Effect of maternal starvation on fetal tissue nucleic acid, plasma amino acid and growth hormone concentration in sheep

The measurement of nucleic acids in fetal tissues as well as plasma growth hormone and amino acids was used in conjunction with fractional protein synthetic rates to investigate the mechanism of reduced fetal protein synthesis following acute maternal starvation. The nucleic acid analysis of fetal tissues from fed and 48 h starved ewes (120-130 days gestation) demonstrated a significant reduction in kidney RNA and heart DNA concentration in the starved fetuses. The RNA synthetic capacity (RNA/protein) was also seen to decrease in the starved fetuses both for liver and kidney tissue as was the protein/DNA in the lung tissue. Most revealing, however, were the measurements of RNA and DNA activity or the extent to which the protein synthesizing capacity was realized (g protein/g RNA or DNA/day). Significant reductions were observed in liver and brain RNA activity as well as the DNA activity of liver, lung, kidney and muscle. Plasma aminograms demonstrated reductions in maternal histidine, methionine and isoleucine as well as reductions in fetal glutamate and phenylalanine following starvation. Conversely, the fetal growth hormone levels were seen to rise under the influence of maternal starvation. The impact of maternal nutrient deprivation during gestation on fetal metabolism appears to depend on the ontogenic stage of development of specific tissues at the time the deprivation occurs.     

Protein synthesis in the gastrointestinal tissues of the ovine fetus

An isotope dilution procedure employing an 8h continuous infusion of L-[2,3,5,6-3H] tyrosine was used to determine fractional protein synthetic rates in the gastrointestinal tissues of ovine fetuses. The infusions were made into the inferior vena cava of the fetuses at 120-130 days of gestation. Immediately following the termination of the infusion the ewes were sacrificed and fetal tissues were collected, frozen in liquid nitrogen and stored at -20 C. The specific activity of the intracellular free and protein bound amino acid pools was determined from which the fractional synthetic rates (%/day) were calculated. These rates were as follows: reticulo-rumen, 49%; omasum, 10%; abomasum, 14%; proximal duodenum, 93%; and distal colon, 15%. The contribution of duodenum to the whole body protein synthesis was 10.5% while the contribution of the entire GIT (13.9%) was very close to that of liver (14.4%). The specific activity of tyrosine in the amniotic fluid and fetal ruminal fluid averaged 22% and 36% respectively of the specific activity in the plasma. The high turnover of tissue proteins in the fetal gastrointestinal tract as well as the presence of labelled tyrosine in the ruminal fluid indicate the functional importance of gastrointestinal activity in utero preparing the gastrointestinal tract for post-natal life.     

Effect of nutritional restriction in early pregnancy on isolated femoral artery function in mid-gestation fetal sheep

Unbalanced maternal nutrition affects fetal endocrine and cardiovascular systems, sometimes accompanied by changes in growth, although this is usually in late gestation. We determined the effect of moderate restriction for the first half of gestation of maternal dietary protein, or of total calorific intake on isolated resistance artery function of mid-gestation fetal sheep. Welsh Mountain ewes were nutritionally restricted by 30 % of the recommended nutrient intake (globally restricted) or 30 % of the recommended protein intake (protein-restricted), compared to control ewes fed 100 % of recommended nutrient intake, for ~12 days prior to conception and for the subsequent 70 days of gestation. At mid-gestation, fetal and placental weights were similar in all dietary groups. In isolated femoral arteries, the response curve to noradrenaline was reduced in protein-restricted group fetuses (   P < 0.05  ). Maximal relaxation (   P < 0.01  ) and sensitivity (   P < 0.05  ) to acetylcholine were markedly reduced in protein-restricted group fetuses, and to a smaller extent in globally restricted group fetuses (response curve,   P < 0.05  ). The dilator response (   P < 0.05  ) and sensitivity (   P < 0.05  ) to the α₂ agonist UK14304 was lower in protein-, but not in globally restricted group fetuses. The response (   P < 0.05  ) and sensitivity (   P < 0.05  ) to the nitric oxide donor sodium nitroprusside were reduced in protein-restricted group fetuses compared to controls. Our data show that dietary imbalance, in particular restricted protein, of the ewe can produce blunting of endothelial-dependent and -independent relaxation in systemic arteries from the mid-gestation fetus. These changes may precede perturbed late-gestation fetal and postnatal cardiovascular control.     

Protein synthesis and RNA in tissues of the pig.

The rate of protein synthesis in 75-kg pigs was measured by continuous intravenous infusion of [14C]tyrosine. In the whole body, over 600 g of protein were synthesized each day. In pigs, rats, and man the rate of protein synthesis in the whole body was related to metabolic rate. The fractional rate of synthesis of protein in the tissues was also measured. The proteins of visceral organs (liver kidney, lung, and spleen) were renewed at rates close to 20% per day, those of brain at 8% per day, heart 7% per day, and skeletal muscle 4% per day. A significant correlation was observed between the fractional rate of protein synthesis in the tissue and RNA concentration. Calculation of the total amount of protein synthesized in skeletal muscle of the pig (fractional rate of synthesis X protein content) shows that muscle contributes 42% of whole-body synthesis. By contrast, in the rat only 19% of whole-body synthesis occurs in muscle.     

Progesterone secretion and fetal development during prolonged starvation in the pig.

Roles of ovarian progesterone secretion and maternal nutrition in fetal development were investigated in a species that normally experiences considerable embryonic and fetal mortality. Pregnancies were maintained in 81% of Yorkshire pigs during prolonged starvation (e.g., 40 days; 0 kcal/day, water only) in either the middle third (days 30-70) or last third (days 70-110) of gestation compared with 100% in full-fed controls (7,028 kcal/day). In spite of severe maternal deprivation, fetal survival rates averaged 65% in starved dams and 63% in controls; mean number of living fetuses was 9.9 in starved and 9.6 in control dams. Fetal growth was reduced by maternal starvation during the middle third, but not the last third of pregnancy. Placental insufficiency was the primary cause of reduced fetal growth and resulted in abortion in a few of the dams. Progesterone in peripheral serum of dams starved either during middle or late pregnancy was maintained at levels similar (P greater than 0.05) to those in controls. Abortion occurred in starved dams only when serum progesterone concentrations dropped to less than 10 ng/ml within 3 days before loss of conceptuses.     

Interactions between maternal subtotal nephrectomy and salt: effects on renal function and the composition of plasma in the late gestation sheep fetus

Effects of altered maternal salt intake between 122 and 127 days gestation (term is 150 days) were studied in eight fetuses carried by ewes which had renal insufficiency caused by subtotal nephrectomy (STNxF) and seven fetuses carried by intact ewes (IntF). Plasma sodium and osmolality were increased in ewes with subtotal nephrectomy on a high-salt intake (0.17 m NaCl in place of drinking water for 5 days; P < 0.05). The STNxF had normal body weights. A high maternal salt intake did not affect fetal blood pressure or heart rate. Plasma osmolality was higher in STNxF (P < 0.001), and plasma sodium and osmolality were increased by high salt (P < 0.001 and P < 0.04, respectively). The STNxF had higher urinary osmolalities (P = 0.002), which were also increased by a high maternal salt intake (P = 0.03). Renal blood flow fell in STNxF in response to a high maternal salt intake, but increased in IntF (P = 0.003). In STNxF but not IntF, glomerular filtration rate and urinary protein excretion were positively related to fetal plasma renin levels (P < or = 0.01). It is concluded that the salt intake of pregnant ewes with renal insufficiency affects maternal and fetal osmolar balance, fetal plasma sodium and fetal renal function. Since STNxF also had altered renal haemodynamic responses to high maternal salt and evidence of renin-dependent glomerular filtration and protein excretion, we suggest that interactions between dietary salt and pre-existing maternal renal disease impair glomerular integrity and function in the fetus.     

The effects of pregnancy and maternal nutrition on the maternal renin-angiotensin system in sheep

Physiological changes occurring in the mother during pregnancy can determine the outcome of pregnancy in terms of birthweight and neonatal viability. Maternal adaptations include plasma volume expansion linked to enhanced activity of the renin-angiotensin system (RAS). The present study was designed to determine whether these changes occur very early in gestation, and the extent to which maternal nutrient restriction may compromise the maternal RAS. Using sheep, we have investigated the effects of pregnancy per se, maternal nutrient restriction and later restoration of maternal diet on maternal body weight, plasma volume and plasma renin concentration (PRC), and angiotensinogen (Aogen) and arginine vasopressin (AVP) concentration. During the period of placental growth (i.e. 28-80 days gestation) ewes were fed either a nutrient-restricted (NR) diet or were well fed (WF). NR ewes consumed between 3.2 and 3.8 MJ day(-1) of metabolisable energy (ME) which is close to 60 % of requirements taking into account the ME required for both ewe maintenance and growth of the conceptus in order to produce a 4.5 kg lamb at term. WF ewes consumed 150 % of ME requirements. Restoration of maternal diet between 80 and 140 days gestation (i.e. fed to satiety and consuming between 8 and 10.9 MJ day(-1), which is close to 150 % of ME requirements) followed previous nutrient restriction. Between pre-conception and 28 days gestation, plasma volume increased in conjunction with a decline in PRC and Aogen concentration. During the period of nutrient restriction ewe body weight did not increase and plasma volume was lower in NR than WF ewes. During this time there was no effect of maternal nutrition on PRC; however, Aogen concentration was lower in the NR group. From 80 days gestation following the rise in food intake for previously NR ewes, greater increases in ewe body weight, plasma volume and PRC occurred up to term compared with ewes that were well fed throughout gestation. Plasma AVP concentration was not significantly affected by either maternal nutrition or gestational age. In conclusion, the stimulus of moderately severe maternal nutrient restriction evoked smaller rises in maternal weight, plasma volume and Aogen concentration than occurred in ewes that were well fed throughout gestation. Following the restoration of maternal diet after 80 days gestation, PRC gradually rose to peak at term. These adaptations in the maternal RAS during the critical period of placental growth may have long-term effects on fetal development.     

Effects of starvation and diabetes on protein synthesis in lung.

Metabolism of lung proteins was investigated in rats starved 3 days or made diabetic with streptozotocin. Body weight was below normal in both groups, but lung weight decreased only in starved animals. Total lung protein and RNA (mg/lung) decreased during starvation and diabetes. Protein concentration (mg/g) was unchanged in either group of animals; RNA concentration decreased only during starvation. Protein synthesis, estimated in lungs perfused in situ, was reduced 22% in starvation, but remained unchanged in diabetes. Inhibition of protein synthesis was accounted for by loss of RNA. Ribosomal profiles were unchanged by starvation, suggesting an unaltered relationship between rates of peptide-chain initiation and elongation in vivo. Activity of an eIF-2-like initiation factor decreased during starvation in proportion to the loss of RNA. In diabetes, factor activity remained normal. Thus, starvation but not streptozotocin-induced diabetes, reduced the capacity of the lung to synthesize protein. No evidence for reduced efficiency of synthesis was observed.     

Effect of starvation on insulin receptors in rat brain

To determine the effect of starvation on brain insulin receptors, rats were fed 4 g of chow/day for 14 days and then P2 fraction membranes were prepared from different brain regions. Compared to the fed state, there was an 18% reduction of insulin binding in olfactory bulbs from starved animals, but no change in the cerebellum, frontal cortex, amygdala, medial hypothalamus or lateral hypothalamus. A 15% reduction of olfactory bulb insulin binding was obtained by totally starving animals for four days. When membrane content was measured using the plasma membrane marker Na/K ATPase, insulin binding decreased by 26% and 14% in olfactory bulb membranes from starved and totally starved animals, respectively. The starvation-induced change in olfactory bulb binding was due to a loss of binding sites and not a decrease in binding affinity. Non-specific catabolism of protein and a change in the composition of membranes following starvation were excluded as causes for this effect. As streptozotocin induced diabetes had no effect on brain insulin binding, it was concluded that hypoinsulinaemia associated with starvation had not caused the reduction in olfactory bulb binding. Under similar conditions of starvation and diabetes, insulin binding in liver plasma membranes increased 26% and 38%, respectively. At 8 and 14 days of starvation, the reductions in olfactory bulb insulin binding and body weight were similar. On refeeding for three days, there was no increase in insulin binding, although body weight increased 7%. On refeeding for eight days, olfactory bulb insulin and body weight had returned to near normal.(ABSTRACT TRUNCATED AT 250 WORDS)     

Body core temperature during food restriction in rats

Deep body temperature and locomotor activity of rats fed a reduced food amount (n = 9) and of starved rats (n = 9), were measured by implanted transmitters. Both groups were then refed ad libitum. The reduction in body temperature was significant for both groups, but larger in the starved rats than in the food restricted rats. There was a displacement of the circadian temperature rhythm in the starved rats. There were no significant differences in locomotor activity between groups until the start of refeeding. Rats fed reduced food amounts rapidly increased their activity, while the starved group retained a low activity for several days. Thermal conductance was reduced by 30% in both groups. This reduction in thermal conductance may explain how starving and semistarving rats are able to maintain core temperatures close to normal, even if resting metabolic rates are drastically reduced. The measured reduction in body core temperature signifies a change in the thermoregulatory 'set-point' during starvation.     

Maternal uniparental disomy of chromosome 16 and body stalk anomaly

We report on a fetus with placental trisomy 16, maternal uniparental disomy (UPD), and body stalk anomaly. Body stalk anomaly is a rare, fatal developmental abnormality consisting of a defective abdominal wall with abdominal organs in a sac outside the abdominal cavity covered by amnion adherent to the placenta with absence or severe shortness of the umbilical cord. Trisomy 16 was identified in the placenta in all cells. Amniocentesis was karyotypically normal. Parental origin studies showed maternal UPD for chromosome 16 in post-termination fetal tissue. The cause of the body stalk anomaly is not clearly defined. There are no other reports of placental karyotype or UPD investigations with body stalk anomaly. To our knowledge, this is the first report of placental trisomy 16, UPD in fetus, and body stalk anomaly, suggesting placental insufficiency or imprinting effects as cause of this anomaly. Am. J. Med. Genet. 94:284-286, 2000.     

Raised dietary n-6 polyunsaturated fatty acid intake increases 2-series prostaglandin production during labour in the ewe

Preterm labour is the major cause of perinatal morbidity and mortality in humans. The incidence is around 10% and the causes are often unknown. Consumption of dietary n -6 polyunsaturated fatty acids (PUFAs) in western societies is increasing. These are metabolized to arachidonic acid, the precursor for 2-series prostaglandins (PGs), major signalling molecules during labour. This study investigated the effect of dietary supplementation with linoleic acid (LA, 18: 2, n -6) on parturition. Ewes were fed a control or LA-supplemented diet from 100 days gestation. Labour was induced using a standardized glucocorticoid challenge (dexamethasone, Dex) to the fetus, starting on day 139. Electromyographic (EMG) activity and fetal and maternal circulating PG concentrations were monitored. One third of LA-fed ewes delivered early (pre-Dex) although basal uterine EMG activity preceding Dex was higher in control ewes  ( P < 0.05)  . A steep increase in EMG activity occurred 18–38 h after the start of Dex infusion. Twice basal EMG activity (defined as established labour) occurred on average 7 h earlier in the LA-supplemented ewes  ( P < 0.05)  . The basal concentrations of maternal and fetal PGFM and fetal PGE₂ were approximately doubled in LA-supplemented ewes before the start of Dex infusion  ( P < 0.01)  . The rise in fetal PGE₂ and maternal oestradiol concentrations post-Dex occurred earlier in the LA-supplemented ewes. All PG measurements remained significantly higher in the LA-supplemented ewes during labour onset. This study suggests that consumption of a high LA diet in late pregnancy can enhance placental PG production and may thus increase the risk of preterm labour.     

Effect of maternal nutrient restriction in early gestation on responses of the hypothalamic-pituitary-adrenal axis to acute isocapnic hypoxaemia in late gestation fetal sheep

Epidemiological and experimental evidence suggests that maternal undernutrition during pregnancy may alter development of fetal organ systems. We have demonstrated previously that fetal hypothalamic-pituitary-adrenal (HPA) axis responses to exogenous corticotropin-releasing hormone (CRH) + arginine vasopressin (AVP), or adrenocorticotrophin hormone (ACTH), are reduced in fetuses of mildly undernourished ewes. To examine these effects further we tested HPA axis responses to acute isocapnic hypoxaemia in fetal sheep at 114-129 days gestation (dGA), following 15% reduction in maternal nutritional intake between 0 and 70 dGA. Fetuses from control (C) and nutrient-restricted (R) ewes were chronically catheterised and plasma ACTH and cortisol responses were determined at 114-115, 120-123 and 126-129 dGA during hypoxaemia (1 h) induced by lowering the maternal inspired O2 fraction (FI,O2). Basal plasma cortisol concentrations and HPA axis responses at 114-115 and 120-123 dGA did not differ between C and R fetuses. At 126-129 dGA, both plasma ACTH (P < 0.01) and cortisol (P < 0.05) responses were smaller in R fetuses compared to C fetuses. Fetal blood gas status, fetal body weight, body proportions and organ weights did not differ between the groups. We conclude that mild maternal undernutrition alters development of the fetal HPA axis producing a reduction in pituitary and adrenal responsiveness to endogenous stimuli.     

Development of fetal and placental innate immune responses during establishment of persistent infection with bovine viral diarrhea virus

Transplacental viral infections are dependent upon complex interactions between feto-placental and maternal immune responses and the stage of fetal development at which the infection occurs. Bovine viral diarrhea virus (BVDV) has the ability to cross the placenta and infect the fetus. Infection early in gestation with non-cytopathic (ncp) BVDV leads to persistent infection. Establishment of fetal persistent infection results in life-long viremia, virus-specific immunotolerance, and may have detrimental developmental consequences. We have previously shown that heifers infected experimentally with ncp BVDV type 2 on d. 75 of gestation had transient robust up-regulation of the type I interferon (IFN) stimulated genes (ISGs) 3-15 days after viral inoculation. Blood from persistently infected (PI) fetuses, collected 115 days post maternal infection, demonstrated moderate chronic up-regulation of ISGs. This infection model was used to delineate timing of the development of innate immune responses in the fetus and placenta during establishment of persistent infection. It was hypothesized that: (i) chronic stimulation of innate immune responses occurs following infection of the fetus and (ii) placental production of the type I IFN contributes to up-regulation of ISGs in PI fetuses. PI fetuses, generated by intranasal inoculation of pregnant heifers with ncp BVDV, and control fetuses from uninfected heifers, were collected via Cesarean sections on d. 82, 89, 97, 192, and 245 of gestation. Fetal viremia was confirmed starting on d. 89. Significant up-regulation of mRNA encoding cytosolic dsRNA sensors -RIG-I and MDA5 - was detected on d. 82-192. Detection of viral dsRNA by cytosolic sensors leads to the stimulation of ISGs, which was reflected in significant up-regulation of ISG15 mRNA in fetal blood on d. 89, 97, and 192. No difference in IFN-α and IFN-β mRNA concentration was found in fetal blood or caruncular tissue, while a significant increase in both IFN-α and IFN-β mRNA was seen in cotyledons from PI fetuses on d. 192. It is concluded that fetuses respond to early gestational ncp BVDV infection by induction of the type I IFN pathway, resulting in chronic up-regulation of ISGs. Cotyledonary tissue contributes to up-regulation of ISGs by increased production of IFNs. The innate immune response might partially curtail viral replication in PI fetuses, but is not able to eliminate the virus in the absence of a virus-specific adaptive immune response.     

Pathogenesis of bovine neosporosis

The protozoan parasite Neospora caninum is a major pathogen of cattle and dogs, being a significant cause of abortion in cattle in many countries. It is one of the most efficiently transmitted parasites, with up to 90% of cattle infected in some herds. The pathogenesis of abortion due to Neospora is complex and only partially understood. Losses occur after a primary infection during pregnancy but more commonly as the result of recrudescence of a persistent infection during pregnancy. Parasitaemia is followed by invasion of the placenta and fetus. It is suggested that abortion occurs when primary parasite-induced placental damage jeopardises fetal survival directly or causes release of maternal prostaglandins that in turn cause luteolysis and abortion. Fetal damage may also occur due to primary tissue damage caused by the multiplication of N. caninum in the fetus or due to insufficient oxygen/nutrition, secondary to placental damage. In addition, maternal immune expulsion of the fetus may occur associated with maternal placental inflammation and the release of maternal pro-inflammatory cytokines in the placenta. Thus N. caninum is a primary pathogen capable of causing abortion either through maternal placental inflammation, maternal and fetal placental necrosis, fetal damage, or a combination of all three. The question of how N. caninum kills the fetus exposes the complex and finely balanced biological processes that have evolved to permit bovine and other mammalian pregnancies to occur. Defining these immunological mechanisms will shed light on potential methods of control of bovine neosporosis and enrich our understanding of the continuity of mammalian and protozoal survival.     

Mechanism of acute fetal cardiovascular depression after maternal inflammatory challenge in mouse

Intra-amniotic lipopolysaccharide (LPS) causes an acute inflammatory response and cardiac dysfunction in fetal mice. We hypothesized that the placenta protects the fetus against maternally administered bacterial toxins, delaying the onset of a fetal inflammatory response and vascular compromise. At 14 to 15 days of gestation, DBA mice were randomized to receive LPS (2.4 mg/kg) or vehicle intraperitoneally. Doppler ultrasonography of fetal cardiovascular hemodynamics was performed before and 6 hours after maternal LPS. Six hours after the LPS, maternal serum concentrations of tumor necrosis factor-alpha and interleukin (IL)-6 (P < 0.05) were increased. Placenta showed severe maternal vascular dilatation and congestion. The expressions of tumor necrosis factor-alpha, IL-1alpha, and IL-6 (P < 0.05) were increased, and the expression of Toll-like receptor 4 was constitutive in placenta. The expression of Toll-like receptor 2 increased (P < 0.05) and was detected in labyrinthine macrophages. No inflammatory activation was found in fetal tissues, and amniotic fluid revealed no significant increase in cytokines. The ultrasonographic examination demonstrated increased fetal cardiac afterload after LPS, with 65% of the fetuses exhibiting atrioventricular valve regurgitation. In conclusion, maternal inflammatory insult activates placental labyrinthine macrophages leading to an acute increase in placental vascular resistance and fetal cardiac dysfunction without an inflammatory response in fetus.     

Distribution of ionic sulfate, lithium, and bromide across the sheep placenta.

Salts of sulfate, lithium, and bromine were injected or infused intravenously into ewes in the last trimester of gestation. Ewes and fetuses had indwelling catheters; most fetuses were nephrectomized. Concentrations were measured in paired maternal and fetal samples over periods of 4--14 days. Maternal excretion of sulfate was too rapid to permit near equilibration of fetal and maternal plasma concentrations; the results, however, did not support the existence of a large potential difference across the exchange barrier. The concentrations of Li+ (given by continuous infusion) and 82Br- in maternal plasma did not change rapidly. The concentrations of these tracers in fetal plasma rose until they were nearly equal to the maternal plasma concentrations. Steady-state transplacental potentials, calculated by use of the Nernst equation, were 5.2 +/- 2.0 (SEM) mV (n = 26) for Li+ and -2.2 +/- 0.8 (SEM) mV (n = 10) for Br-. Nernst potentials calculated from previously measured maternal and fetal plasma concentrations of Na+, K+, Mg2+, and Cl- were +0.4, +3.6, +0.5, and -1.4 mV. We concluded that, of the total potential difference of about -50 mV (fetus negative) between the fetal lamb and the ewe, only a few mV are dropped across the placental exchange barrier.     

Kinetics of lactate and glucose metabolism in the pregnant ewe and conceptus

Two monotocous and two ditocous ewes were infused at 124-130 days of gestation with a mixture of L-[U-14C]lactate and D-[6-3H]glucose via a maternal or umbilical catheter, separate days being used for each infusion. Plateaux-specific radioactivities of plasma lactate and glucose were used to derive a four-pool model describing the fluxes between the lactate and glucose pools of the infused conceptus and mother. The average turnover rate of lactate was 23.3 and 13.2 mg carbon min-1 in the conceptus and 32.0 and 44.0 mg carbon min-1 in the mother for monotocous and ditocous ewes, respectively. Glycolysis rates within both conceptus and mother in all sheep were high, accounting for about 80 and 60% of the respective rates of lactate turnover. The synthesis of glucose from lactate accounted for 13 and 31% of the glucose turnover in the mother in monotocous and ditocous ewes, respectively, but was insignificant in the conceptus. Glycolysis within the conceptus used only glucose which had entered and mixed with the conceptus glucose pool; there was no direct transfer of carbon from the maternal glucose pool to the conceptus lactate pool. This finding is an important validation for the use of tracer methods to determine glucose use within the whole conceptus rather than within fetal corporeal tissues alone.     

MyD88 Signaling Is Directly Involved in the Development of Murine Placental Malaria

Malaria is a widespread infectious disease caused by the parasite Plasmodium. During pregnancy, malaria infection leads to a range of complications that can affect both the mother and fetus, including stillbirth, infant mortality, and low birth weight. In this study, we utilized a mouse model of placental malaria (PM) infection to determine the importance of the protein MyD88 in the host immune response to Plasmodium during pregnancy. Initially, we demonstrated that Plasmodium berghei NK65GFP adhered to placental tissue via chondroitin sulfate A and induced PM in mice with a C57BL/6 genetic background. To evaluate the involvement of MyD88 in the pathology of PM, we performed a histopathological analysis of placentas obtained from MyD88^−/− and wild-type (WT) mice following infection on the 19th gestational day. Our data demonstrated that the detrimental placental alterations observed in the infected mice were correlated with the expression of MyD88. Moreover, in the absence of this protein, production of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) was significantly reduced in the infected mice. More importantly, in contrast to fetuses from infected WT mice, which exhibited a reduction in body weight, the fetuses from infected MyD88^−/− mice did not display significant weight loss compared to their noninfected littermates. In addition, we observed a decrement of maternal care associated with malaria infection, which was attenuated in the MyD88-deficient mice. Collectively, the results of this study illustrate the pivotal importance of the MyD88 signaling pathway in the pathogenesis of placental malaria, thus presenting new possibilities for targeting MyD88 in therapeutic interventions.