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Physiological Reviews Jan 2000The primary function of the corpus luteum is secretion of the hormone progesterone, which is required for maintenance of normal pregnancy in mammals. The corpus luteum... (Review)
Review
The primary function of the corpus luteum is secretion of the hormone progesterone, which is required for maintenance of normal pregnancy in mammals. The corpus luteum develops from residual follicular granulosal and thecal cells after ovulation. Luteinizing hormone (LH) from the anterior pituitary is important for normal development and function of the corpus luteum in most mammals, although growth hormone, prolactin, and estradiol also play a role in several species. The mature corpus luteum is composed of at least two steroidogenic cell types based on morphological and biochemical criteria and on the follicular source of origin. Small luteal cells appear to be of thecal cell origin and respond to LH with increased secretion of progesterone. LH directly stimulates the secretion of progesterone from small luteal cells via activation of the protein kinase A second messenger pathway. Large luteal cells are of granulosal cell origin and contain receptors for PGF(2alpha) and appear to mediate the luteolytic actions of this hormone. If pregnancy does not occur, the corpus luteum must regress to allow follicular growth and ovulation and the reproductive cycle begins again. Luteal regression is initiated by PGF(2alpha) of uterine origin in most subprimate species. The role played by PGF(2alpha) in primates remains controversial. In primates, if PGF(2alpha) plays a role in luteolysis, it appears to be of ovarian origin. The antisteroidogenic effects of PGF(2alpha) appear to be mediated by the protein kinase C second messenger pathway, whereas loss of luteal cells appears to follow an influx of calcium, activation of endonucleases, and an apoptotic form of cell death. If the female becomes pregnant, continued secretion of progesterone from the corpus luteum is required to provide an appropriate uterine environment for maintenance of pregnancy. The mechanisms whereby the pregnant uterus signals the corpus luteum that a conceptus is present varies from secretion of a chorionic gonadotropin (primates and equids), to secretion of an antiluteolytic factor (domestic ruminants), and to a neuroendocrine reflex arc that modifies the secretory patterns of hormones from the anterior pituitary (most rodents).
Topics: Animals; Corpus Luteum; Estrogens; Female; Humans; Mammals; Pituitary Gland, Anterior; Pituitary Hormones, Anterior; Pregnancy; Progesterone
PubMed: 10617764
DOI: 10.1152/physrev.2000.80.1.1 -
Fertility and Sterility Apr 2012To evaluate whether unacylated ghrelin and obestatin were able to influence human luteal cell function. The effect of these two ghrelin-related peptides on progesterone...
OBJECTIVE
To evaluate whether unacylated ghrelin and obestatin were able to influence human luteal cell function. The effect of these two ghrelin-related peptides on progesterone (P4), prostaglandin (PG) F(2α), PGE(2), and vascular endothelial growth factor (VEGF) release and on VEGF expression in isolated human steroidogenic cells has been investigated.
DESIGN
Prospective laboratory study.
SETTING
University hospital.
PATIENT(S)
Corpora lutea were obtained from 23 normally menstruating patients in the midluteal phase of the menstrual cycle.
INTERVENTION(S)
Human luteal cells were isolated from corpora lutea, and primary cultures were established.
MAIN OUTCOME MEASURE(S)
P4 and PGs release was assayed by enzyme immunoassay, VEGF secretion by ELISA, and VEGF mRNA expression by real-time polymerase chain reaction.
RESULT(S)
P4 and VEGF release were significantly reduced by both unacylated ghrelin and obestatin. Moreover, the highest concentration of obestatin was able to reduce the release of PGE(2) and PGF(2α). VEGF mRNA expression was not affected by the incubation with any of these ghrelin-related peptides. As expected, CoCl(2) was able to induce VEGF release and mRNA expression in luteal cells.
CONCLUSION(S)
Our results suggest that, similar to ghrelin, both unacylated ghrelin and obestatin might play a role in regulating the luteal cell function that affects both luteal steroidogenesis and luteotrophic/luteolytic imbalance. These results further underline the pivotal correlation between the ghrelin system and reproduction.
Topics: Acylation; Adult; Cells, Cultured; Cobalt; Dinoprost; Enzyme-Linked Immunosorbent Assay; Female; Ghrelin; Humans; Luteal Cells; Progesterone; RNA, Messenger; Real-Time Polymerase Chain Reaction; Vascular Endothelial Growth Factor A
PubMed: 22285751
DOI: 10.1016/j.fertnstert.2012.01.096 -
Animals : An Open Access Journal From... Feb 2020The main reproductive organs undergo different histological appearances and physiological processes under different reproductive statuses. The variation of these organs...
The main reproductive organs undergo different histological appearances and physiological processes under different reproductive statuses. The variation of these organs depends on a delicate regulation of cell proliferation, differentiation, and apoptosis. Extracellular signal-regulated kinases1/2 (ERK1/2) are members of the mitogen-activated protein kinase (MAPK) super family. They have important roles in regulating various biological processes of different cells, tissues, and organ types. Activated ERK1/2 generally promotes cell survival, but under certain conditions, ERK1/2 also have the function of inducing apoptosis. It is widely believed that ERK1/2 play a significant role in regulating the reproductive processes of mammals. The goal of our research is to investigate the expression and distribution of ERK1/2 in the yak's main reproductive organs during different stages. In the present study, samples of the ovary, oviduct, and uterus of 15 adult female yak were collected and used in the experiment. The ERK1/2 proteins, localization, and quantitative expression of their mRNA were investigated using immunohistochemistry (IHC), western blot (WB) and relative quantitative real-time polymerase chain reaction (RT-PCR). The results indicated that ERK1/2 proteins and their mRNA were highly expressed in the ovary of the luteal phase and gestation period, in the oviduct of the luteal phase, and in the uterus of the luteal phase and gestation period. Immunohistochemical analysis revealed a strong distribution of ERK1/2 proteins in follicular granulosa cells, granular luteal cells, villous epithelial cells of the oviduct, endometrial glandular epithelium, and luminal epithelium. These results demonstrated that the expression of ERK1 and ERK2 proteins and their mRNA in the yak's ovary, oviduct, and uterus varies with the stage of the reproductive cycle. The variation character of ERK1 and ERK 2 expression in the yak's main reproductive organs during different stages implies that they play an important role in regulating the reproductive function under different physiological statuses.
PubMed: 32093255
DOI: 10.3390/ani10020334 -
Life Science Alliance Oct 2023Estradiol and progesterone are the primary sex steroids produced by the ovary. Upon luteinizing hormone surge, estradiol-producing granulosa cells convert into...
Estradiol and progesterone are the primary sex steroids produced by the ovary. Upon luteinizing hormone surge, estradiol-producing granulosa cells convert into progesterone-producing cells and eventually become large luteal cells of the corpus luteum. Signaling pathways and transcription factors involved in the cessation of estradiol and simultaneous stimulation of progesterone production in granulosa cells are not clearly understood. Here, we decipher that phosphorylated ERK1/2 regulates granulosa cell steroidogenesis by inhibiting estradiol and inducing progesterone production. Down-regulation of transcription factor FOXL2 and up-regulation of SOX9 by ERK underpin its differential steroidogenic function. Interestingly, the incidence of SOX9 is largely uncovered in ovarian cells and is found to regulate FOXL2 along with CYP19A1 and STAR genes, encoding rate-limiting enzymes of steroidogenesis, in cultured granulosa cells. We propose that the novel ERK1/2-SOX9/FOXL2 axis in granulosa cells is a critical regulator of ovarian steroidogenesis and may be considered when addressing pathophysiologies associated with inappropriate steroid production and infertility in humans and animals.
Topics: Female; Humans; Animals; Ovary; Progesterone; MAP Kinase Signaling System; Corpus Luteum; Estradiol; Forkhead Box Protein L2; SOX9 Transcription Factor
PubMed: 37532283
DOI: 10.26508/lsa.202302100 -
Molecular and Cellular Endocrinology Jan 2017After ovulation, somatic cells of the ovarian follicle (theca and granulosa cells) become the small and large luteal cells of the corpus luteum. Aside from known cell...
After ovulation, somatic cells of the ovarian follicle (theca and granulosa cells) become the small and large luteal cells of the corpus luteum. Aside from known cell type-specific receptors and steroidogenic enzymes, little is known about the differences in the gene expression profiles of these four cell types. Analysis of the RNA present in each bovine cell type using Affymetrix microarrays yielded new cell-specific genetic markers, functional insight into the behavior of each cell type via Gene Ontology Annotations and Ingenuity Pathway Analysis, and evidence of small and large luteal cell lineages using Principle Component Analysis. Enriched expression of select genes for each cell type was validated by qPCR. This expression analysis offers insight into cell-specific behaviors and the differentiation process that transforms somatic follicular cells into luteal cells.
Topics: Animals; Biomarkers; Cattle; Cell Lineage; Cluster Analysis; Female; Gene Expression Profiling; Gene Expression Regulation; Granulosa Cells; Luteal Cells; Luteinization; Microarray Analysis; Ovarian Follicle; Principal Component Analysis; Reproducibility of Results; Theca Cells; Transcriptome
PubMed: 27693538
DOI: 10.1016/j.mce.2016.09.029 -
Oxidative Medicine and Cellular... 2021The increase of oxidative stress is one of the important characteristics of mammalian luteal regression. Previous investigations have revealed the essential role of...
The increase of oxidative stress is one of the important characteristics of mammalian luteal regression. Previous investigations have revealed the essential role of reactive oxygen species (ROS) in luteal cell death during luteolysis, while it is unknown how ROS is regulated in this process. Considering the decrease of blood flow and increase of PGF during luteolysis, we hypothesized that the HIF-1 pathway may be involved in the regulation of ROS in the luteal cell of the late corpus luteum (CL). Here, by using a pseudopregnant rat model, we showed that the level of both HIF-1 and its downstream BNIP3 was increased during luteal regression. Consistently, we observed the increase of autophagy level during luteolysis, which is regulated in a Beclin1-independent manner. Comparing with early (Day 7 of pseudopregnancy) and middle CL (Day 14), the level of ROS was significantly increased in late CL, indicating the contribution of oxidative stress in luteolysis. Inhibition of HIF-1 by echinomycin (Ech), a potent HIF-1 inhibitor, ameliorated the upregulation of BNIP3 and NIX, as well as the induction of autophagy and the accumulation of ROS in luteal cells on Day 21 of pseudopregnancy. Morphologically, Ech treatment delayed the atrophy of the luteal structure at the late-luteal stage. An in vitro study indicated that inhibition of HIF-1 can also attenuate PGF -induced ROS and luteal cell apoptosis. Furthermore, the decrease of cell apoptosis can also be observed by ROS inhibition under PGF treatment. Taken together, our results indicated that HIF-1 signaling is involved in the regression of CL by modulating ROS production via orchestrating autophagy. Inhibition of HIF-1 could obviously hamper the apoptosis of luteal cells and the process of luteal regression.
Topics: Animals; Corpus Luteum; Female; Hypoxia-Inducible Factor 1, alpha Subunit; Luteolysis; Pregnancy; Pseudopregnancy; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species
PubMed: 34512862
DOI: 10.1155/2021/1764929 -
Cell & Developmental Biology 2017The mechanistic events of female infertility have been investigated for over 50 years and despite progress many causes of infertility remain elusive. However, over half...
The mechanistic events of female infertility have been investigated for over 50 years and despite progress many causes of infertility remain elusive. However, over half of idiopathic infertility issues have been attributed to a defective ovarian tissue responsible for the maintenance of a conceptus, the corpus luteum (CL). Many CL defects are attributed, in part, to abnormal vascularization (angiogenesis), which occurs primarily during the developmental stage of the luteal lifespan. A few well-established angiogenic growth promotants have been implicated in luteal angiogenic processes but the mechanisms of the process are still under investigation. Recent evidence supports a role for the adipokine hormone leptin as a probable component in the angiogenic and developmental processes of a CL. Leptin expression is present during the developmental and maturation stages of the luteal lifespan and stimulates the expression of angiogenic hormones in the CL. Induced leptin deficient CL have a higher occurrence of abnormal, underdeveloped gross morphology and an increase in the number of large diameter vessels and large luteal cells. Leptin replacement therapy in leptin deficient CL accelerates tissue development, increasing overall tissue mass and forming a structure that resembled a mature CL during the early stages of development. Collectively, the evidence supports the supposition that leptin is involved in the angiogenic and developmental processes of luteal tissue.
PubMed: 29399429
DOI: 10.4172/2168-9296.1000190 -
Biochimica Et Biophysica Acta.... Dec 2017Fish oil is a rich source of omega-3 fatty acids which disrupt lipid microdomain structure and affect mobility of the prostaglandin F (FP) receptor in bovine luteal...
Fish oil is a rich source of omega-3 fatty acids which disrupt lipid microdomain structure and affect mobility of the prostaglandin F (FP) receptor in bovine luteal cells. The objectives of this study were to determine the effects of individual omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on 1) membrane fatty acid composition, 2) lipid microdomain structure, and 3) lateral mobility of the FP receptor in bovine luteal cells. Ovaries were collected from a local abattoir (n=5/experiment). The corpus luteum was resected and enzymatically digested using collagenase to generate a mixed luteal cell population. In all experiments, luteal cells were treated with 0, 1, 10 or 100μM EPA or DHA for 72h to allow incorporation of fatty acids into membrane lipids. Results from experiment 1 show that culturing luteal cells in the presence of EPA or DHA increased these luteal fatty acids. In experiment 2, both EPA and DHA increased spatial distribution of lipid microdomains in a dose-dependent manner. Single particle tracking results from experiment 3 show that increasing both EPA and DHA concentrations increased micro- and macro-diffusion coefficients, increased domain size, and decreased residence time of FP receptors. Collectively, results from this study demonstrate similar effects of EPA and DHA on lipid microdomain structure and lateral mobility of FP receptors in cultured bovine luteal cells. Moreover, only 10μM of either fatty acid was needed to mimic the effects of fish oil.
Topics: Animals; Cattle; Docosahexaenoic Acids; Dose-Response Relationship, Drug; Eicosapentaenoic Acid; Female; Luteal Cells; Membrane Lipids; Membrane Microdomains; Primary Cell Culture; Protein Transport; Receptors, Prostaglandin
PubMed: 28912100
DOI: 10.1016/j.bbamem.2017.09.012 -
Journal of Ovarian Research Jul 2014Luteal activity is dependent on the interaction of various growth factors, cytokines and hormones, including the thyroid hormones, being that hypo- and hyperthyroidism...
BACKGROUND
Luteal activity is dependent on the interaction of various growth factors, cytokines and hormones, including the thyroid hormones, being that hypo- and hyperthyroidism alter the gestational period and are also a cause of miscarriage and stillbirth. Because of that, we evaluated the proliferation, apoptosis and expression of angiogenic factors and COX-2 in the corpus luteum of hypo- and hyperthyroid pregnant rats.
METHODS
Seventy-two adult female rats were equally distributed into three groups: hypothyroid, hyperthyroid and control. Hypo- and hyperthyroidism were induced by the daily administration of propylthiouracil and L-thyroxine, respectively. The administration began five days before becoming pregnant and the animals were sacrificed at days 10, 14, and 19 of gestation. We performed an immunohistochemical analysis to evaluate the expression of CDC-47, VEGF, Flk-1 (VEGF receptor) and COX-2. Apoptosis was evaluated by the TUNEL assay. We assessed the gene expression of VEGF, Flk-1, caspase 3, COX-2 and PGF2α receptor using real time RT-PCR. The data were analyzed by SNK test.
RESULTS
Hypothyroidism reduced COX-2 expression on day 10 and 19 (P < 0.05), endothelial/pericyte and luteal cell proliferation on day 10 and 14 (p < 0.05), apoptotic cell numbers on day 19 (p < 0.05) and the expression of Flk-1 and VEGF on day 14 and 19, respectively (p < 0.05). Hyperthyroidism increased the expression of COX-2 on day 19 (P < 0.05) and the proliferative activity of endothelial/pericytes cells on day 14 (p <0.05), as well as the expression of VEGF and Flk-1 on day 19 (P < 0.05).
CONCLUSIONS
Hypothyroidism reduces the proliferation, apoptosis and expression of angiogenic factors and COX-2in the corpus luteum of pregnant rats, contrary to what is observed in hyperthyroid animals, being this effect dependent of the gestational period.
Topics: Animals; Caspase 3; Corpus Luteum; Cyclooxygenase 2; Disease Models, Animal; Female; Gene Expression; Hormones; Hyperthyroidism; Hypothyroidism; Immunohistochemistry; Male; Minichromosome Maintenance Complex Component 7; Pregnancy; Rats; Receptors, Prostaglandin; Transcription, Genetic; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2
PubMed: 25298361
DOI: 10.1186/1757-2215-7-75 -
Frontiers in Endocrinology 2019The luteinization of the follicular cells, following a LH surge, causes extensive molecular and structural changes in preovulatory follicles (POF) that lead to ovulation...
The luteinization of the follicular cells, following a LH surge, causes extensive molecular and structural changes in preovulatory follicles (POF) that lead to ovulation and ultimate formation of the corpus luteum (CL). The objective of this study was to identify proteins expressed in porcine POF before the LH surge and a new CL formed, 2-3 days after ovulation, and evaluate proteome changes associated with formation of the CL from a follicle. We used 2D-gel electrophoresis-based proteomics and tandem mass spectrometry followed by a functional analysis using Ingenuity Pathway analysis (IPA) to evaluate functional pathways associated with the luteinization process. Protein lysates were prepared from isolated POFs and from the newly formed CL. A total of 422 protein spots were identified in both structures. A total of 15 and 48 proteins or their proteoforms were detected only in the POFs and CL, respectively. An IPA analysis of a POF proteome showed that most of the follicular proteins were involved in cellular infiltration, endoplasmic stress responses, and the protein ubiquitination pathway. Most of the early luteal proteins were associated with steroid metabolism, cell death and survival, free radical scavenging, and the protein ubiquitination pathway. A comparison of a follicular proteome with that of an early luteal proteome revealed that 167 identified proteins or their proteoforms were differentially regulated between POFs and the newly formed CL ( < 0.05 and a fold change of >1.8). Proteins that were significantly more abundant in follicles included cAMP-dependent protein kinase, histone binding protein RBBP4, reticulocalbin, vimentin, and calumenin; more abundant luteal proteins included albumin, farnesyl diphosphate synthase, serine protease inhibitors, elongation factor-1, glutaredoxin, and selenium-binding protein. Proteins that were significantly altered with luteal formation were found to be associated with cholesterol biosynthesis, cell death and survival, and acute phase response. Moreover, upstream regulators of differentially abundant proteins in CL were identified that included insulin growth factor-1, sterol regulatory element-binding transcription factor-1, and nuclear factor erythroid-derived 2. We have identified novel proteins that advance our understanding of (1) processes associated with differentiation of POFs into the CL, (2) possible mechanisms of luteal cell survival, and (3) pathways regulating steroidogenesis in the newly formed CL.
PubMed: 31798533
DOI: 10.3389/fendo.2019.00774