Angiogenesis in the human corpus luteum

Angiogenesis is important for the formation and development of the corpus luteum and for maintenance of luteal function. Blood vessel regression is an important physiological phenomenon in the corpus luteum, which is associated with tissue involution during structural luteolysis. Angiogenesis actively occurs during the early luteal phase and is completed by the mid-luteal phase. Perivascular cells (pericytes) increase in number from the early luteal phase to the mid-luteal phase, suggesting that blood vessels are gradually stabilized until the mid-luteal phase. In the corpus luteum undergoing luteolysis, blood vessels and pericytes decrease in number, which is related to structural involution. In the corpus luteum of early pregnancy, the number of blood vessels with pericytes increases, suggesting that angiogenesis occurs again, accompanied by blood vessel stabilization. These changes in vasculature of the corpus luteum are regulated by the collaboration with vascular endothelial growth factor, which is involved in proliferation of vascular endothelial cells, and angiopoietins, which are involved in stabilization of blood vessels. This review focuses on angiogenesis, blood vessel stabilization and blood vessel regression during the divergent phases of luteal formation, luteal regression and luteal rescue by pregnancy. (Reprod Med Biol 2008; 7 : 91–103)     

Extracellular matrix of the corpus luteum

The potential importance of the extracellular matrix to luteal formation and development, additional development in response to pregnancy hormones in some species, and luteal function and regression is possibly under-appreciated. Collagens I and III and fibronectin change dynamically during the formation of the corpus luteum and probably reflect the necessity for directional migration of cells in the establishment of a vascularized corpus luteum. Extracellular proteins may also be essential for the maintenance of luteal cell phenotype. Laminins, collagens type IV, and nidogen-1 have been localized to varying degrees of completeness in different species. Each capillary has a subendothelial basal lamina that changes in composition during luteal formation. These subendothelial basal laminas are often adjacent to luteal cells. The high vascularity of corpora lutea may have led to the assumption that luteal cells are surrounded by basal laminas. However, in rat, bovine, and human corpora lutea, there is no evidence of basal laminas surrounding luteal cells. Instead there are fibers or aggregates of basal lamina material rich in laminins interspersed throughout the luteal tissue. Versican appears to be localized to the capsule in human corpora lutea but is widely dispersed in the bovine corpus luteum, similar to the distribution of thecal derived cells, and is not associated with capillaries. Hyaluronan is also present in the luteal parenchyma. Clearly more studies of corpora lutea are required for a fuller understanding of the roles of extracellular matrix in luteal function.     

The role of nitric oxide in apoptosis

Nitric oxide (NO) has been shown to play important roles in modulating cell viability. Both proapoptotic and antiapoptotic functions of NO have been reported. This article discusses our current understanding on the mechanisms responsible for the dual actions of NO in regulating apoptosis and propose that one common mechanism for NO-mediated inhibition of apoptosis is the inhibition of caspases via nitrosylation.     

Prostaglandin and the corpus luteum of pregnancy

Prostaglandins can cause pregnancy to be terminated through any of the following mechanisms: 1) direct luteolytic effect of prostaglandins on early pregnancy; 2) intense myometrial disloding and expelling of the embryo; 3) indirect luteolytic effect caused by the removal of possible luteotropical support of the conceptus due to direct action of prostaglandin; and 4) direct interference of prostaglandin on early placental production of progesterone and other hormones. The present study was conducted to determine the histopathological changes in the corpora lutea taken out during abdominal tubal ligation of 30 women within 1 to 4 hours after abortion. 15-methyl PGF2a was administered through extraovular route in 15 cases; 15 control cases had hysterectomy and tubal ligation, and ovarian biopsy by abdominal route. Macroscopically, the corpora lutea of the experimental cases appeared congested and at times, hemorrhagic; most had clots in the cavity. The ovaries appeared normal and comparable to those of the controls. The rectus sheath, uterus and fallopian tubes exhibited vascular congestion. Microscopically, the granulosa lutein cell of the experimental group seemed either irregular or indistinct, with the cytoplasm exhibiting a large number of vacuolation, and the nuclei showing Pyknotic, karyorrhetic or karyopyknotic changes. It was suggested that the degenerative changes in the corpora lutea were due to the prostaglandins' lowering of the level of progesterone and the termination of early pregnancy.     

一氧化氮及一氧化氮合酶与卵巢肿瘤凋亡的关系

目的探讨卵巢良、恶性肿瘤患者血清、肿瘤组织、腹水中一氧化氮(nitricoxide,NO)及其合酶(nitricoxidesynthase,NOS)含量与肿瘤凋亡的关系。方法用分光光度计测定NO、NOS、iNOS活性,流式细胞仪检测细胞凋亡。结果恶性卵巢肿瘤患者血清、肿瘤组织中NO、NOS、iNOS高于良性肿瘤患者(P<0.05);腹水或腹腔冲洗液中iNOS亦高于良性(P<0.05),但腹水中NO、NOS与良性无差异(P>0.05)。恶性肿瘤细胞凋亡率高于良性(P<0.05)。结论NO、NOS、iNOS与卵巢肿瘤的恶性行为及凋亡有关,检测患者血清、组织、腹水中的NO、NOS、iNOS对鉴别良、恶性肿瘤有一定参考价值,可作为观测卵巢癌疗效及预后的指标。     

Studies of the human corpus luteum: Evidence for the early onset of regression of the corpus luteum of menstruation

The subject of this report is concerned with the time at which regression begins in the corpus luteum of menstruation.The life cycle of the corpus luteum of menstruation in the human being has been described and its division into four typical stages has been universally accepted. These stages are termed proliferation, vascularization, mature or blossom stage, and stage of regression (Meyer, 1911; Frank, 1914). Meyer, 1911, Meyer, 1932 observed that the blossom and regression stages were imperfectly limited and stated that the beginning of regression could not be definitely recognized. Novak (1934 and 1941) stated that regression begins shortly before the onset of menstruation, about the twenty-sixth day in a patient with a twenty-eight-day ovulatory cycle. The material to be presented here indicates rather that regression begins at the termination of the so-called vascularization stage, four to six days before the onset of menstruation.In order to avoid confusion, I wish to state that I shall not describe the reported specimens in relation to days of the menstrual cycle. The variability in the length of normal cycles is so great that the dating of specimens according to this method may lead to confusion. Since that portion of the menstrual cycle between the time of ovulation and the onset of menstruation is relatively constant, I shall date all specimens by the probable days of age of the corpus luteum. Exact age of a given corpus luteum is difficult to determine. Histologic characteristics offer the best method. It is possible to evaluate the approximate age within two to three days by these histologic characteristics. For the most exact age determinations, it is necessary to study a series of specimens in this report. By this method of comparison the age of an individual specimen can be estimated more accurately. The study of the normal endometrium is also an aid in making age determinations of corpora lutea.     

New aspects concerning the corpus luteum]

We have summed up current knowledge about the formation and lysis of corpus luteum with the co-ordinate intervention of luteotrophic and luteolytic factors. Then we re-examined the function of the corpus luteum in the physiologic menstrual cycle and in the first period of pregnancy, with special attention to luteal insufficiency as a cause of endocrine miscarriage.     

Experimental aspects of corpus luteum function

In surveying current research on the corpus luteun it becomes very clear that some of the greatest steps forward have come from studies on the formation of this organ. At one time, follicular rupture, the maturation and extrusion of the oocyte, and the luteinization of the granulosal cell layer inside the follicle all appeared to be parts of a sequential process. Now it emerges that these processes are individual in character and that separate actions of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) can be recognized.