Characterization of Proliferative Activity in Bovine Placentomes Between Day 150 and Parturition by Quantitative Immunohistochemical Detection of Ki67-Antigen

Schuler, Gerhard; Wirth, C; Klisch, K; Failing, Klaus; Hoffmann, Bernd

doi:10.1046/j.1439-0531.2000.d01-12.x

Cited by 15 publications

(9 citation statements)

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“…The detection of ERa in the caruncles suggests that estrogens produced in the trophoblast are involved in the regulation of growth and differentiation of the maternal part of the placentome in a paracrine manner (Hoffmann and Schuler, 2002;Schuler et al, 2002). This hypothesis was further substantiated by our data on proliferative activity in ERa-positive caruncular stromal cells (Schuler et al, 2000), which clearly parallels local estrone tissue concentrations (Tsumagari et al, 1993).…”

Section: Introductionsupporting

confidence: 78%

Estrogen Receptor β (ERβ) Is Expressed Differently From ERα in Bovine Placentomes

Schuler

Teichmann²,

Taubert³

et al. 2005

Exp Clin Endocrinol Diabetes

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The functions of placental estrogens in cattle are still poorly understood. In order to investigate a putative role as local regulators of placental growth, differentiation and functions via estrogen receptor beta (ERbeta), the expression of this ER isoform was determined in bovine placentomes obtained from cows at midgestation (days 110-150; n=7), late gestation (days 180-280; n=9), from prepartal cows (sampling immediately after the prepartal decline in maternal progesterone blood levels became obvious; n=3) and from cows at normal term (n=5) on the protein and mRNA level. By means of immunohistochemistry using a monoclonal antibody against human ERbeta (clone PPG5/10), nuclear signals were found in numerous cell types of the fetal (cotyledon) and maternal (caruncle) component of the placentomes with highest intensities in mature trophoblast giant cells (TGC), fetal and maternal vascular cells and caruncular stromal cells, in which the percentage of positive cells increased from 58.9+/-2.3 and 59.1+/-3.3 at mid- and late gestation to 65.1+/-4.9 and 69.4+/-4.2 in prepartal and parturient cows, resp. (p<0.0001). Clear staining of uninucleated trophoblast cells was only observed in prepartal and parturient animals. Conventional RT-PCR confirmed ERbeta expression in caruncles and cotyledons at all phases under investigation. With semi-quantitative real-time RT-PCR higher levels of ERbeta-specific mRNA were measured in cotyledons compared to caruncles (p<0.01). The results show that in contrast to ERalpha, which is only expressed in the caruncle, ERbeta is also extensively expressed in the cotyledon and suggest a role of ERbeta primarily in TGC differentiation and placental angiogenesis and/or vascular functions.

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Section: Introductionsupporting

confidence: 78%

Estrogen Receptor β (ERβ) Is Expressed Differently From ERα in Bovine Placentomes

Schuler

Teichmann²,

Taubert³

et al. 2005

Exp Clin Endocrinol Diabetes

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“…Yet, in the microcotyledonary T of the equine placenta, no morphologically or functionally different T cell types have been identified so far, and in contrast to humans and ruminants, no continuous differentiation of highly differentiated T cells from less-differentiated precursors has been described. Obviously, in equine microcotyledons, proliferation of T cells is more strictly related to growth (Gerstenberg et al 1999) than to cell turnover, as it has been shown in bovine placentomes (Wooding and Wathes 1980;Schuler et al 2000). Yet, as peripheral maternal oestrogen concentrations and the percentage of ERa-positive cells in microplacentomes grossly reflect placental growth rates, placental oestrogens may be involved in the autocrine and paracrine stimulation of formation and growth of microplacentomes, especially via ERa.…”

Section: Discussionmentioning

confidence: 88%

Immunohistochemical Localization of Oestrogen Receptors α and β, Progesterone Receptor and Aromatase in the Equine Placenta

Abd-Elnaeim¹,

Derar

Wilsher

et al. 2009

Reprod Domestic Animals

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The functions of placental oestrogens during equine pregnancy are still unclear. Yet, they may act predominantly as local regulators of growth and differentiation in the microplacentomes. Thus, expression patterns of oestrogen receptors (ERs) alpha and beta were investigated in the microcotyledonary placenta from pregnant mares at 110, 121, 179, 199 and 309 days of gestation by immunohistochemistry. In microplacentomes, both the ER isoforms were detected in trophoblast (T) cells, chorionic villous stroma (FS), microcaruncular epithelium (ME) and microcaruncular stroma (MS). Proportions of positive cells were 38-91% (T), 11-41% (FS), 55-89% (ME), 17-51% (MS) for ERalpha and 66-76% (T), 21-37% (FS), 41-68% (ME) and 24-55% (MS) for ERbeta. Between days 110 and 199, proportions of cells positive for progesterone receptor (PR) varied between 19% and 62% (T), 3% and 50% (CS), 15% and 46% (ME), and 4% and 33% (MS). At day 309, PR was virtually absent in T, CS and ME (percentages < 0.1), whereas in MS 14.3% of cells were still positive. The expression of ERs and PR in equine microplacentomes gives evidence for a role of placental steroids as regulators of placental growth, differentiation and function. The detection of ERalpha, ERbeta and PR in foetal and maternal vascular tissue suggests that placental steroids are also involved in the control of placental angiogenesis and /or vascular functions. The co-localization of ERs with aromatase in T suggests auto- or intracrine functions of oestrogens in this cell type.

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“…With the detection of a high estrogen receptor (ER ) expression in caruncular stromal and epithelial cells , a new light was shed on the role of placental estrogens in cattle, suggesting a role primarily as local regulators of caruncular growth, differentiation and functions. Corresponding to a distinct and widespread expression of ER in the caruncular epithelium, a surprisingly high proliferation and turnover was detected throughout gestation in this cell type leading to the concept of the bovine caruncles as specialized endometrial holocrine glands " colonized " by chorionic villi ( Schuler et al, 2000 ;Hoffmann and Schuler, 2002 ). Thus estrogens synthesized in the trophoblast may stimulate proliferation in the adjacent caruncular epithelium to produce a histiotrophe-like cell detritus which could serve as a signifi cant source of nutrients for the fetus in addition to nutrients passing over into the fetal compartment by diffusion or membrane associated transport mechanisms.…”

Section: Evidence For a Role Of Placental Steroids As Local Regulatormentioning

confidence: 99%

Placental Steroids in Cattle: Hormones, Placental Growth Factors or By-products of Trophoblast Giant Cell Differentiation?

Schuler¹,

Greven²,

Kowalewski³

et al. 2008

Exp Clin Endocrinol Diabetes

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The bovine placenta produces large amounts of steroids, mainly estrone (E1) and progesterone (P4). Specific features of bovine placental steroidogenesis are 1) the expression of all enzymes needed for the production of estrogens from cholesterol in the trophoblast 2) an only marginal and temporal contribution to peripheral maternal P4 levels restricted to a period between approx. days 150 - 240 of gestation 3) the predominance of sulfoconjugated over free E1 and 4) a complementary setting of steroidogenic enzymes in the two morphologically discriminable trophoblast cell types, the uninucleated trophoblast cells (UTC) and the trophoblast giant cells (TGC). In cattle so far no definite information is available on the specific biological roles of placental estrogens and P4. However, the detection of estrogen receptors and progesterone receptors in the placentomes suggests a role primarily as local regulators of caruncular growth, differentiation and functions. Inconsistent with a function as a caruncular growth factor is the strong evidence that in cattle placental estrogens enter the maternal compartment almost completely as estrone sulfate (E1S), which is not active at classical nuclear receptors. On the other hand, E1S may be converted locally to free active estrogens via the action of steroid sulfatase (StS), which has been detected in specific parts of the bovine caruncular epithelium. Alternatively or in addition, StS expression in the caruncular epithelium may serve the utilization of sulfated neutral steroid precursors (e.g. pregnenolone sulfate or cholesterol sulfate) supplied with maternal blood, thus providing free substrates for further metabolization in the adjacent trophoblast. The down-regulation of P450scc and P450c17 and the up-regulation of 3beta-HSD and aromatase during the differentiation of TGC from UTC in parallel with the up-regulation of ER beta and estrogen sulfotransferase in maturing TGC suggests a function of placental estrogens primarily as autoor intracrine regulators during this process and assigns to conjugated placental estrogens a role as inactivated by-products of TGC differentiation intended for excretion. Collectively, despite some evidence from recent studies for putative roles of placental steroids in cattle their exact functions in the bovine species remain still undefined.

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Characterization of Proliferative Activity in Bovine Placentomes Between Day 150 and Parturition by Quantitative Immunohistochemical Detection of Ki67-Antigen

Cited by 15 publications

References 0 publications

Estrogen Receptor β (ERβ) Is Expressed Differently From ERα in Bovine Placentomes

Estrogen Receptor β (ERβ) Is Expressed Differently From ERα in Bovine Placentomes

Immunohistochemical Localization of Oestrogen Receptors α and β, Progesterone Receptor and Aromatase in the Equine Placenta

Placental Steroids in Cattle: Hormones, Placental Growth Factors or By-products of Trophoblast Giant Cell Differentiation?

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