2. Universidad Cardenal Herrera-CEU

During pregnancy, women undergo several metabolic changes to guarantee an adequate supply of glucose to the foetus. These metabolic modifications develop what is known as physiological insulin resistance. When this process is altered, however, gestational diabetes mellitus (GDM) occurs. GDM is a multifactorial disease, and genetic and environmental factors play a crucial role in its aetiopathogenesis. GDM has been linked to both macroscopic and molecular alterations in placental tissues that affect placental physiology. This review summarizes the role of the placenta in the development of GDM from a molecular perspective, including hormonal and pro- inflammatory changes. Inflammation and hormonal imbalance, the characteristics dominating the GDM microenvironment, are responsible for placental changes in size and vascularity, leading to dysregulation in maternal and foetal circulations and to complications in the newborn. In conclusion, since the hormonal mechanisms operating in GDM have not been fully elucidated, more research should be done to improve the quality of life of patients with GDM and their future children.

Propósito/Contexto. En este artículo queremos evidenciar la existencia de la invisibilización médica y social producida en torno a las pérdidas embriofetales en madres gestantes. Metodología/Enfoque. Se hace una revisión bibliográfica de carácter narrativo y bioético de publicaciones que analizan específicamente cómo afecta a las madres gestantes el modo de comunicar del personal de salud cuando han de notificar la pérdida de su hijo por complicaciones en el desarrollo embriofetal. Revisamos si en esa comunicación se aplican los principios de la Bioética. Resultados/Hallazgos. Tras el análisis realizado encontramos que, con frecuencia, las madres gestantes que sufren esos abortos naturales, a menudo, experimentan una ausencia de empatía y humanidad en los profesionales de la salud que no cubren adecuadamente –éticamente– la magnitud que supone esa pérdida del hijo en desarrollo. Añadimos que esta situación se agrava por el sentimiento de fracaso y soledad, unido a la tristeza y el duelo por el que transitan. Discusión/Conclusiones/Contribuciones. Realzamos el valor ontológico y humano que le otorgan las madres a la muerte del que consideran su hijo, independientemente del momento del desarrollo en el que se encuentre. La muerte imprevista en las primeras semanas del embarazo no debería quedar reducida a un accidente meramente fisiológico y sin importancia a nivel comunicativo. Concluimos que es necesario asesorar a los profesionales de salud a través de protocolos médicos y éticos que les permitan abordar el cuidado de aquellos pacientes que atraviesan esta situación de perdida embriofetal. Consideramos desde la bioética que, ante estas críticas circunstancias, debería priorizarse el principio de beneficencia, habida cuenta de que una mala comunicación afecta negativamente al bienestar físico y psíquico de estas pacientes.

Two experiments were conducted in the Northern (UK) and Southern (Brazil) hemispheres to determine the effect of season (month of conception) on the development of supplementary CL (SCL) and the relationship with pregnancy loss. In experiment 1, 199 pregnancies were followed between Day 14 and term, to determine the number of SCL and pregnancy viability (Northern Hemisphere). From the 199 pregnancies, 178 were obtained from inseminations during the breeding season (March–September), while the rest, 21 pregnancies resulted from conceptions in the non-breeding season (October to February). Pregnancies conceived in the breeding season were more likely (P < 0.01) to have at least 1 SCL (75.8 %, 135/178) than pregnancies from the non-breeding season (33 %, 7/21). However, the pregnancy loss between Days 35 and 120 of pregnancy in mares with no SCL was similar (3.5 %, 2/57; P >0.1) than from mares with SCL (1.4 %, 2/142). In Experiment 2 (Southern Hemisphere), three groups of recipients were used based on their ovarian activity at the time of embryo transfer: Anestrus (n = 8), transitional (n = 7) and cyclic (n = 7) recipient mares. While all transitional and cyclic mares developed at least 1 SCL, only 50 % of anestrous recipients (4/8) developed SCL by 120 of gestation. In conclusion, the development of SCL in pregnant mares is influenced by the time of season of conception, therefore it appears to be regulated by the photoperiod and the endogenous seasonal variation in gonadotropin concentrations. Mares with no SCL were not at increased risk of pregnancy loss.

During pregnancy, maternal erythropoietic expansion and fetal development require greater mobilization of available iron (Fe) stores. These adjustments in Fe metabolism in humans and rodents are largely mediated by the hormone hepcidin (Hepc), which controls the expression of ferroportin (Fpn), a transporter responsible for exporting Fe from stores to extracellular fluid and plasma. These mechanisms based on the regulation of Hepc on the availability of Fe during gestation in healthy mares remain unknown. The objective of this study was to determine the existence of interrelationships among concentrations of Hepc, ferritin (Ferr), Fe, and estrone (E1) and progesterone (P4) in Spanish Purebred mares along the whole gestation. Blood samples were taken from 31 Spanish Purebred mares each month, during 11 months of pregnancy. Fe and Ferr significantly increased and Hepc decreased during pregnancy (P < 0.05). The secretion peak of estrone (E1) was reached in the 5th month and progesterone (P4) between the 2nd and 3rd months of gestation (P < 0.05). Fe and Ferr were weakly positively correlated (r = 0.57; P < 0.05). Fe and Ferr were negatively correlated with Hepc (r = −0.80 and r = −0.67, respectively) (P < 0.05). P4 was positively correlated with Hepc (r = 0.53; P < 0.05). Pregnancy in the Spanish Purebred mare was characterized by a progressive increase in Fe and Ferr and a reduction in Hepc concentrations. E1 was partially responsible for the suppression of Hepc; on the other hand, P4 induced its stimulation during pregnancy in the mare.

In woman and in animal models, estrogens are involved in iron (Fe) homeostasis supporting the hypothesis of the existence of an “estrogen-iron axis”. Since advancing age leads to a decrease in estrogen levels, the mechanisms of Fe regulation could be compromised. In cyclic and pregnant mares, to date, there is evidence linking the iron state with estrogens pattern. Then, the objective of this study was to determine the relationship among Fe, ferritin (Ferr), hepcidin (Hepc) and estradiol-17β (E2) in cyclic mares with advancing age. A total of 40 Spanish Purebred mares of different ranges of age was analyzed: 4–6 years (n = 10), 7–9 years (n = 10), 10–12 years (n = 10), and >12 years (n = 10). Blood samples were obtained on days −5, 0, +5 and + 16 of the cycle. Compared to mares of 4–6 years, serum Ferr was significantly higher (P < 0.01) and Fe significantly lower (P < 0.01) in mares >12 years of age. Hepc was significantly higher in mares >12 years (P < 0.01) than in those 7–9 years of age. E2 levels were higher in mares of 7–9 years (P < 0.01) than in 4–6 and >12 years of age. Fe and Ferr were negatively correlated with Hepc (r = −0.71 and r = −0.02, respectively). E2 was negatively correlated with Ferr and Hepc (r = −0.28 and r = −0.50, respectively), and positively with Fe (r = 0.31). There is a direct relationship between E2 and Fe metabolism, mediated by the inhibition of Hepc in Spanish Purebred mares. The reduction of E2 decreases the inhibitory effects on Hepc, increasing the levels of stored Fe and mobilizing less the free Fe in circulation. Based on the fact that ovarian estrogens participate in changes in the parameters indicative of iron status with age, the existence of an “estrogen-iron axis” in the mares'estrous cycle could be considered. Future studies are required to clarify these hormonal and metabolic interrelationships in the mare.

Ecological nutrition aims to unravel the extensive web of nutritional links that drives animals in their interactions with their ecological environments. Nutrition plays a key role in the success of European wild rabbit (Oryctolagus cuniculus) and could be affected by the breeding status of the animals and reflected in the metabolome of this species. As nutritional needs are considerably increased during pregnancy and lactation, the main objective of this work was to determine how the breeding status (pregnant and lactating) of European wild rabbit does affects nutritional requirements and their metabolome (using targeted and untargeted metabolomics), aiming to find a useful biomarker of breeding status and for monitoring nutritional requirements. To address this gap, 60 wild European rabbits were studied. Animals were divided according to their breeding status and only pregnant (n = 18) and lactating (n = 11) rabbit does were used (n = 29 in total). The body weight and length of each animal were analyzed. The relative and absolute chemical composition of the gastric content and whole blood sample were taken, and targeted and untargeted metabolomics were analyzed. As a main result, there were no differences in biometric measurements, gastric content, and targeted metabolomics, except for live weight and nonesterified fatty acids (NEFA), as pregnant animals showed higher live weight (+12%; p = 0.0234) and lower NEFA acid levels (−46%; p = 0.0262) than lactating females. Regarding untargeted metabolomics, a good differentiation of the metabolome of the two breeding groups was confirmed, and it was proven that pregnant animals showed higher plasmatic levels of succinic anhydride (3.48 more times; p = 0.0236), succinic acid (succinate) (3.1 more times; p = 0.0068) and propionic acid (3.98 more times; p = 0.0121) than lactating animals. However, lactating animals showed higher levels of N-[(3a,5b,7b)-7-hydroxy-24-oxo-3-(sulfoxide) cholan-24-yl]-Glycine (cholestadien) (2.4 more times; p < 0.0420), 4-maleyl-acetoacetate (MAA) (3.2 more times; p < 0.0364) and irilone (2.2 more times; p = 0.0451) than pregnant animals, any of these metabolites could be used as a potential biomarker. From these results, it can be concluded that the most notable changes were observed in the metabolome of individuals, with most of the changes observed being due to energy and protein mobilisation.

Background: PGF2α is commonly given at the end of embryo flushing (EF) to shorten the interval to the next oestrus and ovulation. Objectives: To determine the effect of repeated EF on plasma progesterone concentration, percentage of mares with endometritis, unwanted pregnancy and subsequent fertility in mares flushed without the use of PGF2α. Study design: Controlled experiments. Methods: Nine mares were inseminated in seven consecutive cycles (n = 63), to either perform an EF (n = 54) 7–9 days after ovulation or left pregnant (n = 9). PGF2α was not used to induce oestrus. Ultrasound examination and blood sampling were performed just before the EF and 72 h later to determine changes in progesterone concentration and signs of endometritis. Results: The overall percentage of positive EF/pregnancy was 55.5% (30/54) and 66.7% (6/9), respectively. The likelihood of pregnancy/positive EF in the first three cycles was 55.5% (15/29). This was not different (p > 0.1) from the fertility of the last four cycles (69.4%, 25/36). In five EF cycles (9.3%), mares had signs of endometritis and early luteolysis (progesterone <2 ng/mL) 72 h after EF. The reduction in progesterone concentration by 72 h after EF was greater (p < 0.05) for Day 9 (−2.3 ± 0.7 ng/mL) than Day 7 (−1.0 ± 0.8 ng/mL) or Day 8 (−1.3 ± 1.1 ng/mL) cycles. The progesterone concentration in non-flushed mares did not vary significantly during the sampled period (Day 7–12). There were 5 cycles in which the donor mare remained pregnant after the EF, although four were from a single mare. Main limitations: The mare population was limited to barren and maiden mares. The cycle order and operator allocation to each EF were not randomised. Conclusions: EF induces a subtle, but significant reduction in progesterone concentrations compared with non-EF cycles. However, the percentage of mares with EF-induced full luteolysis is low (9.3%). The fertility of mares after repeated EF without administration of PGF2α was unaffected; however, there is a considerable risk of unwanted pregnancy (5/27 = 18.5%) in donors from which an embryo was not recovered.