Endocrine, Paracrine, and Autocrine Signaling Pathways That Regulate Ovulation

Ovulation is triggered when the ovulatory surge of LH activates the LHCGR in the mural granulosa cells of the ovarian follicle. This initial signal is propagated to the cumulus cells and the oocyte through paracrine and autocrine signaling pathways that result in the release of a fertilizable oocyte. The ovarian EGFR network and the ERK1/2 cascade, two pathways that are traditionally associated with cell proliferation, are activated by the LHCGR and are involved in (EGFR network) or essential to (ERK1/2) the ovulatory response. The signaling pathways that participate in ovulation provide an example of how the activation of a single receptor (LHCGR) in a single cell type results in the vectorial transfer of information among other cell types that do not express the receptor. The central role of luteinizing hormone (LH) and its receptor (LHCGR) in triggering ovulation has been recognized for decades. Because the LHCGR is present in the mural (outermost) granulosa cell layer of preovulatory follicles (POFs), the LH-initiated signal has to be transmitted to another somatic cell type (cumulus granulosa cells) and the oocyte to release a fertilizable oocyte. Recent studies have shown that activation of the LHCGR initiates vectorial transfer of information among the two somatic cell types and the oocyte and the molecules and signaling pathways involved are now better understood. This review summarizes the newer developments on the complex signaling pathways that regulate ovulation. The central role of luteinizing hormone (LH) and its receptor (LHCGR) in triggering ovulation has been recognized for decades. Because the LHCGR is present in the mural (outermost) granulosa cell layer of preovulatory follicles (POFs), the LH-initiated signal has to be transmitted to another somatic cell type (cumulus granulosa cells) and the oocyte to release a fertilizable oocyte. Recent studies have shown that activation of the LHCGR initiates vectorial transfer of information among the two somatic cell types and the oocyte and the molecules and signaling pathways involved are now better understood. This review summarizes the newer developments on the complex signaling pathways that regulate ovulation. the two types of somatic cells inside the basal lamina of the ovarian follicle that participate in the ovulatory response. The term granulosa cell is often used to denote mural granulosa cells whereas cumulus granulosa cells are often referred to simply as cumulus. experimentally assessed microscopically by examining the thickness of the cumulus layer in ovarian slices, isolated follicles, or cumulus oocyte complexes (COCs) extruded from ovarian follicles. It can also be assessed by measuring the increased expression of several ovarian ‘cumulus expansion genes’, such as Has2, Pgts2, and Tnfaip6. oocytes present in the POF are arrested in meiotic prophase, characterized by the presence of a large nucleus (also known as the germinal vesicle) with a prominent nucleolus. The first meiotic division is triggered by activation of the LHCGR and is characterized by breakdown of the nuclear envelope (also known as germinal vesicle breakdown) and the segregation of chromosomes to produce a haploid gamete. Meiosis is arrested again at the second metaphase and the ovulated oocyte remains at this stage until fertilization occurs. experimentally assessed microscopically in ovarian sections at a time after ovulation should have occurred. If follicles have not ruptured, mature oocytes (without a germinal vesicle) are trapped in unruptured follicles or in corpora lutea. Corpora lutea are the ovarian structures (comprising mostly luteinized mural granulosa cells) that arise from follicles after ovulation. all of the events triggered by activation of the LHCGR in a POF that lead to the release of a fertilizable oocyte. The ovulated oocytes are released as COCs (i.e., oocytes surrounded by a few layers of cumulus cells) rather than denuded. Ovulation occurs cyclically in mature mice but ovarian follicular growth and maturation of the follicle to the preovulatory stage can be induced in prepubertal female mice by injecting them with pregnant mare serum gonadotropin, a surrogate for follicle-stimulating hormone, the pituitary hormone that elicits follicular growth and maturation. Ovulation is then generally induced 2 days later by injecting these mice with hCG, a surrogate for luteinizing hormone, the endogenous pituitary hormone that triggers ovulation. This protocol is often referred to as ‘superovulation’ and is particularly useful when examining the reproductive phenotype of mice with targeted but global gene inactivation (or spontaneous germline inactivating mutations) because it eliminates the possible impact of gene inactivation in extraovarian tissues. experimentally assessed microscopically by the presence of oocytes without a germinal vesicle in ovarian sections, isolated follicles, or COCs extruded from ovarian follicles. It can also be triggered in vitro by adding hCG to POFs or by increasing cAMP levels in COCs by pharmacological stimulation of adenylyl cyclase or inhibition of cGMP phosphodiesterases.