Corpus Luteum Development: Lessons from Genetic Models in Mice
Introduction
The corpus luteum (CL) is an endocrine gland of limited life span formed from the remaining granulosa and theca cells of the follicle after ovulation. The corpus luteum produces progesterone and, in the event of fertilization, provides the required progesterone responsible for preparing the uterus for pregnancy and, if pregnancy occurs, maintaining it until birth in rodents. It inhibits the contractile activity of the uterus and inhibits development of a new follicle. The corpus luteum also produces low amounts of estrogen. In the absence of fertilization, the life span of the corpus luteum is limited. In rodents, the corpus luteum exerts an essential role, because it is responsible for the maintenance of full pregnancy by sustaining progesterone secretion, whereas in humans it provides the required progesterone until the placenta is formed. After ovulation on the morning of estrus, the corpus luteum secretes a limited amount of progesterone, is maintained 2 days, and then involutes if mating does not occur. On estrus, mating induces the release of prolactin (PRL) from the anterior pituitary by activation of a neural network that begins at the cervix and ends in the hypothalamus (Freeman et al., 2000). This causes two daily surges of PRL to be released for 12 days (Freeman 1972, Morishige 1973); if fertilization does not occur, the corpus luteum survives then establishing the pseudopregnancy state.
Section snippets
Development of the Corpus Luteum
The preovulatory surge of gonadotrophins induces ovulation and differentiation of residual follicular cells that form the corpus luteum and begin to produce progesterone at high levels. Before this step, granulosa and theca cells of the follicle produce estrogens. Theca cells express the enzymes necessary to convert cholesterol to androgens, whereas granulosa cells can convert androgens to estradiol. Thus, androgens produced by theca cells are aromatized to estradiol by granulosa cells.
Luteolysis
Luteinized cells complete their life span by a process of structural luteolysis that includes cell fusion, apoptosis, and phagocytosis. Luteolysis is characterized by an initial decline of progesterone secretion that is commonly designated as functional luteolysis as distinct from structural luteolysis, which signifies the subsequent change in the cellular structure of the gland and its gradual involution in the ovary to form a small scar composed of connective tissue. This latter structure,
Factors Affecting the Maintenance or the Development of the Corpus Luteum: Mouse Models
One of the most important advances in the study of mammalian genes has been the development of techniques to obtain defined mutations in mice. Often, the deletion of a gene that has accepted functions from biochemical and cell biological experiments results in different kinds of phenotypes. Frequently, this takes the form of no or mild phenotypes and evokes the possibility that redundantly functioning genes exist. Efforts to define the functions of PRL and its receptor from the phenotype of
Conclusion
This chapter has reviewed the advances in our understanding of corpus luteum function that have been greatly facilitated by the analysis of many mutant mice. Targeted mutagenesis models are increasingly being used to study reproductive function and also to understand fundamental processes of development. The mechanisms by which the progesterone required for establishment and maintenance of pregnancy are regulated by the mammalian conceptus. In all cases, adequate luteal progesterone is secreted
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