Excess estrogen sulfoconjugation as the possible cause for a poor sign of parturition in pregnant cows carrying somatic cell clone fetuses

Abstract

We conducted this study to elucidate a factor causing a poor sign of parturition and prolonged gestation, which is frequently observed in cows carrying somatic clone fetuses. Pre-partum rises in concentrations of plasma estrone and estradiol-17b in the recipient cows pregnant with clones were subtle. By contrast, the plasma concentration of estrone sulfate in clone pregnancies increased gradually from pre-initiation of parturition induction whereas control cows that received in vivo-derived embryos showed a significant increase at parturition. Therefore, in clone pregnancies, the ratio of estrone/estrone sulfate was low during the pre-partum period compared with control. Messenger RNA expression of estrogen sulfotransferase (SULT1E1) in the placenta at parturition was significantly higher in clone pregnancies than control pregnancies and was localized in binucleate cells (BNC). SULT1E1 mRNA abundance was negatively and positively correlated with concentrations of maternal estrone and estrone sulfate at parturition respectively. Messenger RNA expressions of estrogen sulfatase (STS) and aromatase (CYP19) were similar between clone and control pregnancies and were localized in BNC and caruncular epithelial cells. STS and CYP19 mRNA abundances showed positive correlations with maternal estradiol-17b concentration. The population of BNC in the placenta did not differ between clone and control pregnancies. Plasma cortisol concentration of vaginally delivered newborn clone calves was comparable with those of control, although cesarean section delivered clone calves showed a low concentration. These results suggest that excess estrogen sulfoconjugation is the reason for the perturbed low ratio of active to inactive estrogens and the resulting hormonal imbalance contributes to the lack of overt signs of readiness for parturition in cows pregnant with clones.

Plasma estrone sulfate, clinical biochemistry, and milk yield of dairy cows carrying a fetus from a bull or its clone

“…The lack of a significant difference among CBW group for the gestation length was probably due to low number of observations in the trial; however, the numerical scale and the result from the contrast BWT-A, BWT-B versus BWT-C is consistent with the discussion of Hirayama et al [18] about the effect of sulfoconjugation and the signs of parturition.…”

“…Second, however, we must consider that both groups of pregnancies were derived from IVPE system, and this could be another variable that has a greater effect on CBW than the origin of the bull [19]. We are not aware of a possible effect of IVPE system per se on the expression of estrogen sulfotransferase (SULT1E1), which could be affected by cloning as reported in the article by Hirayama et al [18]; however, their comparison was done with in vivo-fertilized embryos rather than in vitro. Therefore, it is not possible to conclude, if alteration of parturition is due to the clonal origin or the large offspring syndrome, that it is also described, albeit at much lower frequency, for pregnancies from IVPEs.…”

“…This is especially true for the changes in the estrogen plasma concentration in the last weeks of pregnancy. In a specific study on dairy cows carrying cloned or control fetuses, Hirayama et al [18] monitored sexual hormones in late pregnancy. They evidenced how an excessive sulfoconjugation of estrogen (reflected in the plasma ratio between estrone and its conjugated form) could be at the origin of a poor signal for parturition in the cow, thus leading to some abnormalities in the regulation of calving.…”

Prepartum Maternal Plasma Glucose Concentrations and Placental Glucose Transporter mRNA Expression in Cows Carrying Somatic Cell Clone Fetuses

“…These findings imply that disruption of cortisol secretion in clone fetuses is a principal cause of the problems in the peripartum period. Chavatte-Palmer et al [3] reported that the responsiveness of the adrenocortical tissue to adrenocorticotrophin in clone calves is normal, and we have also shown that clone calves had the ability to secrete cortisol at parturition [9]. However, the secretion of cortisol in prepartum clone fetuses is not fully understood.…”

“…Furthermore, cortisol downregulates fetal growth and stimulates the maturation of those organs essential for extrauterine survival, such as the lungs and thyroid [8]. Previously, we reported an insufficient increase of the prepartum estrogen concentration in pregnant cows carrying a clone fetus [9]. LOS and respiratory distress syndrome are also frequently observed in neonatal clone calves [2].…”