Prostaglandin F 2a (PGF 2a ) released from the uterus causes alterations in luteal blood flow, reduces progesterone secretion, and induces luteolysis in the bovine corpus luteum (CL). We have recently discovered that luteal blood flow in the periphery of the mature CL acutely increases coincidently with pulsatile increases in a metabolite of PGF 2a (PGFM). In this study, we characterized changes in regional luteal blood flow together with regional alterations in endothelial nitric oxide synthase (eNOS) expression during spontaneous luteolysis and in response to PGF 2a . Smooth muscle actin-positive blood vessels larger than 20 mm were observed mainly in the periphery of mature CL. PGF 2a receptor was localized to luteal cells and large blood vessels in the periphery of mid-CL. PGF 2a acutely stimulated eNOS expression in the periphery but not in the center of mature CL. Injection of the NO donor S-nitroso-N-acetylpenicillamine into CL induced an acute increase in luteal blood flow and shortened the estrous cycle. In contrast, injection of the NOS inhibitor L-NAME into CL completely suppressed the acute increase in luteal blood flow induced by PGF 2a and delayed the onset of luteolysis. In conclusion, PGF 2a has a siterestricted action depending on not only luteal phase but also the region in the CL. PGF 2a stimulates eNOS expression, vasodilation of blood vessels, and increased luteal blood flow in periphery of mature CL. Furthermore, the increased blood flow is mediated by NO, suggesting that the acute increase in peripheral blood flow to CL is one of the first physiological indicators of NO action in response to PGF 2a .
Abstract. Administration of prostaglandin (PG) F2α in cattle during the mid-luteal phase (Days 8-12 of the estrous cycle) drastically reduces the plasma progesterone concentrations and the volume of the corpus luteum (CL). However, PGF2α does not induce luteolysis during the early luteal phase (up to Day 5 of the estrous cycle). To characterize the possible distinct difference in acute response to a luteolytic dose of PGF2α administration, we determined various mRNA expressions in the early and mid CL relating to angiogenesis, vasoactivation and PG-related factors at 30 min after PGF2α injection in cyclic cows. The experiments were conducted on Day 4 (early CL) and Days 10-12 (mid CL).Cows were either injected with 500 μg PGF2α analogue or saline as the control (early CL control, n=5; early CL PGF2α treated, n=5; mid CL control, n=5; mid CL PGF2α treated, n=7). Thirty min after injection of PGF2α or saline, the cows were ovariectomized transvaginally, and the CL tissues were collected from regions designated as the periphery and center of the CL. Administration of PGF2α up-regulated the mRNA expressions of angiogenic-related factors such as vascular endothelial growth factors, vasohibin, fibroblast growth factor 2 and insulin-like growth factor-II in the early CL, whereas PGF2α down-regulated these mRNA expressions in the mid CL. In the vasoactive factors, PGF2α stimulated the mRNA expressions of endothelin-1, angiotensin converting enzyme, endothelial nitric oxide synthase (NOS) and inducible NOS in the periphery area of the mid CL, but not in the early CL. However, PGF2α drastically down-regulated PGF2α receptor mRNA expression in both regions of the early and mid CL. The results indicated a clear difference in the acute action of PGF2α depending not only on the luteal phase (immature vs. mature) but also the region (periphery vs. center) within the CL at 30 min after PGF2α injection in the cow. Key words: Corpus luteum, Cow, Luteolysis, Prostaglandin F2α (J. Reprod. Dev. 56: [428][429][430][431][432][433][434][435][436] 2010) he corpus luteum (CL) is a transient endocrine organ in the ovaries of mammals. The bovine CL rapidly develops within 2-3 days after ovulation, which is accompanied by angiogenesis from the preovulatory follicle. The main function of the CL is to produce the progesterone (P) required for achievement and maintenance of pregnancy [1]. If the cow does not become pregnant, the CL is only functional for 17-18 days, and it must regress within a few days to induce the next chance for ovulation.In cows, it is well known that prostaglandin (PG) F2α from the uterus on days 17-18 of the estrous cycle is essential to induce regression of the CL [2]. In general, administration of PGF2α in the cow during the mid-luteal phase (Days 8-12 of the estrous cycle; mid CL) drastically reduces the plasma P concentration and volume of the CL. However, the same dose of PGF2α does not induce luteolysis during the early luteal phase (up to Day 5 of the estrous cycle; early CL) [3]. Recently, several studies hav...
Abstract. Cell-to-cell interaction via cell contact-dependent pathway is essentially important for maintenance and regulation of corpus luteum (CL) integrity and its physiological actions. The objective of the present study was to evaluate the mRNA expression of the cell adhesion molecules (CAMs) that are constituent factors of gap junctions [connexin (Cx) 43] and adherence junctions (VE-, E-, N-cadherin) in two types of endothelial cells from the mid CL and in CL tissue during the estrous cycle and PGF2α-induced luteolysis in the cow. Specific mRNA expression for Cx43 and N-cadherin was detected in cytokeratin-positive (CK+) and cytokeratin-negative (CK-) luteal endothelial cells (EC) and fully luteinized granulosa cells (LGC). E-cadherin mRNA was expressed in CK+EC andLGC, but not in CK-EC. VE-cadherin mRNA was expressed in both CK+ and CK-EC. During the estrous cycle, Cx43 mRNA expression was significantly lower in the regressing CL. VE-cadherin expression also tended to increase in the mid CL and increased significantly in the regressing CL. Ecadherin mRNA expression was higher in the early and late CL than in the mid-and regressing CL. N-cadherin mRNA expression gradually increased from the early to late CL followed by a decrease in the regressing CL. During PGF2α-induced luteolysis, Cx43 mRNA expression appeared to increase, and VE-cadherin and E-cadherin mRNA significantly increased at 24 h. N-cadherin mRNA expression decreased 2 and 4 h after PGF2α administration. Collectively, expression of the mRNAs for CAMs was different in the two types of luteal endothelial cells and fully luteinized granulosa cells and changed independently in the CL during the estrous cycle and PGF2α-induced luteolysis in the cow. The results suggest that CAMs play physiological roles in cell-to-cell communication to regulate both gap and adherence junctions during CL development and regression in the cow. Key words: Cadherin, Connexin, Corpus luteum, Cow, Luteolysis (J. Reprod. Dev. 53: [1319][1320][1321][1322][1323][1324][1325][1326][1327][1328] 2007) he corpus luteum (CL) is a transient organ that secretes progesterone (P), which is a prerequisite for establishment and maintenance of pregnancy. The CL is formed from the residual cells of a follicle after ovulation, in which cell growth and differentiation occur together with neoangiogenesis, and the CL acquires the capacity to secrete P. If pregnancy does not occur, prostaglandin (PG) F 2α is released from the uterus [1,2], and the CL rapidly looses its P secretory ability (functional luteolysis) [1,2]. Subsequently, its
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