Cell proliferation and apoptosis during development and aging of the rabbit corpus luteum

Corpora lutea (CL) are endocrine ovarian structures that regulate fundamental reproductive events in mammals. The functional lifespan of these structures is finite as CL regress and cease secreting progesterone after species-dependent intervals during nonfertile postovulatory cycles or pregnancy. The signals that regulate CL aging are poorly understood. This study investigates cell growth and programmed cell death or apoptosis in corpora lutea of New Zealand White rabbits. To study cell growth, CL were obtained at various postovulatory days (POD) from animals injected with the deoxyribonucleic acid (DNA) precursor analog bromodeoxyuridine (BUdR). The BUdR-labeled cells were identified by avidin-biotin-complex immunocytochemistry, and the mean proliferation index area computed by image analysis. Apoptotic cells were scored and further identified by in situ demonstration of DNA fragmentation. Proliferation in parenchymal, stromal, and endothelial CL cells was significantly elevated at POD 3, 5, 18, and 21 and highest at POD 3 (P < 0.001). The number of apoptotic cells was elevated (P < 0.001) at POD 18 and 21, while 1 percent or less of CL cells were apoptotic at POD 3, 5, and 12. Apoptosis was accompanied by shrinkage or vacuolization of CL cells and increased mean number (P < 0.001) of heterophilic leucocytes at POD 18. These data demonstrate that cell growth is more intense during early luteal development and that cell deletion via apoptosis plays an important role in CL regression. The role of paracrine signals such as microphagic cytokines in CL aging remains to be elucidated.