The corpus luteum (CL) is one of the few endocrine glands that forms from the remains of another organ and whose function and survival are limited in scope and time. The CL is the site of rapid remodeling, growth, differentiation, and death of cells originating from granulosa, theca, capillaries, and fibroblasts. The apparent raison d'etre of the CL is the production of progesterone, and all the structural and functional features of this gland are geared toward this end. Because of its unique importance for successful pregnancies, the mammals have evolved a complex series of checks and balances that maintains progesterone at appropriate levels throughout gestation. The formation, maintenance, regression, and steroidogenesis of the CL are among the most significant and closely regulated events in mammalian reproduction. During pregnancy, the fate of the CL depends on the interplay of ovarian, pituitary, and placental regulators. At the end of its life span, the CL undergoes a process of regression leading to its disappearance from the ovary and allowing the initiation of a new cycle. The generation of transgenic, knockout and knockin mice and the development of innovative technologies have revealed a novel role of several molecules in the reprogramming of granulosa cells into luteal cells and in the hormonal and molecular control of the function and demise of the CL. The current review highlights our knowledge on these key molecular events in rodents.

The Molecular Control of Corpus Luteum Formation, Function, and Regression

The roles of cellular reactive oxygen species, oxidative stress and antioxidants in pregnancy outcomes

The ovary and uterus undergo extensive tissue remodeling throughout each reproductive cycle. This remodeling of the extracellular environment is dependent upon the cyclic hormonal changes associated with each estrous or menstrual cycle. In the ovary, tissue remodeling is requisite for growth and expansion of the follicle, breakdown of the follicular wall during the ovulatory process, transformation of the postovulatory follicle into the corpus luteum, as well as the structural dissolution of the corpus luteum during luteal regression. In the uterus, there is extraordinary turnover of the endometrial connective tissue matrix during each menstrual cycle. This turnover encompasses the complete breakdown and loss of this layer, followed by its subsequent regrowth. With implantation, extensive remodeling of the uterus occurs to support placentation. These dynamic changes in the ovarian and uterine extracellular architecture are regulated, in part, by the matrix metalloproteinase (MMP) system. The MMP system acts to control connective tissue remodeling processes throughout the body and is comprised of both a proteolytic component, the MMPs, and a regulatory component, the associated tissue inhibitors of metalloproteinases. The current review will highlight the key features of the MMPs and tissue inhibitors of metalloproteinases, focus on the changes and regulation of the MMP system that take place throughout the estrous and menstrual cycles, and address the impact of the dynamic tissue remodeling processes on ovarian and uterine physiology.

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The Matrix Metalloproteinase System: Changes, Regulation, and Impact throughout the Ovarian and Uterine Reproductive Cycle

Contrary to the prevalent view, there seems to be no competition in the mammalian female genital tract among large numbers of sperm cells that are racing towards the egg. Instead, small numbers of the ejaculated sperm cells enter the Fallopian tube, and these few must be guided to make the remaining long, obstructed way to the egg. Here, we review the mechanisms by which mammalian sperm cells are guided to the egg.

https://www.royanaward.com/files13/Royan%20Award%20-%20Giojalas%20-%20pdf%20paper%201.pdf

Sperm guidance in mammals - an unpaved road to the egg.

The effect of ascorbic acid supplementation on sperm quality, lipid peroxidation and testosterone levels of male Wistar rats.

Ascorbic acid has long been associated with fertility, but no consistent study of its mechanism of action in reproductive tissues has been made. This article considers how three of ascorbic acid's principal functions, namely its promotion of collagen synthesis, its role in hormone production, and its ability to protect cells from free radicals, may explain its reproductive actions. Data relating to both ovary and testis are reviewed since ascorbate accumulates in both tissues. Both gonads exhibit cycles of tissue remodeling and of peptide and steroid secretion that can be assumed to be ascorbate-dependent. Ascorbic acid may also prevent gametes from damage by free radicals during production and fertilization. Preliminary data on the concentrations of ascorbic acid in serum and follicular fluid from women undergoing in vitro fertilization are presented. They suggest that the supply of ascorbic acid to the ovary might be a limiting factor in the ability of the preovulatory follicle to grow in response to gonadotropin stimulation. It is concluded that ascorbic acid is a key compound in gonadal physiology on which further research is needed and that a reappraisal of its potential clinical value in the treatment of various types of male and female infertility would be timely.

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Ascorbic acid and fertility.

A preliminary quantitative and qualitative analysis of the collagen component of the bovine luteal extracellular matrix is reported. The amount of collagen present in corpora lutea from four stages of luteal development was estimated from measurements of hydroxyproline. The tissue content of ascorbic acid, a cofactor in collagen biosynthesis, was also determined. Extracts of luteal tissue were subjected to polyacrylamide gel electrophoresis and compared with patterns derived from standard preparations of commonly occurring collagens. Measurements of hydroxyproline showed that collagen contributed up to about one-sixth of the luteal dry matter (3% of wet weight), with the highest absolute amounts occurring in mature tissue. Ascorbic acid was present in tissue from all stages of the luteal phase, with the highest concentrations occurring in the midluteal phase. Hydroxyproline content was closely correlated with tissue weight and ascorbic acid content during the first stage of the luteal phase, indicating that collagen is produced as a component of tissue growth, supported by the concurrent accumulation of its biosynthetic cofactor. The highest concentrations of hydroxyproline occurred in the final stage of the luteal phase, suggesting that luteolysis is associated with a preferential loss of cellular rather than extracellular material. From the electrophoretic analysis, the fibrillar collagen type I could be identified at all stages of the luteal phase. We conclude that collagen is a major component of the luteal extracellular matrix and is produced as an integral component of tissue development. The presence of a fibrillar rather than a basement membrane type of collagen suggests a significant change in gene expression when follicular tissue is remodelled into that of the corpus luteum.

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Identification and measurement of collagen in the bovine corpus luteum and its relationship with ascorbic acid and tissue development

The aim of this study was to locate sites of expression and deposition of collagen, fibronectin and laminin in the bovine ovary. RNA from the granulosa and basement membrane/theca fractions of maturing follicles and from corpora lutea of the early, middle and late luteal phase was probed with cDNAs for collagen types I and IV, fibronectin and laminin. Antisera against collagens I and IV were used in western analysis of protein from follicular fluid, granulosa, basement membrane/theca and corpus luteum. Collagen subunits alpha 1(I) and alpha 2(I) were expressed in the basement membrane/theca but not in the granulosa of the follicle. They were also expressed in all luteal extracts, especially those from the early phase. Collagen alpha 2(IV) was highly expressed in the basement membrane/theca and to a lesser extent in corpora lutea. Collagen alpha 3(IV) was expressed in the granulosa, basement membrane/theca and early corpus luteum. Fibronectin 1 and laminin B2 were expressed in all tissues. Laminin B1 was expressed in all tissues except the granulosa. Collagen IV was immunodetected in all follicle extracts, with the strongest signal in the basement membrane/theca. Collagen I occurred in all luteal extracts and in the basement membrane/theca but not in follicular fluid or the granulosa. These results demonstrate tissue-specific expression of ovarian structural proteins and suggest that changes occur during the progression from follicle to corpus luteum. The production of collagen IV in the follicle wall and of collagen I in the corpus luteum is consistent with previous biochemical studies. Evidence for collagen IV in the follicular antrum suggests that the follicle wall originates from granulosa as well as theca cells.(ABSTRACT TRUNCATED AT 250 WORDS)

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Gene expression and protein distribution of collagen fibronectin and laminin in bovine follicles and corpora lutea

During follicular development the proliferative and differentiated state of the epithelioid granulosa cells changes, and the movement of fluid across the follicular basal lamina enables the formation of an antrum. Type IV collagen is an important component of many basal laminae. Each molecule is composed of three alpha chains; however, six different type IV collagen chains have been identified. It is not known which of these chains are present in the follicular basal lamina and whether the type IV collagen composition of the basal lamina changes during follicular development. Therefore, we immunolocalized each of the six chains in bovine ovaries using antibodies directed to the nonconserved non-collagenous (NC) domains. Additionally, dissected follicles were digested with collagenase to release the NC domains, and the NC1 domains were then detected by standard Western immunoblot methods. The follicular basal lamina of almost all primordial and preantral follicles was positive for all type IV collagen alpha chains. Colocalization of type IV collagen and factor VIII-related antigen allowed for discrimination between the follicular and endothelial basal laminae. Type IV collagen alpha1, alpha2, alpha3, alpha4, and alpha5 chains were present within the follicular basal lamina of only a proportion of antral follicles (17 of 22, 20 of 21, 15 of 18, 14 of 28, and 12 of 23, respectively), and staining was less intense than in the preantral follicles. Staining for the alpha1 and alpha2 chains was diffusely distributed throughout the theca in regions not associated with recognized basal laminae. The specificity of this immunostaining for alpha1 and alpha2 chains of type IV collagen was confirmed by Western immunoblots. As well as being detected in the basal lamina of approximately half of the antral follicles examined, type IV collagen alpha4 also colocalized with 3beta-hydroxysteroid dehydrogenase-immunopositive cells in the theca interna. Type IV collagen alpha6 was detected in the basal lamina of only one of the 16 antral follicles examined. Thus, the follicular basal lamina changes in composition during follicular development, with immunostaining levels being reduced for all type IV collagen chains and immunoreactivity for type IV collagen alpha6 being lost as follicle size increases. Additionally, immunoreactivity for alpha1 and alpha2 appears in the extracellular matrix of the theca as it develops.

Distribution of the α1 to α6 Chains of Type IV Collagen in Bovine Follicles

The effects of FSH, LH, and epidermal growth factor (EGF) on the dynamics of nuclear maturation and subsequent embryo development were examined in pig oocytes cultured either conventionally or after preincubation with cycloheximide (CHX). In conventional culture, FSH or EGF significantly increased the rate of attainment of metaphase II (MII) for both gilt (50.0% ± 4.2% and 54.8% ± 4.3%, respectively; control, 5.8% ± 1.8%; P 80%), fewer FSH-treated oocytes reached metaphase I (43.8% ± 5.3%, P < 0.001) by 14 h and MII (48.4% ± 5.9%, P < 0.001) by 24 h, although the majority (71%) did mature to MII by 36 h af...

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Dynamic Changes in Meiotic Progression and Improvement of Developmental Competence of Pig Oocytes in Vitro by Follicle-Stimulating Hormone and Cycloheximide

M R Luck

Papers

Ascorbic acid and fertility.

Identification and measurement of collagen in the bovine corpus luteum and its relationship with ascorbic acid and tissue development

Gene expression and protein distribution of collagen fibronectin and laminin in bovine follicles and corpora lutea

Distribution of the α1 to α6 Chains of Type IV Collagen in Bovine Follicles

Dynamic Changes in Meiotic Progression and Improvement of Developmental Competence of Pig Oocytes in Vitro by Follicle-Stimulating Hormone and Cycloheximide