Abstract:Two peaks of aromatase activities were detected in bovine cotyledons, 2.76 +/- 0.96 pmol min-1 mg-1 protein at month five of gestation and 3.62 +/- 0.78 pmol min-1 mg-1 protein immediately after parturition, but aromatase activity in caruncles was very low throughout gestation. Oestrone concentrations in the cotyledons and caruncles were 0.93 +/- 0.50 and 1.51 +/- 0.69 ng mg-1 protein at month five of gestation, but 4.31 +/- 1.66 and 3.36 +/- 0.98 ng mg-1 protein immediately after parturition, indicating a bip… Show more
“…Staining in placentomes from animals at day 90 and 180 clearly showed higher signal intensity in the trophoblast covering primary villi compared with other parts of the villous tree. Observations in placentomes from a cow after induction of parturition and in a cow at normal term indicates that prepartal up-regulation of aromatase activity (Tsumagari et al 1993) follows a pattern similar to the one identified for P450c17. The up-regulation of P450arom and oestrogen receptor b (Schuler et al 2005) concomitant with TGC differentiation points to an autocrine regulatory role of placental oestrogens during this process in addition to their previously postulated functions as local caruncular growth factor (Schuler et al 2002).…”
Section: Day 90mentioning
confidence: 57%
“…In vitro investigations using placental homogenates suggest that, as in the sheep (Mason et al 1989), P450c17 activity in bovine trophoblast is significantly up-regulated at parturition (Schuler et al 1994). Aromatisation in microsomes prepared from bovine cotyledons exhibits a distinct peak in the fifth month of gestation but is low thereafter until the last month of gestation, when it increases again around the time of parturition (Tsumagari et al 1993). Only sporadic, and in part contradictory, information is available on the expression of P450arom on a cellular level in bovine placentomes.…”
No definitive information is yet available on the steroidogenic capacity of the two morphologically distinct cell types forming the bovine trophoblast, the uninucleated trophoblast cells (UTCs) and the trophoblast giant cells (TGCs). Hence, in order to localise 17a-hydroxylase-C17,20-lyase (P450c17) on a cellular level and to monitor its expression as a function of gestational age, placentomes from pregnant (days 80 -284; n 5 19), prepartal (days 273 -282; 24 -36 h prior to the onset of labour; n 5 3) and parturient cows (n 5 5) were immunostained for P450c17 using an antiserum against the recombinant bovine enzyme. At all stages investigated, P450c17 was exclusively found in the UTCs of chorionic villi (CV), where staining was ubiquitous between days 80 and 160, but was largely restricted to primary CV and the branching sites of secondary CV between days 160 and 240. Thereafter, a distinct ubiquitous staining reoccurred in the UTCs of all CV in late pregnant, prepartal and parturient animals. Using an antiserum against human aromatase cytochrome P450 (P450arom), specific cytoplasmic staining was observed in TGCs. In placentomes from pregnant cows, staining intensity was higher in mature compared with immature TGCs and was more pronounced in the trophoblast covering big stem villi compared with the trophoblast at other sites of the villous tree. In placentomes of a parturient cow, specific staining was only found in mature TGCs that survived the normal, but substantial, prepartal decline in TGC numbers. These results clearly showed that bovine UTCs and TGCs exhibit different steroidogenic capacities, constituting a 'two-cell' organisation for oestrogen synthesis. P450c17 expression appears to be quickly down-regulated and P450arom is up-regulated when UTCs enter the TGC differentiation pathway.
“…Staining in placentomes from animals at day 90 and 180 clearly showed higher signal intensity in the trophoblast covering primary villi compared with other parts of the villous tree. Observations in placentomes from a cow after induction of parturition and in a cow at normal term indicates that prepartal up-regulation of aromatase activity (Tsumagari et al 1993) follows a pattern similar to the one identified for P450c17. The up-regulation of P450arom and oestrogen receptor b (Schuler et al 2005) concomitant with TGC differentiation points to an autocrine regulatory role of placental oestrogens during this process in addition to their previously postulated functions as local caruncular growth factor (Schuler et al 2002).…”
Section: Day 90mentioning
confidence: 57%
“…In vitro investigations using placental homogenates suggest that, as in the sheep (Mason et al 1989), P450c17 activity in bovine trophoblast is significantly up-regulated at parturition (Schuler et al 1994). Aromatisation in microsomes prepared from bovine cotyledons exhibits a distinct peak in the fifth month of gestation but is low thereafter until the last month of gestation, when it increases again around the time of parturition (Tsumagari et al 1993). Only sporadic, and in part contradictory, information is available on the expression of P450arom on a cellular level in bovine placentomes.…”
No definitive information is yet available on the steroidogenic capacity of the two morphologically distinct cell types forming the bovine trophoblast, the uninucleated trophoblast cells (UTCs) and the trophoblast giant cells (TGCs). Hence, in order to localise 17a-hydroxylase-C17,20-lyase (P450c17) on a cellular level and to monitor its expression as a function of gestational age, placentomes from pregnant (days 80 -284; n 5 19), prepartal (days 273 -282; 24 -36 h prior to the onset of labour; n 5 3) and parturient cows (n 5 5) were immunostained for P450c17 using an antiserum against the recombinant bovine enzyme. At all stages investigated, P450c17 was exclusively found in the UTCs of chorionic villi (CV), where staining was ubiquitous between days 80 and 160, but was largely restricted to primary CV and the branching sites of secondary CV between days 160 and 240. Thereafter, a distinct ubiquitous staining reoccurred in the UTCs of all CV in late pregnant, prepartal and parturient animals. Using an antiserum against human aromatase cytochrome P450 (P450arom), specific cytoplasmic staining was observed in TGCs. In placentomes from pregnant cows, staining intensity was higher in mature compared with immature TGCs and was more pronounced in the trophoblast covering big stem villi compared with the trophoblast at other sites of the villous tree. In placentomes of a parturient cow, specific staining was only found in mature TGCs that survived the normal, but substantial, prepartal decline in TGC numbers. These results clearly showed that bovine UTCs and TGCs exhibit different steroidogenic capacities, constituting a 'two-cell' organisation for oestrogen synthesis. P450c17 expression appears to be quickly down-regulated and P450arom is up-regulated when UTCs enter the TGC differentiation pathway.
“…Both oestrone and oestradiol were detected in cotyledonary and caruncular tissues from about the fourth month of gestation (Tsumagari et al, 1993). This suggests that the placenta is able to produce oestrogens from as early as the first trimester.…”
Section: Oestrogen Productionmentioning
confidence: 94%
“…The foetal cotyledon is also the primary site of P450c17 and P450arom localization, the key enzymes for the synthesis of oestrogens (Tsumagari et al, 1993;Schuler et al, 2006a). P450c17 is present exclusively in the UTCs, but is down-regulated when these cells differentiate into TGCs; P450arom level, on the other hand, increases as UTCs differentiate to TGCs (Schuler et al, 2008).…”
Section: Compartmentalization Of Progesterone Synthesismentioning
confidence: 99%
“…P450c17 and P450arom enzymes are expressed mainly in cotyledonary trophoblast cells (Tsumagari et al, 1993;Schuler et al, 2006a). There are two times during gestation when P450c17 and P450arom activities increase significantly.…”
Section: Changes In Steroidogenic Activity Throughout Pregnancymentioning
SUMMARYSteroid hormones play critical roles in almost all physiological processes in male and female reproduction. In a normal pregnancy, the concentrations of steroid hormones in maternal and foetal blood vary with gestation in response to changing needs. The placenta plays a central role in producing the appropriate steroids to support the pregnancy by coordinating its own steroidogenic activity with that of the corpus luteum and responding to foetal signals. Although much is known about the steroidogenic potential of the bovine placenta, far less is known about how the placenta integrates the synthesis of steroids with their subsequent metabolism and clearance to achieve appropriate local and peripheral concentrations of steroids in maternal and foetal blood at each stage of gestation. This review focuses on the current knowledge of the temporal and spatial regulation and compartmentalization of the biochemical pathways by which potent steroid hormones are synthesized and metabolized in the bovine placenta. The aim is to increase our understanding of how the balance of synthesis and metabolism determines placental steroid output as it changes with development and differentiation, and how this is regulated in response to the variations in the foetal signals and luteal secretory activity. The review highlights knowledge gaps and suggests that mathematical modelling can help understand the effect of different levels of regulation on the steroidogenic output of an organ, such as the bovine placenta.
Placental oestrogens play an important role as local regulators of placental growth and differentiation during gestation, and toward term they are also involved in the preparation of parturition. They are synthesized within the fetal cotyledons of placentomes by aromatase cytochrome P450 (P450arom; EC 1.14.14.1), the product of the Cyp 19 gene. The first step of regulation of P450arom expression, and hence enzyme activity and oestrogen production, takes place at the level of Cyp 19 transcription, which is driven by a proximal promoter region, P1.5/2, in the sheep placenta. The aim of the present study was to find out if different Cyp 19 expression levels, which previously had been observed in ovine placentome tissues, correlate with the tissue-specific chromatin structure of the promoter. To this end, we investigated the chromatin structure across the P1.5/2 region in caruncles and cotyledons from 100 and 125 days pregnant ewes, and in term placentae, respectively, by analyzing the DNA methylation and the accessibility to restriction digestion. Our data show that: (1) cotyledonal DNA was significantly lower methylated than caruncular DNA; (2) methylation of cotyledonal DNA was low at 100 and 125 days of pregnancy, and increased to a significant higher level in term placentae; and (3) concurrently, cotyledonal chromatin became inaccessible to restriction digestion at term of gestation. The results imply that DNA methylation and chromatin accessibility of the P1.5/2 promoter region correlate with expression levels of the Cyp 19 gene.
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