Granulosa cell

Follicular fluid and granulosa cells derived at ovum pickup in an IVF treatment, can reflect the qualities of the follicle, and therefore the oocyte. 

In vitro, granulosa cells can be cultured and secrete hormones. Estradiol and progesterone secreted in vitro by granulosa cells are not correlated with treatment outcome, but relaxin secretion is correlated with conception and with term pregnancy (S25). Relaxin has a stimulating effect on endometrium, and this might be the reason for the reported correlation. 

Apoptosis was measured by TdT-mediated dUTP nick end labeling (TUNEL) by flow cytometry as described by Gorczyca et al. (G6). Every measurement was done in duplo, and a negative and postive control were carried out with each experiment. All patients had normal basal FSH levels, and their partners had normal semen 

It can be concluded that in IVF, women who have more apoptosis in their follicles, reflected by percentage apoptotic granulosa cells, also have less chance of pregnancy. 

Choosing the right embryo(s) for embryo transfer is essential in optimizing pregnancy rates in IVF. If transfer of only one embryo in order to prevent multiple 

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In premenopausal women the ovary is the richest source of aromatase and hence estrogen. Aromatase is confined to the granulosa cells and is produced under the influence of gonadotropins (FSH and LH). Despite being a rich source of aromatase, three separate studies have shown that aromatase inhibitors are unable to sufficiently suppress ovarian estrogen production to postmenopausal levels. One explanation for this phenomenon may be a compensatory rise in gonadotrophins which maintains adequate estrogen production, despite the presence of the inhibitor. As such aromatase inhibitors cannot be used in premenopausal breast cancer patients. After menopause, ovarian... 

The ceUular source of the various ovarian steroids has been difficult to unravel, but a transfer of substrates between two cell types is involved. Theca cells are the source of androstenedione and testosterone. These are converted by the aromatase enzyme in granulosa cells to estrone and estradiol, respectively. Progesterone, a precursor for all steroid hormones, is produced and secreted by the corpus luteum as an end-product hormone because these cells do not contain the enzymes necessary to convert progesterone ro other steroid hormones (Figure 42-8). 

The follicular granulosa cells are the major site of synthesis of female steroid sex hormones the oestrogens. P-Oestradiol represents the principal female follicular oestrogen. Oestriol is produced by the placenta of pregnant females. Oestriol and oestrone are also produced in small quantities as products of P-oestradiol metabolism. 

Long GG, Cohen IR, Gries CL, Young JK, Francis PC, Capen CC (2001) Proliferative lesions of ovarian granulosa cells and reversible hormonal changes induced in rats by a selective estrogen receptor modulator. Toxicol Pathol 29 719-726... 

The follicular phase covers the development of the follicle, which involves an increase in its size due to an increase in follicular fluid, growth of the ovum (i.e. an increase in the contents of RNA and protein) and an increase in the number of cells that surround the ovum. These cells are of two types, the granulosa and the thecal cells. The role of these cells is to synthesise and secrete the steroid hormones oestrogens (mainly oestradiol). The precursor molecule for their synthesis is cholesterol. There is a division of labour between these cells the thecal cells convert cholesterol into the male sex hormones androstenedione and testosterone, which are released into the blood to be taken up by the granulosa cells where they are converted to the oestrogens (Figure 19.8). For details of pathways, see Appendix 19.1. 

Figure 19.8 A brief summary of the pathways for formation and secretion of oestradiol and progesterone within the cells of the follicle. Cholesterol is taken up by thecal cells in a complex with low density lipoprotein. In the thecal cells, cholesterol is converted to testosterone which is released to be taken up by granulosa cells where it is converted into oestradiol. For synthesis of progesterone in the granulosa cells, cholesterol is synthesised de novo within the cells from acetyl-CoA. In the follicle the enzyme aromatase, which produces the aromab c ring in the female sex hormones, is restricted to the granulosa cells. The reacrions that are stimulated by LH and FSH increase synthesis and, therefore, secretion of testosterone and increased synthesis of oestrogens and progesterone.

A long-held view is that oestrogens are the hormones that control reproductive activity in the female and that androgens control the activity in the male. Although this is broadly the case, such a complete separation is too simple. For example, testosterone is secreted by the thecal cells in the ovary and although some is taken up by the granulosa cells for conversion to an oestrogen, some remains in the blood, where it has several roles (e.g. stimu-... 

Stimulation of ovarian granulosa cells with follicle-stimulating hormone results in the phosphorylation of H3 at Ser-10 [74]. However, neither the Ras-Raf-MEK-ERK signal transduction nor the p38 stress kinase pathways are involved in this response. 

Follicle-stimulating hormone (FSH) induces the Ser-10 phosphorylation of H3 in ovarian granulosa cells by activation of protein kinase A. Based on the response to various protein kinase inhibitors, FSH-stimulated phosphorylation did not involve Rsk2 or MSKl [74]. 

Chronic oral exposure of rats and mice to MDA and its dihydrochloride is carcinogenic. Treatment-related increases in the incidences of thyroid follicular cell adenomas and hepatocellular neoplasms were observed in mice after chronic ingestion of MDA in drinking water. In rats, increases in the incidences of thyroid follicular cell carcinoma and hepatic nodules were observed in males and thyroid follicular cell ademonas occurred in females. Although not statistically significant, certain uncommon tumors such as bile duct adenomas, papillomas of the urinary bladder, and granulosa cell tumors of the ovary also were reported. These tumors are of low incidence in historical controls. In another report, MDA acted as a promoter of thyroid tumors in rats. °... 

K6. Khan, S. M., Dauffenbach, L. M., and Yeh, J., Mitochondria and caspases in induced apoptosis in human luteinized granulosa cells. Biochem. Biophys. Res. Commun. 269, 542-545 (2000). 

In the human female, IGF-1 is expressed by follicular theca cells, while IGF-2 is synthesized by granulosa cells (Chapter 8). The IGF-1 and -2 receptors are widely expressed in ovarian tissue, and synthesis of both growth factors and their receptors are influenced by circulating gonadotrophin levels. IGF-1 exerts a direct mitogenic effect on human granulosa cells, and promotes increased androgen and oestradiol synthesis by these cells. IGF-1 also promotes increased expression of FSH and LH receptors in ovarian tissue. 

During the follicular phase of the menstrual cycle, one or more follicles are prepared for ovulation. FSH and estrogens are the most important hormones for this developmental process. Complete follicular maturation cannot occur in the absence of LH. Rupture of a mature follicle follows the midcycle peak of LH and FSH by about 24 hours. In humans, usually one mature ovum is released per cycle. During the luteal phase of the menstrual cycle and under the influence of LH, the ovarian granulosa cells of the corpus luteum become vacuolated and accumulate a yellow pigment called lutein. 

The maternal ovaries are removed and examined at the time of necropsy and corpora lutea are counted. The corpus luteum (CL) is a transitory endocrine organ formed from the thecal and granulosa cells of the postovulatory follicle... Information on the number of copora lutea is useful in the interpretation of data on the viability of conceptuses (see below, pre-implantation loss). Corpora lutea counts can be conducted with fresh or fixed tissue, and are generally performed with the aid of a dissecting microscope. Minimal dissection of the ovarian tissue is required (13). 

Anti-convulsant activity. Methanol (50%) extract of the dried leaf, administered to mice, was active vs leptazol-induced convulsions . Ethanol (70%) extract of the fresh leaf, administered intraperito-neally to mice of both sexes at variable doses, was active vs metrazole- and strychnine-induced convulsions . Anti-estrogenic effect. Aqueous extract of the dried leaf smoke, administered to female adults at a concentration of 25.0 pL/plate, was active on granulosa cells. Results significant atp < 0.001 level . 

Following the above events, the cavity of the ruptured follicle fills with blood (corpus hemorrhagicum), and the luteinized theca and granulosa cells proliferate and replace the blood to form the corpus luteum. The cells of this structure produce estrogens and progesterone for the remainder of the cycle, or longer if pregnancy occurs. 

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