Growth and Regression in Bovine Corpora Lutea: Regulation by Local Survival and Death Pathways

Abstract

ContentsThe bovine corpus luteum (CL) is a transient gland with a life span of only 18 days in the cyclic cow. Mechanisms controlling CL development and secretory function may involve factors produced both within and outside this gland. Although luteinizing hormone (LH) surge is the main trigger of ovulation and granulosa cells luteinization, many locally produced agents such as arachidonic acid (AA) metabolites, growth factors and cytokines were shown to complement gonadotropins action in the process of CL development. Bovine CL is a highly vascular gland, where the very rapid angiogenesis rate (until Day 5 of the cycle) results in the development of a capillary network, endowing this gland with one of the highest blood flow rate per unit mass in the body. Angiogenesis in the developing CL is later followed by either controlled regression of the microvascular tree in the nonfertile cycle or maintenance and stabilization of the blood vessels, as seen during pregnancy. Different luteal cell types (both steroidogenic and accessory luteal cells: immune cells, endothelial cells, pericytes and fibroblasts) are involved in the pro-and/or anti-angiogenic responses. The balance between pro-and anti-angiogenic responses to the main luteolysin -prostaglandin F2a (PGF2a) could be decisive in whether or not PGF2a induces CL regression. Fibroblast growth factor-2 (FGF2) may be one of the factors that modulate the angiogenic response to PGF2a. Manipulation of local production and action of FGF2 will provide new tools for reproductive management of dairy cattle. Luteolysis is characterized by a rapid decrease in progesterone production, followed by structural regression. Factors like endothelin-1, cytokines (tumour necrosis factora, interferons) and nitric oxide were all shown to play critical roles in functional and structural regression of the CL by inhibiting steroidogenesis and inducting apoptosis.

Programmed necrosis - a new mechanism of steroidogenic luteal cell death and elimination during luteolysis in cows

“…In the present study, PGF did not affect RIPKs mRNA expression in a pure population of cultured LSCs. Therefore, it could be concluded that the luteolytic action of PGF on bovine CL in vivo is mediated by several auto/paracrine factors which activate luteolytic mechanisms responsible for structural and functional luteal regression38. Similarly, the effect of PGF on RIPKs expression might depend on some mediators or upon cell composition and contact.…”

Effects of IL8 and immune cells on the regulation of luteal progesterone secretion

“…These observations support our earlier findings (Liptak et al 2005) that activated immune cells may contribute a factor (or factors) that impair steroidogenesis in response to LH. It is known that activated monocytes produce inflammatory cytokines, nitric oxide, and reactive oxygen species (Murray & Wynn 2011, Zhou et al 2014) all of which may contribute individually or in combination to the inhibition of progesterone synthesis (Al-Gubory et al 2012, Quirk et al 2013, Skarzynski et al 2013). In the in vivo setting, activated monocytes may also secrete matrix metalloproteinases that contribute to the degradation of the extracellular matrix (Murray & Wynn 2011), which could facilitate the recruitment of additional inflammatory cells to the regressing corpus luteum.…”

Expression and localization of cFLIP anti-apoptotic protein in the porcine corpus luteum and corpora albicans during the estrous cycle and pregnancy

“…Structural luteolysis (destruction and removal of the luteal cells) is also required to keep the ovary in proper proportion to the rest of the reproductive tract (Skarzynski et al, 2013). Luteolysis is defined as the loss of function and subsequent involution of the luteal structure.…”