Changes In Ovarian Function Research Articles

Cigarette Smoke Exposure Elicits Increased Autophagy and Dysregulation of Mitochondrial Dynamics in Murine Granulosa Cells1

Cigarette smoking is a lifestyle behavior associated with significant adverse health effects, including subfertility and premature ovarian failure. Cigarette smoke contains a number of chemicals, many of which are involved in the generation of reactive oxygen species, which can lead to apoptosis and autophagy. Autophagy is a fundamental process that removes damaged organelles and proteins through lysosomal degradation. The relevance of autophagy to toxicant-induced changes in ovarian function is largely unexplored. Previously, we reported that exposure to cigarette smoke causes follicle loss, oxidative stress, activation of the autophagy pathway, and decreased expression of manganese superoxide dismutase, which points to altered mitochondrial function. Therefore, our objective here was to test whether exposure to cigarette smoke results in the dysregulation of mitochondrial repair mechanisms leading to loss of follicles via autophagy-mediated granulosa cell death. In this study, mice were exposed to cigarette smoke or room air for 8 wk. The expression of genes and proteins of autophagy and mitochondrial repair factors was measured using quantitative real-time PCR and Western blot analysis, immunohistochemistry, and enzyme-linked immunosorbent assay. Increased expression of parkin and decreased expression of the mitofusins suggest that exposure to cigarette smoke triggers mitochondrial damage. Moreover, the autophagy cascade proteins, BECN1 and LC3, were upregulated, whereas the antagonist BCL2 was downregulated, following treatment. Taken together, our results suggest exposure to cigarette smoke induces dysfunction of mitochondrial repair mechanisms, leading to autophagy-mediated follicle death.

Decreased ovarian function in premenopausal women is associated with increased central adiposity over ten years: the coronary artery risk development in young adult women's study

The perimenopause to menopause transition is associated with increased abdominal adiposity, potentially related to changes in sex steroid hormones. We hypothesized that earlier changes in ovarian function are associated with changes in adiposity. We assessed the associations of decreased ovarian reserve (DOR) with Δ in BMI and waist circumference (WC) over 10 years in pre-menopausal women.

Temporal window in which exposure to estradiol permanently modifies ovarian function causing polycystic ovary morphology in rats

To investigate the developmental window in which E(2) exposure produces irreversible changes in ovarian function resulting in polycystic ovary. Basic experimental study. University animal laboratory. Thirty Sprague-Dawley rats were administered a single E(2) valerate dose (10 mg/kg of weight) at 1, 7, 14, 21, or 30 days of age. Control rats were injected with the vehicle at 1 day of age. All rats were sacrificed at 6 months of age. Observation of vaginal opening, estrous cyclicity by vaginal smears, and ovarian morphometry in the 6-month-old rat. Measurement of ovarian noradrenaline by high-performance liquid chromatography coupled with electrochemical detection, serum levels of LH by enzyme-linked immunoassay, P, androstenedione, and E(2) by enzyme immunoassay. Rats exposed to E(2) at 1, 7, or 14 days of life did not show estrual cycling activity and maintained a polycystic ovary (PCO) condition throughout the entirety of the study. However, if the exposure to E(2) occurred after postnatal day 21, the PCO-induced condition was reversible. In rats that developed a permanent PCO condition, we observed significant effects of E(2) on ovarian morphology if exposure occurred on postnatal day 1 and a presumable effect on the hypothalamus if the exposure occurred between postnatal days 1 and 14. Our findings suggest that in rats, the most sensitive period for the promotion of an irreversible PCO morphology by estrogenic compounds is during neonatal early follicular development.

Fertility control of rodent pests: a review of the inhibitory effects of plant extracts on ovarian function

Plant extracts can inhibit fertility by adversely affecting, directly or indirectly, reproductive processes ranging from gonadal function and development to gestation. This review focuses on plant extracts that disrupt ovarian function in rodents. Extracts from at least 40 plant species exert some of their disruptive reproductive effects at the ovarian level. Of those, 13 plants induce a reduction in the number and type of ovarian follicles and also cause disruption to the oestrous cycle. Their effects are short term and reversible once treatment ceases. Protection of plant extracts to prevent their degradation before uptake in the gastrointestinal tract could enhance short-term efficacy but would not enhance the longevity of their effects. Identification and further testing of the specific chemicals responsible for reproductive effects would be beneficial. The adoption of a standard protocol for treatment and assessment of the inhibitory effects of potential control agents on reproductive function in rodents is essential. Treatment with higher concentrations of extracts in conjunction with other extracts or with other chemosterilants could have potential complementary effects and lead to more rapid and permanent changes in ovarian function. An orally delivered agent(s) that causes major depletion of all follicle types, and particularly of non-regenerating primordial follicles, could be an ideal fertility control product and serve as an additional tool for population control of pest rodents.

Changes in ovarian function and egg production in commercial broiler breeders through 40 weeks of lay

1. Egg production, body weight, feed intake and mortality were recorded in over 78 000 broiler breeder hens in 4 commercial flocks housed in 16 houses from early lay though 40 weeks of lay. A total of 420 hens were sampled at regular intervals throughout the laying period to determine the changes in body weight and the numbers of yellow follicles, paired follicles and hierarchical positions with time in the ovary throughout lay to relate ovarian function to productivity. Average egg weight was recorded weekly from one flock. 2. A quadratic equation fitted the changes in time for the number of yellow follicles, body weight, feed intake and mortality; a linear equation described the decline in the number positions in the hierarchy and there was a linear decline in the logistic scale of the proportions of yellow follicles developing as pairs of similar weight. Egg production was described by a cubic equation and egg weight by a line plus exponential model. 3. The average number of yellow follicles declined from 7·2 to 5·4 and the number of hierarchical positions from 6 to 5 from 4 to 40 weeks after photostimulation. The proportion of follicles developing as pairs of similar weight was over 25% at the onset of lay and declined to less than 10% from 20 weeks after photostimulation, representing a substantial loss of potential productivity. 4. Body weight and egg production were similar to the breeder's targets whereas average egg weight and mortality were higher than expected. 5. The relationship defining ovarian function will facilitate the development of an improved model of egg production in broiler breeder hens.

Changes in Ovarian Function after Radioactive Iodine among Patients with Differentiated Thyroid Carcinoma at St. Luke's Medical Center, Philippines

Objective. To determine the prevalence of menstrual and reproductive dysfunction among subjects who have undergone radioiodine treatment for thyroid carcinoma. Methodology. This study enrolled adult women with Differentiated Thyroid Carcinoma who received the treatment at age 40 years and below. Data was processed using SAS program and evaluated using Fischer’s test and Wilcoxon test. Results. The study enrolled 46 women. Three reported cycle irregularities, 4 reported changes in amount of bleeding and 1 had amenorrhea. The prevalence rate of menstrual abnormalities was 15.2%. These women received a significantly higher dose of radioactive iodine (RAI) (120 vs. 110 mCi, p = 0.0064). Eleven women tried to conceive and there were 5 births to 5 different subjects after radiation. There were no congenital anomalies and 1 miscarriage. Four women were menopausal with an average age of 44.4 years old. Conclusion. This study showed that the prevalence of menstrual disturbances after high dose radioactive iodine treatment among thyroid cancer patients is 15.2%. The affected group received a significantly higher dose of radioactive iodine compared to the unaffected group.

Impacto da embolização arterial do leiomioma uterino no volume uterino, diâmetro do mioma dominante e na função ovariana

To evaluate the impact of uterine artery embolization (UAE) on uterine volume (UV), greater myoma diameter (GMD) and ovarian function three months after the procedure, by transvaginal pelvic ultrasonography (TVPUS) and by the determination of follicle-stimulating hormone (FSH). Thirty patients with leiomyomas were submitted to UAE. TVPUS and FSH determination were performed before and three months after UAE. UV was determined in cm³, GMD in cm and FSH in IU/mL. Data are reported as as mean standard deviation (SD) and were analyzed statistically by the nonparametric Mann-Whitney test. Twenty-nine patients were analyzed. Before UAE, mean UV was 402.4 165.9 cm³ and GMD was 5.9 2.1 cm. After UAE, mean UV was 258.9 118.6 cm³ and GMD was 4.6 1.8 cm. Mean FSH concentration was 4.9 3.5 IU/mL before UAE and 5.5 4.7 IU/mL after UAE, with p=0.5. There was a 35% reduction of UV and a 22% reduction of GMD, with no changes in FSH values after three months. The procedure significantly reduced UV and GMD but did not cause a significant increase in FSH levels, thus causing no changes in ovarian function.

Differential effects of aging on estrogen negative and positive feedback

Recent studies have demonstrated an age-related decline in gonadotropins and a decrease in pituitary responsiveness to GnRH, indicating that aging influences the neuroendocrine components of the female reproductive axis independently of changes in ovarian function. To determine whether aging might also affect the luteinizing hormone (LH) negative and positive feedback responses to gonadal steroids, we administered a controlled, graded sex steroid infusion to 11 younger (45-56 yr) and nine older (70-80 yr) postmenopausal women (PMW) in whom endogenous ovarian steroids and peptides are uniformly low. The doses of estradiol (E(2)) and progesterone (P) were chosen to mimic levels across the normal follicular phase and have been shown previously to induce negative followed by positive feedback on LH. Similar E(2) and P levels were achieved in younger and older PMW (P = 0.4 and 0.3, respectively) and produced a biphasic LH response in all subjects. The early decline in LH to 53% of baseline was not different in older vs. younger PMW. However, the positive feedback effect was attenuated in older compared with younger PMW (peak LH 144.4 ± 19.5 vs. 226.8 ± 22.3 IU/l, respectively, P = 0.01). In conclusion, these studies in PMW demonstrate preservation of short-term steroid negative and positive feedback in response to exogenous E(2) and P with aging. Attenuation of positive feedback in older compared with younger PMW is consistent with previous reports of declining GnRH responsiveness with aging.

Bone mineral density loss during adjuvant chemotherapy in pre-menopausal women with early breast cancer: is it dependent on oestrogen deficiency?

Pre-menopausal women given adjuvant chemotherapy for breast cancer experience both premature ovarian failure and loss of bone mineral density (BMD), and this study was designed to see if these observations are causally linked. Chemotherapy was administered to 41 pre-menopausal women with early breast cancer enrolled prospectively in a study of ovarian function and BMD in such women given systemic therapy. After giving written informed consent, all patients underwent baseline and regular on-treatment measurements of BMD by dual-energy X-ray absorptiometry (DXA) scan, bone turnover and ovarian function by analysis of serum hormone levels and self-reported menstrual diaries. Baseline lumbar spine BMD in the 41 women given chemotherapy was higher than the normal population (Z score 0.28 ± 0.14 (mean ± SEM), P = 0.047), and fell significantly over the first 6 months from a mean of 1.05-1.01 g/m(2), P < 0.0001, and similar but smaller changes were demonstrated in hip BMD. This fall was independent of age at diagnosis, type of chemotherapy, development of amenorrhoea or either baseline or on-treatment estradiol concentration. During the 6 months after completion of adjuvant chemotherapy, BMD fell further only in those women with low estradiol or experiencing amenorrhoea during the first 6 months, although all groups showed evidence of increased bone turnover. This study demonstrates loss of both spine and hip BMD in pre-menopausal women during 6 months' adjuvant systemic chemotherapy to be independent of changes in ovarian function. Ovarian function was, however, related to BMD changes after chemotherapy ceased.

Influence of Nest Deprivation on Behaviour, Hormonal Concentrations and on the Ability to Resume Incubation in Domestic Hens (Gallus domesticus)

In this study, we investigated the influence of the length of nest deprivation period (3 vs. 6 d) on the ability to renest of incubating hens. We focused on the hens' behaviour, particularly on nesting and calls, on their prolactin, luteinizing hormone (LH) and oestradiol concentrations. Nest deprivation induced a drop of prolactin and an increase of LH plasmatic concentrations in hens. These changes in circulating pituitary hormones were followed by changes in ovarian function: the persistent rise of plasmatic oestradiol gave evidence of the resumption of ovarian activity. After nest deprivation, the number of clucks increased significantly and food calls appeared; these results demonstrate that ‘maternal’ calls can be emitted outside the maternal context. Our results suggest that the onset of typical maternal calling is strongly controlled by internal state such as plasmatic hormonal concentrations, independently of social stimulation. None of the 10 hens deprived for 6 d resumed incubation when given the opportunity, whereas, after a 3 d deprivation period, three out of 10 hens renested and two hens incubated sporadically and then gradually abandoned their nests. Long periods of nest deprivation appear to disrupt the habits of sitting and nesting. Before nest reopening, all the hens presented low levels of plasmatic prolactin. Plasma prolactin concentrations of the renesting hens increased after nest boxes were reopened and returned to levels found in incubating hens. We suggest that pituitary prolactin rather than plasmatic prolactin is responsible for the maintenance of incubating potential in hens deprived of their nests.

Female Mice Expressing Constitutively Active Mutants of FSH Receptor Present with a Phenotype of Premature Follicle Depletion and Estrogen Excess

Strong gain-of-function mutations have not been identified in humans in the FSH receptor (FSHR), whereas such mutations are common among many other G protein-coupled receptors. In order to predict consequences of such mutations on humans, we first identified constitutively activated mutants of the mouse (m) Fshr and then expressed them under the human anti-Müllerian hormone promoter in transgenic mice or created knock-in mutation into the mouse genome. We show here that mutations of Asp580 in the mFSHR significantly increase the basal receptor activity. D580H and D580Y mutations of mFSHR bind FSH, but the activity of the former is neither ligand-dependent nor promiscuous towards LH/human choriogonadotropin stimulation. Transgenic expression of mFshr(D580H) in granulosa cells leads to abnormal ovarian structure and function in the form of hemorrhagic cysts, accelerated loss of small follicles, augmented granulosa cell proliferation, increased estradiol biosynthesis, and occasional luteinized unruptured follicles or teratomas. The most affected mFshr(D580H) females are infertile with disturbed estrous cycle and decreased gonadotropin and increased prolactin levels. Increased estradiol and prolactin apparently underlie the enhanced development of the mammary glands, adenomatous pituitary growth, and lipofuscin accumulation in the adrenal gland. The influence of the mFSHR(D580Y) mutation is milder, mainly causing hemorrhagic cysts in transgenic mFSHR(D580Y) and mFSHR(D580Y) -knock-in mice. The results demonstrate that gain-of-function mutations of the FSHR in mice bring about distinct and clear changes in ovarian function, informative in the search of similar mutations in humans.

Is there a declining trend in ovarian function among infertility clinic patients?

There is a growing body of evidence that testicular function has decreased rapidly over the last 50 years. However, much less is known about corresponding trends in ovarian function. Herein, we examine the temporal changes in ovarian function in a large sample of infertile patients from the Czech Republic over a period of 14 years. In a retrospective study, we analysed a large body of data from women, 20-40 years of age, undergoing IVF/ICSI treatment between 1995 and 2008. We defined ovarian function using five variables: basal FSH level, estradiol (E2) level on the day of HCG administration, dose of gonadotrophins used for ovarian stimulation, number of retrieved oocytes and dose of gonadotrophins per oocyte. Controlling simultaneously for temporal changes in patient age and stimulation protocol, we applied generalized additive models to describe the temporal trends. During the study period the mean age of the study population increased by 2.7 years. Whereas the basal FSH and gonadotrophin dose did not change over time, the E2 level and oocyte retrieval declined, and the dose of FSH per oocyte increased during the study period. The results are indicative of a small, but detectable decrease in ovarian function over a period of 14 years, which is not causally related to the ageing population.

Melatonin-induced changes in ovarian function in the freshwater fish Channa punctatus (Bloch) held in long days and continuous light

It is possible to manipulate fish gonadal function through exogenous melatonin. However gonadal responses to melatonin vary and depend on time, mode and duration of the administration of the hormone. The present study describes the effects of different photoperiods and melatonin treatments on the ovarian kinetics of the fish Channa punctatus. Fish held in long days (LD 14:10) were injected melatonin daily (10 μg im) either at 08.00 or 17.00 h, respectively or immersed in melatonin water (100 μg/l) for 24 or 15 h daily. In another experiment fish held in long days or continuous light (LL; LD 24.00) were immersed in melatonin water (100 μg/l) either for 24 or 15 h daily. Both experiments had appropriate controls. The GSI (Gonadosomatic index = gonadal wt./100 g body weight) increased ( P < 0.01) in fish immersed in melatonin water daily for 24 h when compared either with the GSI of control fish or with fish held in melatonin water daily for 15 h (17.00–08.00 h). The GSI decreased ( P < 0.01) in fish that received melatonin daily by injection mode. Data from follicular kinetics largely corroborate the GSI data. Fish exposed to melatonin water daily for 24 h had more vitellogenic follicles (VF) and fewer atretic follicles (AF). There was a general decrease ( P < 0.01) in previtellogenic follicles (PVF) in all treated groups. Melatonin by injection mode did not affect the number of VF but it significantly increased ( P < 0.01) the AF. In the other experiment, the GSI increased ( P < 0.01) in fish held in long days and immersed in melatonin water 24 h daily. However, the GSI decreased in fish held in long days and immersed in melatonin water for a restricted period (between 17.00 and 08.00 h). The GSI of fish held in LL and immersed in melatonin water daily for 24 h increased ( P < 0.01), whereas it decreased ( P < 0.01) in fish that were immersed in melatonin water daily for 15 h. The data from follicular kinetics revealed a decrease in PVF of fish held in LL and in all the melatonin-exposed groups irrespective of the duration of exposure to melatonin. However the VF increased markedly in fish held in LL and immersed in melatonin water daily for 24 h. VF of fish held in LL but immersed in melatonin water daily for restricted period decreased. In fish held in long days and immersed in melatonin water daily either for 24 or 15 h the VF number increased ( P < 0.01). Marked increase in AF was seen fish held in LL and exposed to melatonin-containing water daily for restricted period. The effect of melatonin on reproduction seems to depend on the photoperiod and duration of exposure to melatonin. In fish held either in long days or LL, daily restricted exposure to melatonin tends to inhibit gonads, whereas continuous exposure to melatonin either stimulate or has no effect. The results apparently support the view that duration of exposure to melatonin signals darkness.

Effect of site of starch digestion on metabolic hormones and ovarian function in dairy cows

Delayed resumption of postpartum oestrous cycles in dairy cows is linked to low plasma insulin status and associated changes in ovarian function. Previous studies showed that plasma insulin can be raised by increasing dietary starch concentration, but it is not known if rumen digestible starch and bypass starch would be equally effective. The objective of the two experiments reported here was to investigate whether site of dietary starch digestion influences metabolic hormones and ovarian function. Cows were fed on a standard diet from calving until 40 days postpartum and then fed on treatment diets until 70 days postpartum. In Experiment 1, six cows were transferred to each of five diets with a starch content of 190 g/kg DM, of which 0.40, 0.45, 0.50, 0.55 or 0.60 was bypass starch. In Experiment 2, eight cows were transferred to each of four diets containing concentrates with low (L) or high (H) starch content and predominantly grass (G) or maize (M) silages in a factorial design. Between 60 and 70 days postpartum, plasma insulin was not influenced by site of starch digestion in Experiment 1, but insulin was increased by H ( P = 0.020) and M ( P = 0.048) in Experiment 2. Dietary bypass starch content negatively influenced plasma glucagon concentration ( P = 0.046) and the insulin to glucagon ratio ( P = 0.005) in Experiment 1. Growth hormone, insulin-like growth factor-I and leptin did not vary among diets in either experiment. The number of small (< 5 mm) ovarian follicles before ovulation tended ( P = 0.056) to decrease with increasing dietary bypass starch content and was negatively related ( P = 0.046) to plasma glucagon in Experiment 1, but there was no other dietary effect on ovarian function in either experiment. The main conclusion from these experiments is that rumen digestible starch and rumen bypass starch can be equally effective for maintaining plasma insulin and ovarian function of high-yielding dairy cows in early lactation.

Gender Differences in Mortality After Mitral Valve Operation: Evidence for Higher Mortality in Perimenopausal Women

Hormonal status is a potentially important cause for gender differences in outcomes after cardiovascular operations. Estrogen withdrawal states may potentiate ischemia-reperfusion injury by impairing endothelial cell function and increasing inflammatory cytokine levels. We hypothesized that gender influences mortality after mitral valve operations and that it varies with age, especially during periods of declining ovarian function. We studied 24,977 patients (49% women) in The Society of Thoracic Surgeons National Database who underwent isolated mitral valve repair or replacement from 2002 to 2005. Age-related gender differences in mortality after mitral valve operation were compared by risk-adjusted analysis. Gender and age had a pronounced impact on hospital mortality. Women aged 40 to 49 and 50 to 59 had significantly greater hospital mortality than risk-matched men. The adjusted female/male odds ratio for hospital mortality in the group aged 40 to 49 was 2.56 (95% confidence interval, 1.31 to 5.01) but progressively decreased in the four subsequent age groups. This pattern was statistically significant (p = 0.028 and p = 0.018 for 40 to 49 vs 70 to 79 and 80 to 89, respectively) and represents a declining relative mortality risk for women of advanced age. In patients aged 40 to 59 years, the mortality of mitral valve operation is approximately 2.5 times higher in women compared with men with similar risk factors. This survival disadvantage diminishes with further aging. Changes in ovarian function may be an important cause for this gender-age interaction and are a potential target for novel hormone-based therapies.

Ovarian Function After Uterine Fibroid Embolization

Uterine fibroid embolization (UFE) has come to be an effective alternative to myomectomy or hysterectomy. It has also been used to treat acute pelvic hemorrhage, postpartum bleeding, ectopic pregnancy, tumors, and vascular malformations. This study was an attempt to document the effects, if any, of UFE on ovarian hormonal status and menstruation up to 12 months after the procedure. UFE was carried out using polyvinyl alcohol particles in 60 women with an ultrasonographic diagnosis of uterine leiomyomas. Both uterine arteries were embolized under fluoroscopic guidance via a single femoral access. The goal was complete vascular occlusion. Circulating hormone levels were measured just before the procedure and 3 and 12 months afterward on days 2 and 5 of the menstrual cycle. Ovarian failure was defined as a follicle-stimulating hormone (FSH) level exceeding 30 IU/liter. UFE was technically successful in all instances. Patients were followed up for 18 months on average. Women younger than 45 years (group 1) had no significant change in serum FSH levels at any time, but older women (group 2) had significantly increased levels 3 and 12 months after UFE. Luteinizing hormone levels similarly were significantly increased after UFE in group 2 patients only. Serum estradiol levels were similar before and after UFE in group 1 patients, but were significantly decreased postoperatively in group 2 women. The rate of clinical and laboratory ovarian failure was 31%. Fourteen of these 19 patients had permanent ovarian failure, and all but one of them (92%) were more than 45 years of age. Women less than 45 years old appear able to undergo UFE for the treatment of uterine fibroids with little, if any, change in ovarian function. In older women, however, ovarian function may be compromised.

Genes invoked in the ovarian transition to menopause

Menopause and the associated declines in ovarian function are major health issues for women. Despite the widespread health impact of this process, the molecular mechanisms underlying the aging-specific decline in ovarian function are almost completely unknown. To provide the first gene–protein analysis of the ovarian transition to menopause, we have established and contrasted RNA gene expression profiles and protein localization and content patterns in healthy young and perimenopausal mouse ovaries. We report a clear distinction in specific mRNA and protein levels that are noted prior to molecular evidence of steroidogenic failure. In this model, ovarian reproductive aging displays similarities with chronic inflammation and increased sensitivity to environmental cues. Overall, our results indicate the presence of mouse climacteric genes that are likely to be major players in aging-dependent changes in ovarian function.

Short photoperiod-induced ovarian regression is mediated by apoptosis in Siberian hamsters (Phodopus sungorus)

Siberian hamster reproduction is mediated by photoperiod-induced changes in gonadal activity. However, little is known about how photoperiod induces cellular changes in ovarian function. We hypothesized that exposing female hamsters to short (inhibitory) as opposed to long (control) photoperiods would induce an apoptosis-mediated disruption of ovarian function. Ovaries and plasma from hamsters exposed to either long (LD, 16 h light:8 h darkness) or short (SD, 8 h light:16 h darkness) days were collected during diestrus II after 3, 6, 9 and 12 weeks and processed for histology or RIA respectively. Apoptosis was assessed by in situ TUNEL and active caspase-3 protein immunolabeling. No significant differences were observed among LD hamsters for any parameter; therefore, these control data were pooled. SD exposure induced a decline in preantral follicles (P < 0.05), early antral/antral follicles (P < 0.01) and corpora lutea (P < 0.01) by week 12 as compared with LD. Terminal atretic follicles appeared by SD week 9; by week 12, these had become the predominant ovarian structures. Estradiol concentrations decreased by weeks 9 and 12 SD when compared with both LD and week-3 SD hamsters (P < 0.05); however, no changes were observed for progesterone. TUNEL-positive follicles in SD ovaries increased at week 3 and subsequently declined by week 12 as compared with LD ovaries (P < 0.01). Active capsase-3 protein immunostaining peaked at SD week 3 as compared with all other groups (P < 0.01). TUNEL and capsase-3 immunolabeling were localized to granulosa cells of late-preantral and early-antral/antral follicles. These data indicate that SD exposure rapidly induces follicular apoptosis in Siberian hamsters, which ultimately disrupts both estradiol secretion and folliculogenesis, resulting in the seasonal loss of ovarian function.

Effects of dehydroepiandrosterone on ovarian cystogenesis and immune function

The purpose of the present report was to study the possible relationship between ovarian functionality and the immune response during cystogenesis induced by androgenization with dehydroepiandrosterone (DHEA). Daily injection of DHEA (6 mg/kg body weight) for 20 consecutive days induced ovarian cysts in BALB/c mice. As markers of ovarian function, serum estradiol (E) and progesterone (P) and the ovarian inmunomodulator prostaglandin E (PGE) were analyzed. In order to know how the integrity of the tissue was altered after induction of cystogenesis, the oxidative status was also evaluated. Serum E and P levels, and ovarian PGE concentration, were increased in animals with cysts compared with healthy controls. The oxidant status (quantified by malondialdehyde (MDA) formed after the breakdown of the cellular membrane by free radical mechanisms) was augmented, meanwhile the antioxidant (evaluated by the glutathione (GSH) content) diminished during the induction of cystogenesis. Both immunohistochemical and flow cytometry assays demonstrated that DHEA treatment increased the number of T lymphocytes infiltrating ovarian tissue. Therefore, while ovarian controls showed equivalent expression of CD4+ and CD8+ T cell subsets, injection of DHEA yielded a selective ovarian T cell infiltration as demonstrated by enhanced CD8+ and diminished CD4+ T lymphocyte expression. These results show that the development of cysts involves changes in ovarian function and an imbalance in the oxidant–antioxidant equilibrium. We observed also both an increased and selective T lymphocyte infiltration.

Risk of uterine leiomyomata in relation to tobacco, alcohol and caffeine consumption in the Black Women's Health Study.

Tobacco, alcohol and caffeine consumption may influence risk of uterine leiomyomata via changes in ovarian function or hormone metabolism. We prospectively assessed the relation of these exposures to risk of self-reported uterine leiomyomata in the Black Women's Health Study. From 1997 to 2001, we followed 21,885 premenopausal women with intact uteri and no prior myoma diagnosis. Cox regression models were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs). During 73,426 person-years of follow-up, 2177 incident cases of uterine leiomyomata confirmed by ultrasound (n = 1920) or hysterectomy (n = 257) were reported. Cigarette smoking was not associated with risk of uterine leiomyomata. Risk was positively associated with years of alcohol consumption and current consumption of alcohol, particularly beer. Relative to non-drinkers, multivariate IRRs for beer consumption of < 1, 1-6 and 7+ drinks/week were 1.11 (95% CI 0.98-1.27), 1.18 (95% CI 1.00-1.40) and 1.57 (95% CI 1.17-2.11), respectively. Heavy coffee and caffeine consumption were not associated with risk overall, but IRRs were increased among women aged < 35 years. In US black women, risk of uterine leiomyomata was positively associated with current consumption of alcohol, particularly beer. Cigarette smoking and caffeine consumption were unrelated to risk overall.