The Molecular Control of Corpus Luteum Formation, Function, and Regression

Abstract

The corpus luteum (CL) is one of the few endocrine glands that forms from the remains of another organ and whose function and survival are limited in scope and time. The CL is the site of rapid remodeling, growth, differentiation, and death of cells originating from granulosa, theca, capillaries, and fibroblasts. The apparent raison d'etre of the CL is the production of progesterone, and all the structural and functional features of this gland are geared toward this end. Because of its unique importance for successful pregnancies, the mammals have evolved a complex series of checks and balances that maintains progesterone at appropriate levels throughout gestation. The formation, maintenance, regression, and steroidogenesis of the CL are among the most significant and closely regulated events in mammalian reproduction. During pregnancy, the fate of the CL depends on the interplay of ovarian, pituitary, and placental regulators. At the end of its life span, the CL undergoes a process of regression leading to its disappearance from the ovary and allowing the initiation of a new cycle. The generation of transgenic, knockout and knockin mice and the development of innovative technologies have revealed a novel role of several molecules in the reprogramming of granulosa cells into luteal cells and in the hormonal and molecular control of the function and demise of the CL. The current review highlights our knowledge on these key molecular events in rodents.

Aromatase expression in the ovary: Hormonal and molecular regulation

“…During the first week of pregnancy, corpus luteum function is maintained by the actions of prolactin (PRL) and LH [89]. Prolactin is secreted from the pituitary gland until approximately days 9−10 of gestation [90].…”

A simple mathematical model of the bovine estrous cycle: Follicle development and endocrine interactions

“…The dominant follicle that is present at the onset of CL regression becomes the ovulatory follicle [3,6]. In the preovulatory follicle, the LH peak induces a shift from E2 to P4 production [18] by changing the expression of steroidogenic enzymes [6,72]. Follicle development is modeled as growth of E2 and Inh producing tissue.…”

Five different phenotypes of endothelial cell cultures from the bovine corpus luteum: Present outcome and role of potential dendritic cells in luteolysis

“…Capillaries are also a powerful paracrine factory for the production of growth factors and chemokines, and capillaries are the site for leukocyte recruitment (Stocco et al, 2007;Devoto et al 2009). Inspite of the 40% of vascular cells in a CL, the isolation of endothelial cells using enzyme digestion of CL tissue or lectin-coated-magnetic beads often fails to obtain persistent protein expression in long-term culture (Acosta et al, 2005).…”

“…Monocytes and increasing numbers of T cells with dominance of cytotoxic T cells must be recruited before the decay of capillaries and the fatty degeneration of luteal cells (Brännström et al, A c c e p t e d M a n u s c r i p t 12 structural luteolysis becomes evident (Stocco et al, 2007;Devoto et al, 2009). The scenario could be triggered by sudden ischemia due to vasoconstriction by e.g.…”

“…Time has provided tremendous progress in understanding the molecular pattern of luteolysis and the function of INIM in sterile inflammation like in atherosclerosis and rheumatoid arthritis (Stocco et al, 2007;Devoto et al, 2009;Medzhitov, 2008Medzhitov, , 2010.…”