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Infertility female [keywords]
- Over-expression of Corticotropin Releasing Factor in the Central Nucleus of the Amygdala Advances Puberty and Disrupts Reproductive Cycles in Female Rats. [JOURNAL ARTICLE]
- Endocrinology 2014 Jul 22.:en20141339.
Prolonged exposure to environmental stress activates the hypothalamic-pituitary-adrenal (HPA) axis and generally disrupts the hypothalamic-pituitary-gonadal (HPG) axis. As corticotropin-releasing factor (CRF) expression in the central nucleus of the amygdala (CeA) is a key modulator in adaptation to chronic stress, and central administration of CRF inhibits the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator, we tested the hypothesis that over-expression of CRF in the CeA of female rats alters anxiety behaviour, dysregulates the HPA axis response to stress, changes pubertal timing and disrupts reproduction. We used a lentiviral vector to increase CRF expression site specifically in the CeA of pre-weaning (postnatal day 12) female rats. Over-expression of CRF in the CeA increased anxiety-like behavior in peripubertal rats shown by a reduction in time spent in the open arms of the elevated plus maze and a decrease in social interaction. Paradoxically, puberty onset was advanced, but followed by irregular estrous cyclicity and an absence of spontaneous preovulatory LH surges associated with proestrous vaginal cytology in rats over-expressing CRF. Despite the absence of change in basal or stress (lipopolysaccharide or restraint) induced corticosterone secretion, over-expression of CRF in the CeA significantly decreased lipopolysaccharide, but not restraint, stress-induced suppression of pulsatile LH secretion in post pubertal ovariectomized rats, indicating a differential stress responsivity of the GnRH pulse generator to immunological stress and a potential adaptation of the HPA axis to chronic activation of amygdaloid CRF. These data suggest that the expression profile of this key limbic brain CRF system might contribute to the complex neural mechanisms underlying the increasing incidence of early onset of puberty on the one hand and infertility on the other attributed to chronic stress in modern human society.
- Pigment epithelium derived factor (PEDF) in the reproductive system. [JOURNAL ARTICLE]
- Reproduction 2014 Jul 21.
The physiological function of the female reproductive organs is hormonally controlled. In each cycle the reproductive organs undergo tissue modifications that are accompanied by formation and destruction of blood vessels. Proper angiogenesis requires an accurate balance between stimulation and inhibition of angiogenesis, maintained by pro- and anti-angiogenic factors. As with many other tissues, vascular endothelial growth factor (VEGF) appears to be one of the major pro-angiogenic factors in the female reproductive organs. Pigment epithelium-derived factor (PEDF) is a non-inhibitory member of the serine protease inhibitors (serpin) superfamily, possessing potent physiologic anti-angiogenic activity that negates VEGF activity. The anti-angiogenic effect of PEDF has been extensively investigated in the eye and in cancer, demonstrating its role in decreasing abnormal neovascularization, mainly by inhibiting the stimulatory activity of several strong pro-angiogenic factors, including VEGF. This review summarizes the function of PEDF in the reproductive system, showing its hormonal regulation and its anti-angiogenic activity. Furthermore, some pathologies of the female reproductive organs, including endometriosis, ovarian hyperstimulation syndrome (OHSS), polycystic ovary syndrome (PCOS), and others, are associated with a faulty angiogenic process; therefore, this review illuminates the role of PEDF in their pathogenesis and treatment. Collectively, we can conclude that although PEDF seems to play an essential role in the physiology and pathophysiology of the reproductive system its full role and mechanism of action still need to be illustrated.
- Laparoscopic Dissection and Anatomy of Sacral Nerve Roots and Pelvic Splanchnic Nerves. [JOURNAL ARTICLE]
- J Minim Invasive Gynecol 2014 Jul 15.
to demonstrate the technique of laparoscopic dissection for identification of sacral nerve roots and pelvic splanchnic nerves.case report.Classification: Canadian Task Force Classification III.private practice hospital in São Paulo, Brazil.31-years old female patient with suspected iatrogenic and/or compression of sacral nerve roots. She had debilitating pelvic, gluteal and perineal unilateral left pain (score 8, pain scale 0-10), and primary infertility with one previous failed IVF attempt. Surgical history included laparoscopic excision of endometriosis 10 months before the procedure, and a left ooforoplasty during adolescence for a benign neoplasm.Standard 4-puncture laparoscopy was established. Peritoneum of the left pelvic sidewall was resected to eradicate eventual residual endometriosis. This also allowed for the identification of uterine vessels, including the deep uterine vein, which is the limit between the pars vascularis (superiorly) and pars nervosa (inferiorly) in the uterine broad ligament. Surgery was based in the LANN (laparoscopic neuronavigation) technique, previously described by one of the authors. For identification of the sacral roots, dissection began medial to the ureter and lateral to the uterosacral ligament. Okabayashi's pararectal space was developed as deepest as possible by blunt dissection in avascular spaces. Hemostasis was performed with 5-mm bipolar forceps, and harmonic energy was not used. The hypogastric fascia was entered from medial to lateral, and the piriformis muscle was identified. The sacral nerve root S1 was identified lying over it. Dissection then proceeded caudally, and sacral roots S2 and S3 were sequentially identified. Small and delicate fibers forming the pelvic splanchnic nerves were isolated emerging from sacral roots S2 and S3. Other nerve fibers were identified caudally, probably representing pelvic splanchnic nerves emerging from S4.surgery lasted 70 minutes and bleeding was minimal. There was no suspected compression or iatrogenic injury identified. Patient was discharged in the following day. After 8 months of follow-up, she had partial recovery of pain (score 5, pain scale 0 to 10), and another failed IVF attempt, attributed to unsatisfactory quality of the embryos. There were no symptoms or dysfunctions attributable to manipulation of the nerves.laparoscopy is a useful tool to identify sacral roots and pelvic splanchnic nerves for suspected diseases. Its applications in the field of neuropelveology can be expanded by proper knowledge and training.
- Exogenous Leptin Administered Intramuscularly Induces Sex Hormone Disorder and Ca Loss via Downregulation of Gnrh and PI3K Expression. [JOURNAL ARTICLE]
- Exp Anim 2014 Jul 22.
Obesity is a public health problem that increases the risk of metabolic disease, infertility, and other chronic health problems. The present study aimed to develop a new rat model for sex hormone disorder with overweight and Ca loss by intramuscular injection of exogenous leptin (LEP). Thirty female Sprague-Dawley (SD) rats (40 days old) were injected thrice intramuscularly with LEP or keyhole limpet hemocyanin immunogen. The following analyses were performed to determine the development of appetite, overweight, reproductive related-hormones, and calcium (Ca)/phosphorus (Pi) in SD rats: measurement of Lee's index, body weight, food intake; serum Ca, Pi, and hormone tests by enzyme-linked immunosorbent analysis; histological analysis of abdominal fat; real-time polymerase chain reaction analysis of neuropeptide Y, pro-opiomelanocortin, gonadotropin-releasing hormone (Gnrh) mRNA, and gonadotropin-releasing hormone receptor (Gnrhr) mRNA expression; and western blotting analysis of enzyme phosphatidylinositol-3-kinase (PI3K). Rats injected with LEP immunogen displayed significantly increased body weight, food intake, Lee's index, serum LEP, serum cortisol, fat deposition in the abdomen, and decreased hormones including follicle stimulating hormone, luteinizing hormone, estradiol, cholecystokinin, and Ca. Exogenous LEP administered intramuscularly also downregulate Gnrh and PI3K. In conclusion, exogenous LEP administered intramuscularly is a novel animal model for sex hormones disorder with overweight and Ca loss in SD rats. The downregulation of PI3K and Gnrh may be involved in the development of this animal model.
- Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis. [JOURNAL ARTICLE]
- Nat Commun 2014.:4478.
Endometriosis is a common gynaecological disease associated with pelvic pain and infertility. Current treatments include oral contraceptives combined with nonsteroidal anti-inflammatory drugs or surgery to remove lesions, all of which provide a temporary but not complete cure. Here we identify an endometriosis-targeting peptide that is internalized by cells, designated z13, using phage display. As most endometriosis occurs on organ surfaces facing the peritoneum, we subtracted a phage display library with female mouse peritoneum tissue and selected phage clones by binding to human endometrial epithelial cells. Proteomics analysis revealed the z13 receptor as the cyclic nucleotide-gated channel β3, a sorting pathway protein. We then linked z13 with an apoptosis-inducing peptide and with an endosome-escaping peptide. When these peptides were co-administered into the peritoneum of baboons with endometriosis, cells in lesions selectively underwent apoptosis with no effect on neighbouring organs. Thus, this study presents a strategy that could be useful to treat peritoneal endometriosis in humans.
- The appearance of the endometrium at saline contrast sonohysterography in the luteal phase of the menstrual cycle: a prospective observational study. [JOURNAL ARTICLE]
- Ultrasound Obstet Gynecol 2014 Jul 9.
To describe the ultrasonographic morphology of the endometrium at saline contrast sonohysterography (SCSH) performed in the luteal phase of the menstrual cycle in women 20 - 38 years old with regular menstrual cycles.The study includes 26 women (median age 33 years, range 20 - 38) with regular menstrual cycles referred for hystero-contrast-salpingo-sonography (HyCoSy) as part of infertility work-up (n =19) or before donor insemination in female homosexual couples (n = 7). SCSH and HyCoSy were performed 6 - 10 days after a positive luteinizing hormone (LH) urinary self-test. Three-dimensional (3D) ultrasound volumes of the uterus were saved with and without saline in the uterine cavity. The results presented are based on off-line analysis of the 3D volumes.Median endometrial thickness was 10.4 mm (range 6.0 - 17.3 mm). Twelve (46%, 95%CI 27 - 65) of the 26 women had endometrial folds at SCSH. The number of folds varied between 1 and 6 (median 3). Endometrial thickness was similar in women with and without endometrial folds (median endometrial thickness 10.7 mm, range 6.0 - 17.3 versus 10.1 mm, range 6.1 - 14.4; P = 0.257), and the amount of saline in the uterine cavity did not differ between the two groups (median 8.6 mm, range 5.2 - 12.9 vs 7.1 mm, range 3.2 - 13.3; P = 0.527). In two women with endometrial folds at 2D or 3D SCSH focal endometrial pathology (polyp) was suspected but hysteroscopically resected endometrium showed normal histology.One should avoid performing SCSH in the luteal phase of the menstrual cycle, not only because there may be a fertilized ovum in the genital tract, but also because endometrial folds are common in this phase and may lead to overdiagnosis of focal endometrial pathology such as polyps. If - for some reason - SCSH is performed in the luteal phase and results are equivocal, the procedure should be repeated in the follicular phase.
- Evaluating the physiological and behavioral response of a male and female gorilla (Gorilla gorilla gorilla) during an introduction. [JOURNAL ARTICLE]
- Zoo Biol 2014 Jul 14.
Prolonged stress responses can lead to infertility and death; therefore monitoring respective indicators like stress-related hormones and behaviors is an important tool in ensuring the health and well-being among zoo-housed animal populations. Changes in social structure, such as the introduction of a new conspecific, can be a source of stress. In April 2010, a sexually mature female western lowland gorilla (Gorilla gorilla gorilla) was brought to Lincoln Park Zoo (LPZ; Chicago, IL) from the Chicago Zoological Park (Brookfield, IL) for a breeding recommendation from the Gorilla Species Survival Plan®. Fecal glucocorticoid metabolites (FGMs) were monitored in two gorillas prior to, during and immediately following the social introduction. Reproduction events, such ovarian cyclicity and pregnancy, were monitored using behavior and fecal progestagen metabolite (FPM; female) and fecal androgen metabolite (FAM; male) analyses. Mean (± standard error) FGM concentrations for the male were elevated (P = 0.002) during the introduction (20.61 ± 0.83 ng/g) compared to the pre- and post-introduction phases (11.31 ± 0.48 ng/g and 12.42 ± 0.65 ng/g, respectively). For the female, mean FGM concentrations were lower (P < 0.001) during the post-introduction (17.91 ± 1.07 ng/g) than during the pre- and introduction phases (30.50 ± 3.42 and 27.38 ± 1.51 ng/g, respectively). The female maintained normal FPM cyclicity throughout the study and became pregnant in the post-introduction phase. These results suggest the importance of both behavioral and physiological monitoring of zoo animals and demonstrate the potential stress that can occur during social introductions. Zoo Biol. XX:XX-XX, 2014. © 2014 Wiley Periodicals, Inc.
- Reproductive and menstrual factors and risk of differentiated thyroid carcinoma: The EPIC study. [JOURNAL ARTICLE]
- Int J Cancer 2014 Jul 8.
Differentiated thyroid carcinoma (TC) is 3-fold more common in women than in men and, therefore, a role of female hormones in the aetiology of differentiated TC has been suggested. We assessed these hypotheses in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among 345,157 women (mean age: 51) followed for an average of 11 years, 508 differentiated TC cases were identified. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression models. No significant associations were observed between differentiated TC risk and number of pregnancies, breast feeding, menopausal status, and age at menarche and at menopause. Significant associations were found with history of infertility problems (HR 1.70; 95% CI 1.12-2.60), a recent pregnancy (HR for ≤5 vs >5 years before recruitment 3.87; 95% CI 1.43-10.46), menopause type (HR for surgical vs natural menopause: 2.16; 95% CI 1.41-3.31), oral contraceptive (OC) use at recruitment (HR: 0.48; 95% CI 0.25-0.92), and duration of OC use (HR for ≥9 vs ≤1 year: 0.66; 95% CI: 0.50-0.89). An increased risk was also found with hormone replacement therapy use at recruitment (HR = 1.30, 95% CI 1.02-1.67), but this was not significant after adjustment for type of menopause (HR = 1.22, 95% CI 0.95-1.57). Overall, our findings do not support a strong role of reproductive and menstrual factors, and female hormone use in the aetiology of differentiated TC. The few observed associations may be real or accounted for by increased surveillance in women who had infertility problems, recent pregnancies or underwent surgical menopause. © 2014 Wiley Periodicals, Inc.
- Evaluation of uterine myomas during pregnancy using magnetic resonance imaging. [JOURNAL ARTICLE]
- Neuro Endocrinol Lett 2014 Jul 20; 35(4)
Patients with infertility commonly undergo various diagnostic and therapeutic procedures that may affect the future course of the pregnancy. In this presented case a female patient with infertility has been subjected to laparoscopic myomectomy and chromoscopy of the fallopian tubes, as it turned out later, 4 days after spontaneous conception. Due to severe pain in the 19th week of pregnancy the uterus area with the scar resulted from the removed myoma was visualised by magnetic resonance imaging (MRI). The MRI showed an active red degeneration in one of the myomas. At the same time the thickness of the uterus wall in previous myomectomy area was normal. The control MRI performed in the 36th week of pregnancy showed a hyaline degeneration of the myoma, underlying its dynamic refraction. The MRI approach enabled a non-invasive treatment and delivery in term.
- The Role of SPRASA in Female Fertility. [JOURNAL ARTICLE]
- Reprod Sci 2014 Jul 18.
Fertility is a complex process and infertility can have many causes. Sperm protein reactive with antisperm antibody (SPRASA)/sperm lysozyme-like protein 1 is a protein discovered as the target of autoantibodies in infertile men and previously thought to be expressed only in sperm. Using a bovine in vitro fertilization model, we have shown that SPRASA antiserum reduced sperm binding to zona-free oocytes and the development of embryos to morulae but did not affect the postfertilization cleavage rate to 2 cells or sperm motility. We demonstrated that SPRASA was expressed in ovarian follicles, corpora lutea, and oocytes by a combination of reverse transcription-polymerase chain reaction and immunohistochemistry. Female mice immunized with SPRASA had profound infertility following timed matings and those mice that did become pregnant had reduced fetal viability. The levels of antibodies reactive with SPRASA in 204 fertile and 202 infertile couples were elevated in 3 infertile but no fertile women. Together, these results indicate that SPRASA has a role in female fertility.