of ODC1 and AGMAT mRNAs increased expression of genes for the synthesis and transport of polyamines in ovine conceptuses during the peri-implantation period of pregnancy