Differences in Apoptotic Status in the Bovine Placentome between Spontaneous and Induced Parturition

Abstract

Abstract.We conducted this study to analyze apoptotic changes in the bovine placentome at spontaneous and induced parturition. Cows delivered i) after the administration of dexamethasone followed by prostaglandin F 2α and estriol, ii) after the administration of prostaglandin F 2α and estriol or iii) spontaneously. Prepartum changes in plasma progesterone and estradiol-17β concentrations were similar between spontaneous and induced parturition. Messenger RNA of BCL2-related protein A1 (BCL2A1), an antiapoptotic gene, was expressed by trophoblast binucleate cells and caruncular epithelial cells. Quantitative RT-PCR showed that the expression of BCL2A1 mRNA in cotyledonary and caruncular portions was significantly lower in spontaneous parturition than induced parturition. The expression of BCL2-associated X protein (BAX) mRNA, a proapoptotic gene, was significantly higher in cotyledons at spontaneous parturition than parturition induced without dexamethasone. Caspase-3 (CASP3) mRNA and pre-activated CASP3 protein were predominantly detected in caruncular epithelial cells regardless of how parturition proceeded. Activated CASP3 protein was found in trophoblast uninucleate cells and binucleate cells rather than caruncular epithelial cells. In spontaneous parturition, intense staining of activated CASP3 was detected in caruncular epithelial cells. Spontaneous and dexamethasone-induced parturition increased apoptotic cells in the placentome compared with parturition induced without dexamethasone. The number of binucleate cells was significantly decreased in spontaneous parturition. The present results suggest that although the clinical dose of dexamethasone induces apoptosis in the placentome at term, neither dexamethasone nor prostaglandin F 2α evoke normal physiological changes in the placentome during delivery such as a change in the balance of apoptosis-related genes and disappearance of binucleate cells. A ppropriate regulation of cell proliferation and regression in the placentome is essential to maintain and complete gestation. In the bovine placentome, the number of apoptotic cells increases as pregnancy progresses and is significantly high at around parturition [1,2]. The facilitation of apoptosis seems to reflect placental maturity during the peripartum period. Recent studies have shown that the status of apoptosis in the placentome correlates with the incidence of a retained placenta after parturition [1,3]. In addition, artificial induction of parturition by the administration of a glucocorticoid and/ or prostaglandin (PG) F 2α also frequently results in a retained placenta [4,5]. These findings suggest that apoptosis in the placentome is required for detachment of the fetal membrane in the early postpartum period, but apoptotic status and its control in the placentome around parturition are not fully understood.Most cells undergoing apoptosis execute the death program by activating a hierarchy of caspases [6]. In the murine placenta, apoptotic cells and the expression of caspase-3 (CASP3), one of the key ...

Bovine Fetal Placenta During Pregnancy and the Postpartum Period

“…These results are in agreement with another study describing a decline in the proliferation and an increase in cell death in maternal crypt epithelium, maternal stroma, and fetal chorionic epithelium during pregnancy and near parturition as physiological processes. 9 The same processes were observed by other authors 23 : they described the regulation of cell proliferation and regression as key for placental maturation during late pregnancy and for detachment of the fetal membrane in the early postpartum period. It was mentioned in another study that increased apoptosis is involved in placental maturation, 19 and similar results were found in the placentome of yaks.…”

“…This was followed by a semiquantitative analysis of these parameters by evaluation of the whole section. Cellular debris, inflammation, and mineralization were classified as mild (þ,n¼ 1-10 foci per section), moderate (þþ,n¼ [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30], and severe (þþþ,n¼ >30). Vasculitis was classified as mild (þ,n¼ 1-6), moderate (þþ,n¼ 7-12), and severe (þþþ,n¼ > 12).…”

Two treatment protocols for induction of preterm parturition in ewes—Evaluation of the effects on lung maturation and lamb survival

“…It has been shown that cows are at greater risk of retained foetal membranes following medical induction of parturition with an incidence of 19-53% (Lewing et al, 1985;Bo et al, 1992;Hirayama et al, 2012). There are inconsistent reports about this phenomenon in sheep.…”

Birth and death: Evidence for the same biologic clock

“…54 Placental apoptosis related to parturition has also been observed in non-human placental tissues. Hirayama et al 55 observed that apoptotic cells in bovine placentomes increase as pregnancy progresses, peaking at the time of parturition. These apoptotic events were associated with increased activated caspase-3, increased proapoptotic BAX expression, and decreased anti-apoptotic BCL2A1 expression.…”

“…These apoptotic events were associated with increased activated caspase-3, increased proapoptotic BAX expression, and decreased anti-apoptotic BCL2A1 expression. 55 In pregnant pigs, Cristofolini et al 56 described a 29-fold increase in the apoptosis index (as measured by TUNEL assay) in placental tissue from near-term pregnancies compared to those from mid-gestation.…”