Grossesse | EPFL Graph Search

La grossesse, appelée aussi gestation humaine, est l'état d'une femme enceinte, c'est-à-dire portant un embryon ou un fœtus humain, en principe au sein de l'utérus, qui est dit gravide. En général, elle fait suite à un rapport sexuel, débute selon le point de vue à partir de la fécondation (fusion d'un ovule et d'un spermatozoïde) ou de la nidation (implantation de l'embryon dans l'utérus), et se déroule jusqu'à l'expulsion de l'organisme engendré. La durée moyenne de la fécondation à l'accouchement pour une grossesse unique est de et deux jours, soit un peu moins de neuf mois, une durée largement reprise dans la culture. Dans les faits, cette durée est variable selon les femmes et le déroulement de la grossesse. Ainsi, une grossesse normale dure entre d'aménorrhée (SA) ; on parlera alors de grossesse menée à terme. Pour une durée inférieure à 37 SA, on parle de prématurité et, pour une durée supérieure à 41 SA, on parle de postmaturité. En obstétrique, il existe trois types de gr

Hormonal regulation of Stat5 in the mammary gland - from signaling to morphogenesis

Sergio Klinke

The mammary gland development is regulated by steroid and peptide hormones and occurs mainly after birth, compared to the majority of the other organs in the body. The principal hormones responsible for the breast development are the estrogen, the progesterone, the growth hormone, the epidermal growth factor and the prolactin. The latter one is of specific interest since it is required for further development of the gland through pregnancy and lactation. During pregnancy and lactation, alveolar structures develop and differentiate into secretory cells. The signal transducer and activator of transcription 5 (Stat5) is known to be the main effector of prolactin signaling during pregnancy, inducing alveologenesis and differentiation of epithelial cells into secretory cells. I investigated if Stat5 has a role before pregnancy. Protein expression as well as mRNA expression analysis of glands from ovariectomized mice which were artificially stimulated with ovarian hormones (estrogen and progesterone) and control vehicle showed evidences that Stat5 expression can be stimulated by these two hormones. Contrary to the role established until now for stat5 in the mammary gland, I found by fluorescence visualization of Stat5-null epithelium as well as whole mount staining of the same glands that Stat5 is required even before pregnancy since null epithelium showed highly reduced growth already in 3 weeks-old virgin mice. This may indicate a new role for this protein in cell proliferation or survival in early stages of mouse mammary development. Furthermore, transplantation experiment of Stat5-null epithelium into wild-type recipient mice showed that pregnancy state was not able to rescue the normal phenotype. This may be due to complete loss of these cells which happened during the 5 weeks left for the transplanted epithelium to expand the cleared fat pad. This discovery opens a new debate on Stat5 role in the mammary gland development.

2008

Waddlia chondrophila induces systemic infection, organ pathology, and elicits Th1-associated humoral immunity in a murine model of genital infection

David Baud, Joël Gyger, Alessandra Piersigilli

Waddlia chondrophila is a known bovine abortigenic Ch/amydia-related bacterium that has been associated with adverse pregnancy outcomes in human. However, there is a lack of knowledge regarding how W chondrophila infection spreads, its ability to elicit an immune response and induce pathology. A murine model of genital infection was developed to investigate the pathogenicity and immune response associated with a W chondrophila infection. Genital inoculation of the bacterial agent resulted in a dose-dependent infection that spread to lumbar lymph nodes and successively to spleen and liver. Bacterial induced pathology peaked on day 14, characterized by leukocyte infiltration (uterine horn, liver, and spleen), necrosis (liver) and extramedullary hematopoiesis (spleen). Immunohistochemistry demonstrated the presence of a large number of W chondrophila in the spleen on day 14. Robust IgG titers were detected by day 14 and remained high until day 52. IgG isotypes consisted of high IgG2a, moderate IgG3 and no detectable IgG1, indicating a Th1-associated immune response. This study provides the first evidence that W chondrophila genital infection is capable of inducing a systemic infection that spreads to major organs, induces uterus, spleen, and liver pathology and elicits a Th1-skewed humoral response. This new animal model will help our understanding of the mechanisms related to intracellular bacteria-induced miscarriages, the most frequent complication of pregnancy that affects one in four women.

Frontiers Media Sa2015

Role of canonical Wnt signaling in mammary gland development

Renuga Devi Rajaram

The female reproductive hormones estrogens, progesterone, and prolactin control postnatal breast development and are important to breast carcinogenesis. In particular, exposure to progesterone is tightly linked to breast cancer risk. Using the mouse as a model system to study the mechanisms through which hormones elicit morphogenetic changes in the mammary gland in vivo, we demonstrated that progesterone acts by a paracrine mechanism and identified Wnt4 as a target of progesterone important in mediating side branch formation. The mechanisms underlying Wnt4 function remains poorly understood. To understand the pattern of canonical Wnt signaling activation during mammary gland development and to address which cellular compartment of the mammary gland is activated by canonical Wnt signaling, a reporter mouse model was utilized in which the lacZ gene is under the control of endogenous Axin2 promoter, classical target promoter of canonical Wnt signaling. Analysis of reporter mice at different developmental stages of mammary gland development showed the highest reporter activity during early pregnancy which correlated with the time of side branch formation. At this stage, β-galactosidase activity was found exclusively in myoepithelial cells. Overexpression of Wnt1 from MMTV promoter increases reporter activity in the myoepithelium. Gene expression analysis on FACS sorted luminal and myoepithelial cells shows that known canonical Wnt signaling pathway components such as receptors and co receptors as well as targets are specifically expressed in the myoepithelial compartment further supporting the notion that myoepithelial cells are the target cells for Wnt1 and Wnt4 secreted by luminal cells. Consistent with a model whereby progesterone induced Wnt4 secretion results in canonical Wnt signaling activation, reporter activity was induced by progesterone treatment and lacZ expression increased during diestrus when serum progesterone levels are high under physiological conditions. Analysis of contralateral mammary glands engrafted with PR-/-.Axin2 lacZ and PR+/-.Axin2 lacZ epithelium during pregnancy revealed that intact PR signaling is required to activate canonical Wnt signaling. Similar experiments with Wnt4-/-.Axin2 lacZ and Wnt4+/+.Axin2 lacZ mammary epithelium showed that reporter activation relies on Wnt4. Histological analysis on mammary glands in which β-catenin was ablated using MMTV-Cre revealed that β-catenin deleted cells were present only in the luminal epithelial compartment and showed that β-catenin deleted myoepithelial cells cannot participate in side branch formation. Similarly, ectopic expression of dominant negative β-catenin in wt MECs reduced side branching indicating that canonical Wnt signaling mediated by β-catenin is required for side branching. Furthermore, constitutive activation of β-catenin in the mammary epithelium was sufficient to induce side branch formation in virgin mice. In Wnt4 mutant epithelium, proliferation of progesterone receptor positive and negative cells were significantly reduced in response to progesterone treatment. Wnt signaling has been implicated in stem/progenitor activation in several tissues including mammary gland. Consistent with Wnt4 activating stem/progenitors, serial transplantation assays revealed that Wnt4-/- epithelium failed to reconstitute already at 2nd to 3rd generation when the wt has the ability to reconstitute up to seven generations indicating that Wnt4 is required for stem cell function while Wnt4 is dispensable for embryonic and rudimentary mammary gland formation. Histology and gene expression analysis in late pregnancy showed that Wnt4 mutant epithelia were able to differentiate and produce milk proteins, further supporting the thought that Wnt4 function is important for stem/progenitor cell activity and not required for differentiation. Taken together, I report that Wnt4 induces canonical Wnt signaling in myoepithelial cells and activation of canonical Wnt signaling is required and sufficient for side branching. Moreover, Wnt4 function is essential for mammary stem/progenitor cells.

EPFL2010