Fetal development of in vitro-produced embryos: Possible association with uterine function

Abstract Gestational nutrient restriction causes epigenetic and phenotypic changes that affect multiple physiological processes in the offspring. Gonadotropes, the cells in the anterior pituitary that secrete luteinizing hormone (LH) and follicle-stimulating hormone (FSH), are particularly sensitive to nutritional changes during fetal development. Our objective herein was to investigate the effects of gestational nutrient restriction on LH protein content and number of gonadotropes in the fetal bovine pituitary. We hypothesized that moderate nutrient restriction during mid to late gestation decreases pituitary LH production, which is associated with a reduced number of gonadotropes. Embryos were produced in vitro with X-bearing semen from a single sire then split to generate monozygotic twins. Each identical twin was transferred to a virgin dam yielding four sets of female twins. At gestational d 158, the dams were randomly assigned into two groups, one fed 100% NRC requirements (control) and the other fed 70% of NRC requirements (restricted) during the last trimester of gestation, ensuring each pair of twins had one twin in each group. At gestational d 265, the fetuses (n = 4/group) were euthanized by barbiturate overdose, and the pituitaries were collected. Western blots were performed using an ovine LH-specific antibody (Dr. A.F. Parlow, NIDDK). The total LH protein content in the pituitary tended to be decreased in the restricted fetuses compared to controls (P < 0.10). However, immunohistochemistry analysis of the pituitary did not reveal any significant changes in the total number of LH-positive cells (control = 460±23 cells/0.5 mm2; restricted = 496±45 cells/0.5 mm2, P = 0.58). In conclusion, while maternal nutrient restriction during gestation resulted in a trend of reduced LH content in the fetal pituitary, immunohistological findings suggest that these changes are likely related to the individual potential of each gonadotrope to produce LH, rather than alterations in cell differentiation during fetal development.

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Building a stem cell-based primate uterus

Communications Biology ◽

10.1038/s42003-021-02233-8 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Sophie Bergmann ◽

Magdalena Schindler ◽

Clara Munger ◽

Christopher A. Penfold ◽

Thorsten E. Boroviak

Keyword(s):

Stem Cell ◽

Fetal Development ◽

Embryo Implantation ◽

In Vitro Models ◽

Uterine Tissue ◽

Controlled Assembly ◽

Uterine Cancers ◽

Term Births ◽

Key Questions

AbstractThe uterus is the organ for embryo implantation and fetal development. Most current models of the uterus are centred around capturing its function during later stages of pregnancy to increase the survival in pre-term births. However, in vitro models focusing on the uterine tissue itself would allow modelling of pathologies including endometriosis and uterine cancers, and open new avenues to investigate embryo implantation and human development. Motivated by these key questions, we discuss how stem cell-based uteri may be engineered from constituent cell parts, either as advanced self-organising cultures, or by controlled assembly through microfluidic and print-based technologies.

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X Irradiation in G 2 Phase of Two-Cell Mouse Embryos in Vitro: Cleavage, Blastulation, Cell Kinetics, and Fetal Development

Radiation Research ◽

10.2307/3575831 ◽

1982 ◽

Vol 91 (2) ◽

pp. 219 ◽

Cited By ~ 20

Author(s):

M. Molls ◽

C. Streffer ◽

D. van Beuningen ◽

N. Zamboglou

Keyword(s):

Fetal Development ◽

Cell Kinetics ◽

Mouse Embryos ◽

X Irradiation

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Inclusion of bovine lipoproteins and the vitamin E analogue, Trolox, during in vitro culture of bovine embryos changes both embryo and fetal development

Reproduction Fertility and Development ◽

10.1071/rd11034 ◽

2012 ◽

Vol 24 (2) ◽

pp. 309 ◽

Cited By ~ 5

Author(s):

J. A. Rooke ◽

R. G. Watt ◽

C. J. Ashworth ◽

T. G. McEvoy

Keyword(s):

Vitamin E ◽

In Vitro Culture ◽

Fetal Development ◽

Fatty Acid Content ◽

Liver Weight ◽

Fetal Weight ◽

Interactive Effects ◽

Bovine Embryo ◽

Zygote Development

This experiment investigated effects of lipoproteins and Trolox (vitamin E analogue) on bovine embryo and fetal development. The treatments were: in vitro culture (IVC) in synthetic oviducal fluid alone (SOF); with bovine lipoproteins (2% v/v; SOFLP); with Trolox (100 μM; SOFT); and with lipoproteins and Trolox (SOFLPT). In vitro culture with lipoproteins increased fatty acid content of blastocysts (P < 0.001) whereas inclusion of Trolox had no effect (P > 0.05). Whereas lipoproteins reduced zygote development to blastocysts (P = 0.03), Trolox facilitated increased development (P < 0.001) and counteracted the reduction observed with lipoproteins (interaction, P = 0.009). Lipoproteins also compromised (P < 0.001) but presence of Trolox (P > 0.05) had no effect on blastocyst morphological grade. Pregnancy rates resulting from synchronous transfer of IVP embryos were not affected by IVC treatment. At Day 70 of pregnancy, compared with SOF, fetal weight was lower in SOFLP but not SOFLPT (interaction, P < 0.001). Liver weight (g kg–1 fetal weight) was greater (P = 0.03) in treatments containing Trolox. Placentome numbers were greater in SOF and SOFLPT compared with SOFLP and SOFT (interaction, P = 0.002); superior embryo grades were also associated with increased numbers of placentomes (P = 0.024). In conclusion, the interactive effects of lipoprotein and Trolox inclusion on in vitro embryo development were also evident in fetal development at Day 70.

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Injury effects of ginkgolide B on maturation of mouse oocytes, fertilization, and fetal development in vitro and in vivo

Toxicology Letters ◽

10.1016/j.toxlet.2009.03.004 ◽

2009 ◽

Vol 188 (1) ◽

pp. 63-69 ◽

Cited By ~ 16

Author(s):

Nion-Heng Shiao ◽

Wen-Hsiung Chan

Keyword(s):

Fetal Development ◽

Ginkgolide B ◽

Mouse Oocytes ◽

Development In Vitro

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Poorly controlled diabetes mellitus alters placental structure, efficiency, and plasticity

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001243 ◽

2020 ◽

Vol 8 (1) ◽

pp. e001243

Author(s):

Jackson Nteeba ◽

Kaela M Varberg ◽

Regan L Scott ◽

Mikaela E Simon ◽

Khursheed Iqbal ◽

...

Keyword(s):

Diabetes Mellitus ◽

Fetal Development ◽

Trophoblast Invasion ◽

Ambient Conditions ◽

Placental Development ◽

Junctional Zone ◽

Pregnant Rat ◽

Elevated Glucose ◽

The Impact

IntroductionThe hemochorial placenta provides a critical barrier at the maternal–fetal interface to modulate maternal immune tolerance and enable gas and nutrient exchange between mother and conceptus. Pregnancy outcomes are adversely affected by diabetes mellitus; however, the effects of poorly controlled diabetes on placental formation, and subsequently fetal development, are not fully understood.Research design and methodsStreptozotocin was used to induce hyperglycemia in pregnant rats for the purpose of investigating the impact of poorly controlled diabetes on placental formation and fetal development. The experimental paradigm of hypoxia exposure in the pregnant rat was also used to assess properties of placental plasticity. Euglycemic and hyperglycemic rats were exposed to ambient conditions (~21% oxygen) or hypoxia (10.5% oxygen) beginning on gestation day (gd) 6.5 and sacrificed on gd 13.5. To determine whether the interaction of hyperglycemia and hypoxia was directly altering trophoblast lineage development, rat trophoblast stem (TS) cells were cultured in high glucose (25 mM) and/or exposed to low oxygen (0.5% to 1.5%).ResultsDiabetes caused placentomegaly and placental malformation, decreasing placental efficiency and fetal size. Elevated glucose disrupted rat TS cell differentiation in vitro. Evidence of altered trophoblast differentiation was also observed in vivo, as hyperglycemia affected the junctional zone transcriptome and interfered with intrauterine trophoblast invasion and uterine spiral artery remodeling. When exposed to hypoxia, hyperglycemic rats showed decreased proliferation and ectoplacental cone development on gd 9.5 and complete pregnancy loss by gd 13.5. Furthermore, elevated glucose concentrations inhibited TS cell responses to hypoxia in vitro.ConclusionsOverall, these results indicate that alterations in placental development, efficiency, and plasticity could contribute to the suboptimal fetal outcomes in offspring from pregnancies complicated by poorly controlled diabetes.

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Epithelial-mesenchymal interactions in the developing kidney lead to expression of tenascin in the mesenchyme.

The Journal of Cell Biology ◽

10.1083/jcb.105.1.599 ◽

1987 ◽

Vol 105 (1) ◽

pp. 599-608 ◽

Cited By ~ 161

Author(s):

E Aufderheide ◽

R Chiquet-Ehrismann ◽

P Ekblom

Keyword(s):

Embryonic Development ◽

Fetal Development ◽

Culture System ◽

De Novo ◽

Mouse Kidney ◽

Adult Mice ◽

In Vitro Culture System ◽

Tightly Coupled ◽

Developing Kidney

Tenascin, a mesenchymal extracellular matrix glycoprotein, has been implicated in epithelial-mesenchymal interactions during fetal development (Chiquet-Ehrismann, R., E. J. Mackie, C. A. Pearson, T. Sakakura, 1986, Cell, 47:131-139). We have now investigated the expression of tenascin during embryonic development of the mouse kidney. In this system, mesenchymal cells convert into epithelial cells as a result of a tissue interaction. By immunofluorescence, tenascin could not be found in the mesenchyme until kidney tubule epithelial began to form. It then became detectable around condensates and s-shaped bodies, the early stages of tubulogenesis. In an in vitro culture system, tenascin expression by the mesenchyme is tightly coupled to the de novo formation of epithelial, and does not occur if tubulogenesis is suppressed. The results strongly suggest that the formation of the new epithelium stimulates the expression of tenascin in the nearby mesenchyme. During postnatal development, the expression of tenascin decreases and the spatial distribution changes. In kidneys from adult mice, no tenascin can be found in the cortex, but interspersed patches of staining are visible in the medullary stroma. The results strongly support the view that tenascin is involved in epithelial-mesenchymal interactions. It could therefore be crucial for embryonic development.

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Disruption of insulin-like growth factor-II imprinting during embryonic development rescues the dwarf phenotype of mice null for pregnancy-associated plasma protein-A

Journal of Endocrinology ◽

10.1677/joe.1.06259 ◽

2005 ◽

Vol 186 (2) ◽

pp. 325-331 ◽

Cited By ~ 43

Author(s):

Laurie K Bale ◽

Cheryl A Conover

Keyword(s):

Body Size ◽

Growth Factor ◽

Plasma Protein ◽

Fetal Development ◽

Protein A ◽

Receptor Activation ◽

Mutant Mice ◽

Insulin Like Growth Factor ◽

Dwarf Phenotype

Pregnancy-associated plasma protein-A (PAPP-A), an insulin-like growth factor-binding protein (IGFBP) protease, increases insulin-like growth factor (IGF) activity through cleavage of inhibitory IGFBP-4 and the consequent release of IGF peptide for receptor activation. Mice homozygous for targeted disruption of the PAPP-A gene are born as proportional dwarfs and exhibit retarded bone ossification during fetal development. Phenotype and in vitro data support a model in which decreased IGF-II bioavailability during embryogenesis results in growth retardation and reduction in overall body size. To test the hypothesis that an increase in IGF-II during embryogenesis would overcome the growth deficiencies, PAPP-A-null mice were crossed with ΔH19 mutant mice, which have increased IGF-II expression and fetal overgrowth due to disruption of IgfII imprinting. ΔH19 mutant mice were 126% and PAPP-A-null mice were 74% the size of controls at birth. These size differences were evident at embryonic day 16.5. Importantly, double mutants were indistinguishable from controls both in terms of size and skeletal development. Body size programmed during embryo development persisted post-natally. Thus, disruption of IgfII imprinting and consequent elevation in IGF-II during fetal development was associated with rescue of the dwarf phenotype and ossification defects of PAPP-A-null mice. These data provide strong genetic evidence that PAPP-A plays an essential role in determining IGF-II bioavailability for optimal fetal growth and development.

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