Characteristics of ceruloplasmin synthesis in embryogenesis and in the early postnatal period of laboratory white rats

The dynamics of ceruloplasmin content was studied by immunochemical methods in the postimplantation rat embryos and postnatal animals. Ten to twenty two day old embryos contained ceruloplasmin (CP) in yolk sac, serum, and amniotic fluid. The highest CP levels were found in yolk sac. CP concentration profiles were almost identical in the serum and amniotic fluid being the highest on the 12th day (0.26 mg%) and the lowest (0.04) on the 16th day of gestation. CP concentration in the serum increased rapidly up to 3.5 mg% from the 17th day of gestation till the term (22nd day) while remaining at a constant and rather low level in the amniotic fluid. Within 16-18 days after birth, CP concentration in the serum remained at the level of 11 +/- 0.3 mg%. Later on it gradually increased and attained plateau (46-48 mg%) by the time of sex maturity. The maternal serum CP does not penetrate, in the embryo, as can be inferred from the experiments with 125I-CP injected into pregnant rats. Differences in the CP degradation rate and modes were found between the embryos and postnatal rats. It is suggested that CP is initially synthesized by the yolk sac endoderm during organogenesis (10-16 days of gestation) and predominantly by the liver during the foetal period (17-22 days).     

Pregnancy in Hystricomorpha: Gestational age and embryonic-fetal development of agouti (Dasyprocta prymnolopha, Wagler 1831) estimated by ultrasonography

Thirty-one pregnant agoutis, between Days 9 and 103 of gestation (Day 1 = day of detection of sperm in the vaginal smear), underwent B-mode ultrasonography; gestational sac diameter (GSD), crown-rump length (CRL), embryonic-fetal diameter (EFD), and placenta diameter (PD) were measured. There were positive correlations (P < 0.05) between GSD and CRL (r = 0.98), GSD and PD (r = 0.88), CRL and PD (r = 0.86), days of gestation (DG) and CRL (r = 0.85), and DG and PD (r = 0.73). The gestational sac was first observed on Day 14. The embryo was first seen on Day 18 in 9/31 of pregnant agoutis and on Day 22 in 20/31 of pregnant agoutis. Heartbeats were detected from the Day 25 and placentas were observed in 100% of the animals from Day 25. Early limb bud and ossification of the fetal skull were identified on Days 27 (15/31) and 45 (24/31), respectively. Fetal orientation (head and body) was evident from Day 40, the stomach, liver and lungs were identified on Day 50, the kidneys were reliably seen only on Day 55, and the aorta and vena cava were seen on Day 70. The fetal bowel and the urinary bladder were the last structures to be observed (Day 85). Ultrasonography was effective for early pregnancy diagnosis in agouti and for obtaining information on embryonic and fetal structures that could be used to predict gestational age and birth, thereby contributing to their reproductive management in captivity.     

An in vitro morphological study of the mouse visceral yolk sac and possible yolk sac immunocyte precursors

Summary Mouse visceral yolk sac has been organ cultured from 9 days of gestation, a time prior to the thymus being lymphoid, until 12 days of gestation, a time after which the thymus is lymphoid. During the culture period the endodermal epithelial cells survived well, erythropoiesis diminished, endothelial-lined cavities formed in the mesodermal mass, and cells developed which have been classified as large, medium and small immunocyte precursors. The cytoplasm of the immunocyte precursors contains polysomes, spherical mitochondria, a few profiles of rough endoplasmic reticulum, occasional granules and a large Golgi complex. This study offers morphological support for the yolk sac origin of immunocyte precursors in the mouse which may seed the thymus and liver.Supported by NIH Grant AI 13486-01     

Embryonic macrophages of early rat yolk sac: Immunohistochemistry and ultrastructure with reference to endodermal cell layer

Macrophages are multifunctional cells that participate in numerous biological processes; they actively phagocytose foreign particles and cell debris. Embryonic tissue macrophages are present at early stages of mammalian development; their ontogeny and function is still under investigation. Our study used immunohistochemistry and electron microscopy to investigate early rat yolk sac macrophages using mouse antirat macrophage monoclonal antibodies (mAb) Mar 1 and Mar 3 produced by our laboratory. Mar 3 mAb revealed the first emergence of immature macrophages in the rat yolk sac at fetal day nine coinciding with the beginning of yolk sac haemopoiesis that consisted mainly of erythropoiesis, while Mar 1 mAb detected specifically rat yolk sac macrophages at about the 13th to 14th day of gestation. Immunoreactivity against Mar mAbs was mainly located in the yolk sac endodermal cell layer, which may signify endodermal origin of the yolk sac macrophages. Ultrastructurally mature yolk sac macrophages contained numerous endocytic vesicles or vacuoles, well-developed Golgi saccules and many electron dense granules in their cytoplasm and a number of microvillous projections from the cell surface. After establishment of the circulation between yolk sac and embryo, Mar 3 positive cells were also demonstrated inside fetal undifferentiated mesenchymal tissue at fetal day 12. The study demonstrated the first emergence of immature yolk sac macrophages being among the earliest haemopoietic cells formed in mammalian development. Thus, Mar mAbs managed to detect macrophage differentiation antigens through their development early in the rat yolk sac.     

Cadmium-induced forelimb ectrodactyly: a proposed mechanism of teratogenesis

We have attempted to elucidate the mechanism of cadmium teratogenesis utilizing inbred mouse strains sensitive (C57BL/6J) or resistant (SWV) to the embryotoxic effect of this common heavy metal contaminant. Carbonic anhydrase activity of whole-embryo homogenates was moderately depressed in C57BL/6J mice compared to a slight and transient decrease in the resistant SWV mice. Embryonic erythrocytes were similarly examined, and the cadmium did not have any effect on carbonic anhydrase activity in either strain. Likewise, histochemical examination of carbonic anhydrase activity did not reveal any effect of cadmium in the embryos of their strain. Generally, the zinc concentration of embryos was not affected by cadmium administration. However, increased levels of zinc were observed in cadmium-exposed yolk sacs of both strains suggesting that cadmium produces an adverse effect on yolk sac function. Untreated C57BL/6J units (embryo plus surrounding extraembryonic membranes), embryos, and yolk sacs had much lower hemoglobin concentrations than those observed in untreated SWV units, embryos, and yolk sacs. Additionally, cadmium exposure significantly decreased C57BL/6J embryonic hemoglobin levels on gestation day 10 (PM) and increased C57BL/6J yolk sac hemoglobin levels on gestation days 10 (AM) and 10 (PM). No difference in hemoglobin concentration was observed between untreated and cadmium-treated SWV embryos or yolk sacs. We propose that cadmium induces forelimb ectrodactyly by creating an acidotic embryonic environment and that the primary site at which cadmium exerts its teratogenic effect might be the yolk sac.     

Studies on mouse autoreactive cells: III. Fetal development of autorosette-forming cells

Self-recognition assessed by rosette formation by lymphocytes with erythrocytes of syngeneic or autologous origin is a very primitive function that is present before lymphoid system development proper in the thymus. Autologous rosette-forming cells (A-RFC) have been found in the very early yolk sac of pregnant mice of 10–11 days gestation. Moreover, when these 10- to 11-days' gestation pregnant mice were subcutaneously injected with facteur thymique sérique (FTS) 1 day before A-RFC examination, it appears that FTS reduces the number of A-RFC in the yolk sac by 63%. Thus it has not been possible to determine whether FTS acted by changing the migration capacity or the expression of receptors on the cell surface.     

Embryo‐fetal erythroid megaloblasts in the human coelomic cavity

The coelomic cavity is part of the extraembryonic mesoderm, surrounding amniotic cavity, embryo, and yolk sac in the early gestation. It is now believed to represent an important transfer interface and a reservoir of nutrients for the embryo. Coelocentesis by ultrasound‐guided transvaginal puncture offers an easier access to the early human embryo, from 28 days post‐fertilization. However, despite some studies about its biochemical composition being reported, our knowledge about the presence of cellular elements and their quality in this compartment are still limited. Here we studied human coelomic fluids sampled from 6.6 (48 days) to 10 weeks of gestation, demonstrating the presence of functional embryonic erythroid precursors, that is, megaloblasts in the coelomic cavity. The ease of access of the coelomic cavity could allow the development of novel strategies for diagnostic or therapeutic purposes by ultrasound imaging and ultrasound‐guided puncture. J. Cell. Physiol. 225: 385–389, 2010. © 2010 Wiley‐Liss, Inc.     

Viviparity in the halfbeak genera Dermogenys and Nomorhamphus (Teleostei: Hemiramphidae)

Gravid ovaries were examined histologically from two species of Nomorhamphus and 21 populations of Dermogenys. In addition, changes in dry-weight throughout gestation are provided for 15 populations. The ovaries are paired organs running along the lateral body wall and are separated along most of their length. In all specimens examined, embryos are fertilized within the ovarian follicle. Viviparity in these species is divided herein into five categories designated types I–V. In types I and II the entire gestation period is intrafollicular, whereas in types III–V only the early stages of gestation are intrafollicular with the major period of development occurring in the ovarian lumen (intraluminal). Type I is characterized by the retention of a large amount of yolk throughout gestation. Superfetation is not observed. Populations of D. pusilla from Vietnam and Thailand decrease in dry-weight throughout gestation. This, coupled with the slight vascularization of the yolk sac, suggests strict lecithotrophy. Populations of D. pusilla from Singapore and Bangladesh undergo an increase in dry weight and exhibit an increased vascularization of the yolk sac, suggesting a form of unspecialized matrotrophy. Type II is characterized by a small amount of yolk, an expansion of the coelomic cavity and pericardial sac, and a simple cuboidal epithelium on the general body surfaces. Superfetation occurs with up to three broods present within a single ovary. Dermogenys pusilla from Sabah, D. orientalis and Dermogenys sp. (Sulawesi) exhibit the type II form of viviparity. Dermogenys vivipara from the eastern Philippine islands of Culion and Busuanga exhibit characteristics considered intermediate between type I and II. These results are compared with those from other viviparous species exhibiting intrafollicular gestation. In species with types III–V (intraluminal gestation), developing oocytes are restricted to a distinct ridge of ovigerous tissue extending along the entire length of the ovary. Two species, D. viviparus (Luzon, Philippines) and Dermogenys sp. (Luzon) have the type III form of viviparity. In this form, oocytes are small (0.8–1.0 mm) with little yolk reserves and embryos, covered with a simple cuboidal epithelium and possessing an expanded belly sac, are retained within the follicles until a late fin-bud stage. Type III embryos found within the ovarian lumen have a greatly expanded belly sac and remain covered by a simple cuboidal epithelium until parturition. Superfetation is present in these species with two broods observed simultaneously within a single ovary. Five species, D. megarrhamphus, D. weberi, D. viviparus (Jolo, Philippines), Nomorhamphus sp. (Sulawesi), and N. towoetii, were observed with the type IV form of viviparity. Embryos in this category are evacuated into the ovarian lumen prior to a fin-bud stage and retain a large yolk mass throughout development. Superfetation is absent in these species. A differentform of viviparity (type V) is present in D. ebrardtii in which embryos appear to obtain nutrients through a form of oophagy and aldelphophagy (feeding on developing oocytes or less-developed siblings). In all specimens with intraluminal development, atretic oocytes within the ovigerous ridge are abundant. These findings support the hypothesis that current species and generic limits may be artificial and underscores the potential of histological evidence for phylogenetic analysis of this group. J. Morphol. 234:295–317, 1997. © 1997 Wiley-Liss, Inc.     

Origin and developmental patterns of lactase and other glycosidases in sheep amniotic and allantoic fluid.

Intestinal lactase activity (with its associated cellobiase, 4-methylumbelliferyl-beta-galactosidase and -beta-glucosidase activities) was used as a specific intestinal marker enzyme to study the release of protein and enzymes of intestinal origin in sheep amniotic fluid during gestation. In amniotic fluid, intestinal lactase activity peaked at 66--85 days of gestation and then decreased with gestation. This enzyme activity was very low or absent in allantoic fluid throughout gestation suggesting that there is no important transfer of amniotic fluid lactase towards the allantoic cavity. Maltase and 4-methylumbelliferyl-alpha-glucosidase showed no statistically significant variation with gestation in both amniotic and allantoic fluid whereas alpha-galactosidase and N-acetyl-beta-hexosaminidase which were first higher in allantoic than in amniotic fluid increased in amniotic fluid to reach allantoic fluid levels near term. Such patterns are consistent with the suggestion that the fetal urine is a source of alpha-galactosidase and N-acety-beta-hexosaminidase activities and that sheep urine is first accumulated in the allantoic sac via the urachus up to 86--90 days of gestation and thereafter passes more and more into the amniotic sac.     

Embryonic development and nourishment in the viviparous fish Poecilia vivipara (Cyprinodontiformes: Poeciliidae)

While viviparity confers protection to the embryos during gestation, it increases energetic costs for the mother, which acquires new relations to its offspring. Maternal–fetal transfer of nutrients can occur in different patterns: as lecithotrophy (nourished by yolk) or matrotrophy (nourished by the mother). The development of Poecilia vivipara embryos was described macroscopically and microscopically, and the form of nutritional provisioning was identified. Embryonic development was divided into three prefertilization and seven postfertilization stages. The first organ to appear is the notochord, followed by the nervous, digestive and cardiovascular systems, and then by muscles and eyes. Embryonic nutritional provisioning was lecithotrophic, with yolk persisting until the last developmental stages and rich in proteins and polysaccharides. This kind of embryonic nutrition confirms the pattern found in the family Poeciliidae.     

Erythropoietin. Receptor characteristics during the ontogeny of hamster yolk sac erythroid cells

Erythropoietin (Epo) binds specifically to receptors on the surface membrane of responsive erythroid cells. In search of ontogenic changes in Epo receptor behavior, we studied characteristics of specific binding to hamster yolk sac erythroid cells during hamster ontogeny. We detected receptors specific for Epo on these cells throughout the duration of their intravascular existence (hamster gestational days 8 through 13). These receptors are saturable at an Epo concentration of 1.2 nM in the incubation medium. Attainment of equilibrium of binding prior to hormone internalization, a requirement for receptor binding assays, was possible at 10 degrees C but not at 37 degrees C. Hence, all incubations of cells with Epo were carried out at 10 degrees C. Data on specific binding analyzed by the method of Scatchard demonstrated that yolk sac erythroid cells possess a single class of Epo receptors at each stage of gestation examined. Binding affinity and numbers of receptors per cell change as ontogeny progresses: Kd (the dissociation constant) increases, a phenomenon observed in other differentiating cell systems, whereas the number of receptors per cell peaks on gestational day 10. The variability in number of receptors per cell is consonant with up and down regulation controlled by Epo availability. We propose that the progressive increase in Kd might be best explained by ontogenic changes in cell membrane structure contiguous to the receptors themselves.     

Early pregnancy assessment with transvaginal ultrasound scanning.

OBJECTIVE: To establish normal parameters in early pregnancy through transvaginal ultrasonography so that gestational age can be determined and to correlate the sonographic findings with serum human chorionic gonadotropin (hCG) levels calibrated against the first international reference preparation standard. SETTING: Infertility clinic. PATIENTS: Thirty-five women with normal intrauterine pregnancy. INTERVENTIONS: Serial measurement of the serum hCG level and the diameter of the gestational sac through transvaginal ultrasonography. MAIN RESULTS: The gestational sac could not be visualized when the hCG level was less than 1100 IU/L. The average growth rate of the sac was 0.9 mm/d. The threshold values for sac diameter, serum hCG level and gestational age below which the yolk sac was not visible were 3.7 mm, 1900 IU/L and 36 days respectively; the corresponding values above which the yolk sac was always visible were 6.7 mm, 5800 IU/L and 40 days. The threshold values below which cardiac activity was not visible were 8.3 mm, 9200 IU/L and 41 days respectively, and the corresponding values above which cardiac activity was always visible were 14.0 mm, 24,000 IU/L and 46 days. The mean gestational ages and the 95% confidence and prediction intervals were tabulated so that measurement of the gestational sac diameter could be used to estimate gestational age early in normal pregnancy. CONCLUSIONS: Transvaginal ultrasonography enables detection of an intrauterine sac and reliable estimation of gestational age on the basis of sac dimensions before an embryo can be seen.     

Reproduction,placentation, and embryonic development of the Atlantic sharpnose shark,Rhizoprionodon terraenovae

The Atlantic sharpnose shark Rhizoprionodon terraenovae (Richardson) is a small carcharhinid that is a common year-round resident along the southeast coast of the United States. It is viviparous and its embryos develop an epithelio-vitelline placenta. Females enter shallow water to give birth in late May and early June. Mating occurs shortly after parturition, and four to seven eggs are ovulated. Fertilized eggs attain the blastoderm stage in early June to early July. Separate compartments for each egg are formed in the uterus when the embryos reach 3–30 mm. Embryos depend on yolk for the first 8 weeks of development. When embryos reach 72 mm their yolk supply is nearly depleted and they shift to matrotrophic nutrition. When the embryos reach 40–55 mm, placental development begins with the vascularization of the yolk sac where it contacts the uterine wall. Implantation occurs at an age of 8–10 weeks by which time the embryos reach 70–85 mm. The expanding yolk sac engulfs the maternal placental villi, and its surface interdigitates with the villi to form the placenta. The rest of the lumenal surface of the uterus is covered by non-placental villi that appear shortly after implantation. Histotrophe production by the non-placental villi begins just after their formation. The placenta grows continuously during gestation. The egg envelope is present throughout gestation, separating maternal and fetal tissues. Embryos develop numerous appendiculae on the umbilical cord. Young sharks are born at 290–320 mm after a gestation period of 11 to 12 months. © 1993 Wiley-Liss, Inc.     

Distribution of 3H in rat conceptus cultured in vitro following brief administration of [3H]thymidine

Rat embryos with intact visceral yolk sacs, explanted at 12 1/2 days of gestation, were cultured in vitro for up to 60 min in medium consisting of fetal calf serum, Eagle's MEM, and [3H]thymidine (1.2 kBq ml-1), using the roller bottle method. The total amount of 3H incorporated into the conceptus during the 60-min incubation was 79.2 Bq, and approximately 33, 23, and 44% of this activity was distributed to the embryo, the yolk sac, and the fluid in the exocoelom and amniotic cavity, respectively. The rate of 3H accumulation in conceptuses decreased with time in culture. It appeared that the decrease in the viability of the conceptus was not responsible for this phenomenon. The concentration of 3H in the yolk sac, i.e., 3H activity per gram wet weight, was 2.1 times that in the medium at the end of culture. In contrast, the 3H concentration in the embryo was significantly lower than that in the medium. These findings suggest that the visceral yolk sac of rat conceptuses may act as a barrier to the transport of tritiated thymidine between the medium and embryo.     

The detection and monitoring of early pregnancy in the vervet monkey (Cercopithecus aethiops) with the use of ultrasound and correlation with reproductive steroid hormones

Twenty early pregnancies were diagnosed and monitored in vervet monkeys by ultrasonography. Non-gravid uteri became increasingly echogenic from cycle days 7 to 26. The first definite sign of pregnancy was a gestational cavity of 2 mm (+/- 0.80) at 33.0 (+/- 1.48) days menstrual age, which was also used to date all subsequent features. Earlier signs, such as an endometrial line swelling or endometrial 'pregnancy' ring, as reported for other non-human primate species, could not be reliably and consistently used to diagnose pregnancy in vervet monkeys. A rapid increase of the gestational cavity size from days 37 to 49 corresponded closely to a rapid increase in plasma progesterone concentration from day 39 to 49. The first yolk sac was recognizable at 38.0 days (+/- 3.10) and measured 3.3 mm (+/- 0.40) in diameter. A heart beat could be detected at 45.5 (+/- 1.73) days and the size of the first measurable embryo at 35 days was 2 mm. The dating of most features was within the range reported for other non-human primate species.     

The pattern of apolipoprotein B100 containing lipoprotein subclasses produced by the isolated visceral rat yolk sac depends on developmental stage and fatty acid availability

Explants of visceral rat yolk sacs from gestational days 16, 18 and 22 were used for studying developmental changes of secretion and density distribution of lipoproteins, particularly of those containing apoB. Moreover, the influence of fatty acid supply on the amount and density distribution of secreted apolipoproteins was studied on day 18 of gestation. Active lipoprotein production was observed in yolk sacs taken on days 16 and 18 of gestation. It declined considerably on day 22 of gestation in parallel with the production of total protein, triacylglycerols and cholesterol. On all gestational days, apoB floated mainly in the LDL range (⩾ 70%) with differences in the distribution pattern of LDL subclasses. The lowest density of secreted LDL was found on day 18 of gestation (peak at d = 1.025 g/ml) followed by day 16 (peak at d = 1.035 g/ml) and day 22 of gestation (peak at d = 1.045 g/ml). ApoIV, apoE and apoAI floated exclusively in the HDL range with a peak at d = 1.089 g/ml independently of the gestational day. After incubation of yolk sacs from the 18th day of gestation with 0.4 mM or 0.8 mM oleate, the density of secreted apoB containing particles was decreased (peaks in the VLDL and IDL density range), whereas palmitate in the same concentrations caused a redistribution of secreted apoB toward higher densities (peaks at d ≥ g/ml). Taken together, the data provide evidence that the density of L.DL subclasses produced by isolated yalk sacs between days 16 and 22 of gestation depended on the gestational stage. Moreover, addition of unsaturated or saturated fatty acids to the organ culture differently affected the secretory rate and the density of lipoproteins delivered by yolk sacs on day 18 of gestation.     

Embryo implantation and proteinase activities in a marsupial (Macropus eugenii)

Summary Embryo implantation remains superficial (epithelio-chorial type) in most marsupials including the Macropodidae, but does involve formation of specialized contact zones of the trophoblast with the uterine epithelium. Since in eutherian mammals proteinases appear to play a central role in implantation-initiation mechanisms, a systematic histochemical investigation of proteinase patterns as related to implantation was performed in the tammar wallaby, Macropus eugenii (Macropodidae).Tammar uteri with embryos were collected at diapause and at days 7, 17, 18, 19, 20, 21 and 26 of the 27-day gestational period. Proteinase patterns were studied using a sensitive histochemical gelatin-substrate-film test previously optimized for the detection of trophoblast-dependent proteinase (blastolemmase) in the rabbit. Proteinase patterns were correlated with light-microscopical morphology of the processes of shedding of the extracellular embryo coverings (shell membrane) and attachment of the trophoblast to the uterine epithelium.At acid pH values an intracellular proteinase is detected in yolk sac endoderm and trophoblast as well as in endometrial glands and certain stromal cells. This enzyme is proposed to be a cathepsin indicating high catabolic activity connected particularly with protein transport from the endometrium into the yolk sac. Peak activity is found in the avascular (bilaminar) yolk sac at the phase when contact with the endometrium is being established.A particularly interesting proteinase active at alkaline pH values is detected in the trophoblast-endoderm complex. This enzyme appears to be extruded into the interface between trophoblast and uterine epithelium where it shows maximal activity for only approximately one day, around day (18-)19, exclusively in the bilaminar (avascular) yolk sac. The activity is correlated with the process of shedding of the extracellular embryo coverings (shell membrane) and of subsequent attachment of the trophoblast to the uterine epithelium, in the bilaminar but not the trilaminar (vascular) yolk-sac region. This is the first report on an extracellular (alkaline) proteinase activity possibly serving a specific function in embryo implantation in a marsupial.Abreviations BYS bilaminar (avascular) yolk sac membrane = bilaminar omphalopleure - dp.c. days post coitum - d RPY days after removal of pouch young - TYS trilaminar (vascular) yolk sac membrane = trilaminar omphalopleure Preliminary reports on portions of these investigations were presented at the 14th Annual Meeting of the Society for the Study of Reproduction 1981 (Biol Reprod 24 Suppl 1, p 78 A, 1981) and at the 3. Arbeitstagung der Anatomischen Gesellschaft 1982 (Anat Anz 153, 268, 1983)     

Effect of amphotericin B and gestational age on sodium transport across the rat visceral yolk sac placenta in vitro

The transport properties of the rat visceral yolk sac placenta from Days 14.5 to 18.5 of gestation were studied in vitro. All tissues had a positive potential difference, fetal side relative to maternal side, and showed net Na transport towards the fetus. Basal short-circuit current and net Na flux increased rapidly with gestational age over the period studied. Amphotericin B applied to the maternal surface of the yolk sac stimulated current and net Na flux, indicating that the apical membrane Na permeability limited transport and revealing a reserve capacity for transport. Contrary to their basal values, current and Na flux following treatment with amphotericin were independent of gestational age.     

Maternal high density lipoproteins affect fetal mass and extra-embryonic fetal tissue sterol metabolism in the mouse

Previous studies have shown that antibodies to cubulin, a receptor on the yolk sac that binds high density lipoproteins (HDL) and cobalamin, induce fetal abnormalities. Mice with markedly low concentrations of plasma HDL-cholesterol (HDL-C) give birth to healthy pups, however. To establish whether maternal HDL-C has a role in fetal development, sterol metabolism was studied in the fetus and extra-embryonic fetal tissues in wild-type and apolipoprotein A-I-deficient mice (apoAI-/-). Maternal HDL-C content was markedly greater in apoAI+/+ mice prior to pregnancy and at 13 days into gestation. By 17 days into gestation, HDL-C content was similar between both types of mice. Fetuses from apoAI (-/- x -/-) matings were 16;-25% smaller than control mice at 13 and 17 days of gestation and contained less cholesterol. The differences in size and cholesterol content were not due to a lack of cholesterol synthesis or apoA-I in the fetus. In the yolk sac and placenta, sterol synthesis rates were approximately 50% greater in the 13-day-old apoAI-/- mice as compared to the apoAI+/+ mice. Even though synthesis rates were greater, cholesterol concentrations were 22% lower in the yolk sac and similar in the placenta of apoAI-/- mice as compared to tissues of wild-type mice. These data suggest that a difference in maternal HDL-C concentration or composition can affect the size of the fetus and sterol metabolism of the yolk sac and placenta in the mouse.