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PubMed2006

Association of decreased mitochondrial DNA content with ovarian cancer progression.

Mitochondrial DNA (mtDNA) content in ovarian carcinomas was assessed by quantitative PCR. Results show that mtDNA content in tumour cell was significantly higher than that in normal ovary. Change in mtDNA content was not related with patients' age or tumour stages. However, the average mtDNA copy number in pathological low-grade tumours was over two-fold higher than that in high-grade carcinomas (P=0.012). Moreover, type I carcinomas also had a significantly higher mtDNA copy number than in type II carcinomas (P=0.019). Change in mtDNA content might be an important genetic event in the progression of ovarian carcinomas.

Adenocarcinoma, Clear Cell↗

PubMed1993

Blood flow velocity in the uterine and ovarian arteries during the normal menstrual cycle.

Twelve healthy women with regular menstrual cycles were examined with a combination of two-dimensional real-time ultrasound and color and spectral Doppler techniques on cycle days 4 and 8 and daily from cycle day 12 until follicular rupture, then days + 1, +2, +5, +7 and +12 after follicular rupture. The uterine and subendometrial arteries, arteries in the ovarian stroma and hilum, in the wall of the largest follicle of each ovary, and in the wall of the corpus luteum were examined. The pulsatility index and the time-averaged maximum velocity were calculated. In the uterine arteries the pulsatility index was highest on day + 2, after which it decreased successively to its lowest value, whereas the time-averaged maximum velocity reached its highest value on day + 12. Similar changes were observed in the subendometrial arteries. In the non-dominant ovary, neither the pulsatility index nor the time-averaged maximum velocity manifested any consistent changes during the cycle. In the dominant ovary, the time-averaged maximum velocity increased and the pulsatility index decreased after follicular rupture, being significantly higher and lower, respectively, in the luteal than in the follicular phase. These changes were seen in the ovarian hilum, stroma and follicular wall, but were most obvious in the wall of the dominant follicle and of the corpus luteum. We conclude that the blood circulation in the uterus and in the dominant ovary changes considerably during the menstrual cycle, whereas that in the non-dominant ovary shows no unequivocal changes.

Journal Article↗

PubMed2003

Cloning, expression, and characterization of a membrane progestin receptor and evidence it is an intermediary in meiotic maturation of fish oocytes.

The structures of membrane receptors mediating rapid, nongenomic actions of steroids have not been identified. We describe the cloning of a cDNA from spotted seatrout ovaries encoding a protein that satisfies the following seven criteria for its designation as a steroid membrane receptor: plausible structure, tissue specificity, cellular distribution, steroid binding, signal transduction, hormonal regulation, and biological relevance. For plausible structure, computer modeling predicts that the protein has seven transmembrane domains, typical of G protein-coupled receptors. The mRNA (4.0 kb) is only detected in the brain and reproductive tissues on Northern blots. Antisera only detect the protein (40 kDa) in plasma membranes of reproductive tissues. The recombinant protein produced in an Escherichia coli expression system has a high affinity (K(d) = 30 nM), saturable, displaceable, single binding site specific for progestins. Progestins alter signal transduction pathways, activating mitogen-activated protein kinase and inhibiting adenylyl cyclase, in a transfected mammalian cell line. Inhibition of adenylyl cyclase is pertussis toxin sensitive, suggesting the receptor may be coupled to an inhibitory G protein. Progestins and gonadotropin up-regulate both mRNA and protein levels in seatrout ovaries. Changes in receptor abundance in response to hormones and at various stages of oocyte development, its probable coupling to an inhibitory G protein and inhibition of progestin induction of oocyte maturation upon microinjection of antisense oligonucleotides are consistent with the identity of the receptor as an intermediary in oocyte maturation. These characteristics suggest the fish protein is a membrane progestin receptor mediating a "nonclassical" action of progestins to induce oocyte maturation in fish.

Animals↗

PubMed2000

Localization of the progesterone receptor in the porcine ovary.

Regulation of progesterone receptor (PR) expression has been studied in many species. However, precise studies have not yet been performed in the porcine ovary. We have examined the localization of PR in follicles and corpora lutea of the porcine ovary at different stages of their development. The effects of LH and FSH on PR expression in granulosa cells of small antral follicles was also studied. Immunohistochemistry was applied to determine the distribution of PR while immunoblot analysis showed that two isoforms A and B were present. Early antral follicles contained PR in the granulosa layer. In granulosa cells of small and medium antral follicles PR was not detected whereas it was present in the theca layer. Before ovulation, PR was found in both granulosa and theca cells of large follicles and the staining intensity was very strong. FSH or LH treatment of small follicles (100 ng/ml) induced changes in cellular distribution patterns of PR. In both cases, PR was expressed in granulosa cells. PR was detected in corpora lutea in all 3 stages of the luteal phase. Our data show that in the pig ovary changes in PR localization are stage-specific and suggest that expression of PR is positively regulated by both LH and FSH.

Animals↗

PubMed2001

Estrogen receptor beta in the sheep ovary during the estrous cycle and early pregnancy.

Objectives were to sequence and examine the expression of the estrogen receptor beta (ERbeta) in the sheep ovary. The sequence of the ovine ERbeta (oERbeta) was determined using reverse-transcription polymerase chain reaction (RT-PCR) and cloning techniques. The reading frame of oERbeta contained 527 amino acids and exhibited high overall homology with cow (98%), rat (88%), and human (88%) ERbeta. In addition, an oERbeta isoform having a 139-base pair deletion (oERbeta1) was identified. The predicted amino acid sequence of this isoform is lacking the ligand-binding and carboxyl-terminal transactivation domains. The oERbeta protein and mRNA were determined in ovaries obtained from ewes on Days 0 (first day of estrus), 2, 6, and 10 of the estrous cycle and Day 30 of gestation. Immunohistochemistry showed that oERbeta protein was located in granulosa cells, the ovarian surface epithelium, endothelium, and Day 2 corpus luteum (CL). Weak immunostaining for ERbeta was detected in the theca interna. Relative steady-state amounts of oERbeta mRNA in the CL were determined using semiquantitative RT-PCR. Amounts of oERbeta mRNA were greater (P < 0.05) during CL formation (Day 2) than at later stages. The oERbeta to oERbeta1 mRNA ratio was lower (P < 0.05) on Day 2 than on Day 10 or Day 30 due to a decrease in amounts of oERbeta1. Results indicate that the oERbeta is a 527-amino acid protein expressed in specific cells of the ovary. Changes in relative amounts of full-length oERB and a deletion isoform in CL occurred during the estrous cycle, suggesting that these two types of ERbeta might regulate estrogen actions during early CL development in sheep.

Amino Acid Sequence↗

PubMed1990

Changes in the Level of Peptidase Activities in Pea Ovaries during Senescence and Fruit Set Induced by Gibberellic Acid.

The activities and changes in the levels of exopeptidase and endopeptidase activities were characterized in unpollinated ovaries of Pisum sativum L. cv Alaska during senescence and early fruit development induced by gibberellic acid (GA(3)). Two aminopeptidases and one iminopeptidase were electrophoretically separated. These peptidases were sensitive to inhibitors of sulfhydryl proteases. Carboxypeptidase activity was inhibited by phenylmethyl sulfonyl fluoride. An azocasein-degrading endopeptidase, sensitive to thiol protease inhibitors, was also found. An increase in the specific activity of aminopeptidase during both fruit development and ovary senescence was observed. In contrast, the specific activity of carboxypeptidase and endopeptidase increased only during senescence of the ovary. Changes in exopeptidase activity in senescing ovaries could be mainly the consequence of a greater stability to proteolysis while the rise in endopeptidase activity appeared to be due to new or increased synthesis of the enzyme. These results suggest that endopeptidase, and not amino or carboxypeptidase, plays a key role in the senescence of pea ovaries and that the changes in unpollinated ovaries leading to ovary senescence or fruit development can be controlled by gibberellins.

Journal Article↗

PubMed1993

Human ovarian aging and mitochondrial DNA deletion.

The functions of human ovary change dynamically around the menopausal period. A decrease of the number of primordial follicles and an increase of fibrous tissues are observed histologically in the aged ovary. As endocrinological aspects at menopause, the synthesis and secretion of ovarian steroid hormones such as estrogens and progesterone decrease, followed with the resultant increases of pituitary gonadotropins. However, the mechanism of menopause and ovarian aging is not well understood. Thus, to study the regulatory mechanism of ovarian dysfunction by aging, we analyzed the accumulation of mitochondrial DNA (mtDNA) mutation in the human ovary in women of various ages. The amplification of a 5.5-kb region in mtDNA with polymerase chain reaction revealed a 0.5-kb band in ovarian samples obtained from menopausal and postmenopausal women, which means that the 5.0-kb deletion of mtDNA in ovarian tissue starts at the menopausal period. The close relationship between the occurrence of ovarian mtDNA deletion and the menstrual irregularity was also observed. These observations suggest that the accumulation of the deleted mtDNA may be a regulating factor of dysfunction of the ovary by aging.

Adult↗

PubMed1994

Growth hormone stimulates follicular development by stimulating ovarian production of insulin-like growth factor-I.

The present study was undertaken to investigate the effects of GH on follicular growth, oocyte maturation, ovulation, and production of insulin-like growth factor-I (IGF-I) in the in vitro perfused rabbit ovaries. Ovulation did not occur in any ovaries perfused with GH at a concentration of 1, 10, 100, or 200 ng/ml, but the addition of GH to the perfusate increased the follicle diameter in a dose-dependent manner. The production of IGF-I by ovaries perfused with medium alone was very low throughout the perfusion period. The addition of 100 ng/ml GH to the perfusate significantly increased ovarian production of IGF-I at 4, 6, 8, and 12 h compared with the contralateral control ovaries. Changes in the tissue concentrations of IGF-I in ovaries perfused with 100 ng/ml GH paralleled those triggered by exposure to 50 IU human CG (hCG). When the effect of GH on the tissue concentration of IGF-I was determined at 4 h, GH stimulated the tissue concentration of IGF-I in perfused rabbit ovaries in a dose-dependent manner. The percent increase in follicle diameter in ovaries treated with GH was significantly correlated with the intraovarian IGF-I content. The mean number of ovulations per ovary and the ovulatory efficiency were significantly reduced in ovaries perfused with 5 IU hCG, compared with those in ovaries perfused with 50 IU hCG. The addition of 100 ng/ml GH to the perfusate significantly increased the ovulatory efficiency and follicle diameter in the 5 IU hCG-treated ovaries. Exposure to GH significantly stimulated the resumption of meiosis in the follicular oocytes compared with that in ovaries perfused with medium alone. Furthermore, GH significantly stimulated the resumption of meiosis in ovulated ova and follicular oocytes in ovaries treated with 5 IU hCG. Thus, exposure to GH-stimulated follicular growth, oocyte maturation, and production of IGF-I in the in vitro perfused rabbit ovaries, which indicates that the ovary is in fact a site of GH reception and action. Additionally, GH enhanced the effects of gonadotropins, acting synergistically to promote the ovulatory process. These observations suggest that GH may amplify gonadotropin actions in the process of follicular development and ovulation, at least in part, by stimulating ovarian IGF-I production.

Animals↗

PubMed2002

Relationship among insulin-like growth factor-I, blood metabolites and postpartum ovarian function in dairy cows.

The relationship among nutritional status, systemic insulin-like growth factor-I (IGF-I) and ovarian function early postpartum were investigated. A total of 27 Holstein-Friesian cows, 10 that cycled normally within 20 days postpartum, 5 diagnosed with follicular cysts, 8 with persistent corpus luteum (CL) after the first ovulation postpartum and 4 with inactive ovaries were used for the study. Blood samples were collected 1-3 times per week, for 60 days pre- and postpartum, for IGF-I, progesterone, estradiol, free fatty acids (FFA), blood urea nitrogen (BUN), and aspartate aminotransferase (AST) determination. Inactive ovary and cystic cows had a higher body condition score before calving and lost more condition than normal or persistent CL cows. Immediately postpartum, IGF-I levels were higher and rose sharply in cows that cycled normally than in cystic, inactive ovary or persistent CL cows. At calving and early postpartum, FFA was higher in inactive ovary and cystic than in normal and persistent CL cows. There was a significant strong positive relationship between IGF-I and BUN, and strong negative relationships between IGF-I and FFA and AST in all groups. There was a positive relationship between serum IGF-I and estradiol in normal cystic and inactive ovary cows. This study found that overconditioned cows during the dry period or at calving, lost more body condition postpartum. These cows also had a deeper and longer period of negative energy balance (NEB), poor liver function and low circulating IGF-I concentrations early postpartum. Such cows were likely to have poor reproductive function as seen in development of cystic ovaries, persistent CL and inactive ovary. Changes in serum IGF-I early postpartum may help predict both nutritional and reproductive status in dairy cattle.

Animals↗

PubMed2003

Interactions between nutrition and ovarian activity in cattle: physiological, cellular and molecular mechanisms.

The effects of acute changes in dietary intake on ovarian activity can be correlated with changes in circulating concentrations of metabolic hormones including insulin, insulin-like growth factor I (IGF-I), growth hormone and leptin. There is no corresponding change in circulating gonadotrophin concentrations and it is proposed that the dietary induced changes in ovarian activity, resulting from acute changes in dietary intake, are a result of direct actions of these metabolic hormones on the ovary. Changes in the peripheral concentrations of insulin, IGF-I and leptin were also associated with the initiation of a synchronized wave of follicle growth and it is hypothesized that oestrogen secreted by the developing follicle is involved in regulating the secretion of these metabolic hormones. At the cellular level, physiological concentrations of insulin and IGF-I interact to stimulate oestradiol production by granulosa cells. In contrast, leptin inhibits FSH-stimulated oestradiol production by granulosa cells and LH-stimulated androstenedione production by theca cells. At the molecular level, dietary energy intake affects the expression of mRNA encoding components of the ovarian IGF system and these changes can directly influence the bioavailability of intrafollicular IGF. This, in turn, can increase the sensitivity or response of follicles to FSH and is one mechanism through which nutrition can directly affect follicle recruitment. Dietary induced increases in intrafollicular IGF bioavailability also have a negative effect on oocyte quality, and diets that are optimal for follicle growth may not necessarily be optimal for oocyte maturation.

Animal Nutritional Physiological Phenomena↗

PubMed2003

Alterations in polypeptides pattern in malaria vector Anopheles stephensi, fed upon immunized blood causing fecundity reduction.

Changes in polypeptides pattern of haemolymph, midgut, ovary and salivary glands of female mosquito A. stephensi were studied when fed upon anti-mosquito haemolymph antibodies. The expression of almost all polypeptides was reduced in haemolymph and ovary of the immune fed mosquitoes as compared to control. However, there was no significant difference in case of midgut and salivary glands. Seven polypeptides 100, 90, 84, 80, 62, 19 and 12.5 kDa were absent in haemolymph and five 92, 90, 80, 60 and 55 kDa were absent in ovaries. Changes in the polypeptide pattern have been correlated with the fecundity reduction due to immunized blood feeding.

Animals↗

PubMed1990

[Autoradiographic study on the distribution of gonadotropin-releasing hormone receptor in the rat ovary].

Autoradiographic studies were undertaken to clarify the distribution and regulatory mechanisms of GnRH receptors in the ovary of the immature rat during sexual maturation. Iodinated GnRH analog (GnRHa) was injected intravenously and the uptake and distribution of the GnRHa in the ovary were examined. The uptake rate for GnRHa in the ovary increased gradually from 7 days to 21 days of age and declined by 49 days of age. The uptake of GnRHa increased in the ovary of the hypophysectomized rat (28 days old) treated with GnRH and decreased in those treated with PMSG. In the autoradiographic study, silver grains were detected in the ovary, that is the theca cells and the interstitial tissue as well as the granulosa cells. GnRHa bound predominantly to the interstitial tissues before 21 days of age, but GnRHa bound to the granulosa cells more than the theca cells and the interstitial tissue after 28 days of age, corresponding with the prepubertal decrease in GnRHa uptake in the ovary. These results suggest that the distribution of GnRH receptor in the ovary changes with follicular development during sexual maturation.

Animals↗

PubMedDate not supplied

[Effect of choriogonadotropin on the ovaries and uterus of infantile rats following treatment of the amygdaloid nuclei].

Experiments were conducted on female rats. The authors studied the effect of choriogonadotropin on the ovaries and uterus following simulation or destruction of the cortico-medial portion of the amygdaloid nuclei. In rats with an intact hypophysis administration of choriogonadotropin after stimulation or destruction of the amygdaloid nuclei led to increase in the number of the vesicular follicles and corpora lutea. In hypophysectomized rats the action on the amygdaloid nuclei failed to influence the choriogonadotropin effect on the ovaries. Changes in the ovaries depended on the total effect of choriogonadotropin and endogenous gonadotropins released into the blood after the action on the amygdaloid nuclei.

Amygdala↗

PubMedDate not supplied

Differential expression of tissue transglutaminase protein in mouse ovarian follicle.

Tissue transglutaminase (tTG) protein begins to accumulate in apoptotic cells and its mRNA is expressed at the onset of apoptotic change. In the present study, we compared tTG expression with the atretic degree of mouse ovarian follicles. The whole-body gamma-irradiated mouse ovaries were collected and immunohistochemistry for tTG and in situ 3'-end labeling (TUNEL) was performed. Based on the identification of atretic follicles with hematoxylin-eosin and TUNEL immunostaining, tTG expression was evaluated and compared between normal (NF) and atretic follicles (AF). The expression of tTG was different among AF depending on the degree of atretic changes. There was a strong association of tTG expression with the follicular apoptotic changes. Among NF, 24% of follicles expressed tTG protein. This value, however, increased up to 66% in atretic follicles. The present results suggest that the follicular expression of tTG is closely related to the degree of follicle atresia. Therefore, the expression of tTG can be used as a useful marker for the identification of atretic follicles in the ovary.

Analysis of Variance↗

PubMed1984

A comparative study of the follicular growth profile in conception and nonconception cycles.

To study the follicular growth profile of normal women, 25 multiparous volunteers were assessed daily by ultrasound to measure the growing follicle and underwent venipuncture daily for detection of the luteinizing hormone (LH) peak. Eleven subjects conceived during the first cycle, 1 during the second cycle, and 1 during the third cycle. The 15 cycles where conception was not achieved showed unequivocal signs of ovulation (i.e., an LH peak and progesterone concentrations in the luteal phase greater than 20 nM/l). The mean prerupture follicular diameter was not significantly different in either group, 19.65 mm and 19.1 mm, respectively; however, the growth profile showed marked differences with a stabilization of follicular growth 24 hours prior to rupture in all patients in the conception group. On the other hand, the LH peak occurred within the 24 hours immediately preceding follicular rupture in the conception cycles; whereas in the nonconception group, this time interval extended up to 48 hours prior to rupture.

Adult↗

PubMed1982

Ovulation detection in the human.

The importance of predicting human ovulation for either optimizing or avoiding conception has been considered from an endocrine, morphological and clinical view point. Of the biochemical markers in peripheral blood, a knowledge of the LH peak is the most clearly defined, with a two to four fold increase above baseline levels for a relatively short 24-30 hour preovulatory period. Ovulation is considered to occur 28-36 hours after the beginning of the LH rise or 8-20 hours after the LH peak. Daily assessment of the rise in preovular oestrogen reflects Graafian follicle development but the rise is less distinct and spread over 3-4 days with marked day to day fluctuations. LH induces a marked reduction in oestrogen production some 12 hours prior to ovulation and at the same time induces a two to three fold increase in progesterone production above baseline levels. While these changes in themselves are not great enough for day to day discrimination, a knowledge of their reciprocal relationship may be. The preovular rise in FSH is relatively small compared to LH and the radioimmunoassay technique has not generally been refined to be as rapid and reliable. Monitoring the day to day growth of the preovular follicle ultrasonically is both linear and potentially predictable but there is a wide range of its final diameter (17-26 mm) prior to ovulation making prediction inaccurate. With further refinements in ultrasonic resolution, detection of intrafollicular changes of the cumulus oophorus and granulosal cell layer configuration and thickness may give a closer prediction of the time of ovulation. At a clinical level a knowledge of menstrual cycle length in association with body messages which herald ovulation are useful and may forewarn that ovulation in terms of days is approaching. Such markers as preovulation pain, the detection of periovular cervical mucus and the change in physical character and position of the cervix are reliable signs of preovulation for many well motivated and informed women for either promoting or avoiding conception. A knowledge of the basal body temperature is not a prospective guide to ovulation, but once the thermal shift is established in association with loss of periovular mucus symptoms, the fertile period can be considered to have passed. Because we do not have a precise and simple marker of human ovulation, it is necessary that the most suitable marker of pre- or postovulation is chosen for the particular need in a given individual.

Body Temperature↗