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Endocrinology AND Infertility, female [keywords]
- Ovarian adult stem cells: hope or pitfall? [REVIEW]
- J Ovarian Res 2014.:71.
For many years, ovarian biology has been based on the dogma that oocytes reserve in female mammals included a finite number, established before or at birth and it is determined by the number and quality of primordial follicles developed during the neonatal period. The restricted supply of oocytes in adult female mammals has been disputed in recent years by supporters of postnatal neo-oogenesis. Recent experimental data showed that ovarian surface epithelium and cortical tissue from both mouse and human were proved to contain very low proportion of cells able to propagate themselves, but also to generate immature oocytes in vitro or in vivo, when transplanted into immunodeficient mice ovaries. By mentioning several landmarks of ovarian stem cell reserve and addressing the exciting perspective of translation into clinical practice as treatment for infertility pathologies, the purpose of this article is to review the knowledge about adult mammalian ovarian stem cells, a topic that, since the first approach quickly attracted the attention of both the scientific media and patients.
- Recruiting testicular torsion introduces an azoospermic mouse model for spermatogonial stem cell transplantation. [Journal Article]
- Urol J 2014; 11(3):1648-55.
Purpose:To investigate the long-term effect of testicular torsion on sperm parameters and testis structure in order to introduce a novel mice azoospermic model for spermatogonial stem cell transplantation. Materials and
Methods:Unilateral testicular torsion was created. The animals were divided into two groups each containing 15 mice. They underwent 2 and 4 hours of unilateral testicular ischemia, respectively. All animals in this experiment were aged matched. The experimental (n = 5) groups were studied 2, 4 and 10 weeks after testicular ischemia reperfusion. Moreover, the left testes and epididymis were removed for sperm analysis and for weight and histopathological evaluation. Finally isolated spermatogonial stem cells were transplanted in the testes that underwent 2 hours of ischemia reperfusion, two weeks post-surgery.
Results:All the investigated parameters demonstrated a sharp decline at 2, 4 and 10 weeks after testicular torsion, whereas 2-hour ischemia was found to be less injurious in testicular tissue structure. Two months after xenotransplantation, the transplanted cells were localized in the basal of the seminiferous tubules of the recipient ischemic testes.
Conclusion:Torsion can cause permanent azoospermia in mouse. Also Testicular torsion 2 weeks after the 2 hours ischemia reperfusion may prove useful for recipient preparation for SSCs transplantation in mouse.
- Association of PCOS and Its Clinical Signs with Sexual Function among Iranian Women Affected by PCOS. [JOURNAL ARTICLE]
- J Sex Med 2014 Jul 4.
Polycystic ovary syndrome (PCOS) and its physiological and psychological changes influence the sexual function of women affected.In the present study, we aimed to investigate the association of PCOS and its clinical signs with sexual function among a population of married Iranian women affected by PCOS.The impact of clinical signs of PCOS on sexual function of affected women was the main outcome measure in the present study.This cross-sectional study was carried out on 591 married women with PCOS, aged 18-45 years. Data were collected using a questionnaire including information on demographic and reproductive status and the Female Sexual Function Index. Data were analyzed using chi-square test, Mann-Whitney test, and logistic regression analysis.The participants' mean age was 30.6 years. Among associated manifestations of PCOS, infertility and hair loss have significant adverse effects on female sexual function. Logistic regression analysis showed that PCOS women with infertility have a significantly lower sexual function score compared with those who are fertile. Subgroup analysis demonstrated that compared with their fertile counterparts, PCOS women with infertility had significant sexual dysfunction in all aspects except desire and pain.Among various manifestations of PCOS, infertility mainly disrupts the sexual function of affected women. Hashemi S, Ramezani Tehrani F, Farahmand M, and Bahri Khomami M. Association of PCOS and its clinical signs with sexual function among Iranian women affected by PCOS. J Sex Med **;**:**-**.
- Nine centuries waiting: The experiences of Iranians surrogacy commissioning mothers. [Journal Article]
- Iran J Nurs Midwifery Res 2014 May; 19(3):224-32.
There are a few studies about commissioning mothers' understanding from the surrogacy during 9 months of waiting for delivery in Iran and other countries. This study was conducted with an aim to explore and explain the nature of concerns (experiences) of commissioning mothers.A qualitative design with a conventional content analysis approach was used to gather and analyze the experiences of commissioning mothers. They were selected from Royan Research Centre and other infertility centers in Iran. After purposive sampling for the selection of the participants, unstructured interviews were held for data collection. Twenty-four unstructured interviews were conducted with 12 commissioning mothers, 2 surrogate mothers, and 2 infertility center social workers who directly and continuously dealt with these mothers.TWO MAIN THEMES EMERGED FROM THE DATA ANALYSIS: 1. cultural dilemma (consisting of three subthemes: Social taboo, concerns about disclosure to others and the child, concerns about altering maternal and child's identity, and 2. uncertain waiting (consisting of three subthemes: Concerns about health of fetus and surrogate, concerns about an unfamiliar surrogate, and concerns about lack of preparation for maternal role).The study reveals the importance of maternal emotional care in this group and introduces a new arena for nurses' activity. These findings help the mothers by nurses' activities in health care clinics and anywhere they deliver nursing care.
- Molecular basis of thyrotropin and thyroid hormone action during implantation and early development. [REVIEW]
- Hum Reprod Update 2014 Jun 18.
Implantation and early embryo development are finely regulated processes in which several molecules are involved. Evidence that thyroid hormones (TH: T4 and T3) might be part of this machinery is emerging. An increased demand for TH occurs during gestation, and any alteration in maternal thyroid physiology has significant implications for both maternal and fetal health. Not only overt but also subclinical hypothyroidism is associated with infertility as well as with obstetric complications, including disruptions and disorders of pregnancy, labor, delivery, and troubles in early neonatal life.We searched the PubMed and Google Scholar databases for articles related to TH action on ovary, endometrium, trophoblast maturation and embryo implantation. In addition, articles on the regulation of TH activity at cellular level have been reviewed. The findings are hereby summarized and critically discussed.TH have been shown to influence endometrial, ovarian and placental physiology. TH receptors (TR) and thyrotropin (thyroid-stimulating hormone: TSH) receptors (TSHR) are widely expressed in the feto-maternal unit during implantation, and both the endometrium and the trophoblast might be influenced by TH either directly or through TH effects on the synthesis and activity of implantation-mediating molecules. Interestingly, due to the multiplicity of mechanisms involved in TH action (e.g. differential expression of TR isoforms, heterodimeric receptor partners, interacting cellular proteins, and regulating enzymes), the TH concentration in blood is not always predictive of their cellular availability and activity at both genomic and nongenomic level.In addition to the known role of TH on the hormonal milieu of the ovarian follicle cycle, which is essential for a woman's fertility, evidence is emerging on the importance of TH signaling during implantation and early pregnancy. Based on recent observations, a local action of TH on female reproductive organs and the embryo during implantation appears to be crucial for a successful pregnancy. Furthermore, an imbalance in the spatio-temporal expression of factors involved in TH activity might induce early arrest of pregnancy in women considered as euthyroid, based on their hormonal blood concentration. In conclusion, alterations of the highly regulated local activity of TH may play a crucial, previously underestimated, role in early pregnancy and pregnancy loss. Further studies elucidating this topic should be encouraged.
- Antimüllerian hormone and antral follicle count are lower in female cancer survivors and healthy women taking hormonal contraception. [JOURNAL ARTICLE]
- Fertil Steril 2014 Jun 13.
To determine the impact of hormonal contraception (HC) on markers of ovarian reserve, including antimüllerian hormone (AMH) and antral follicle count (AFC).Longitudinal prospective cohort.University hospital.Young adult female cancer survivors and healthy similar-age women.None.Participants were followed annually to determine hormone levels and for transvaginal ultrasound. Subjects who used HC within the preceding 3 months were considered to be exposed. Linear mixed effects models were used to incorporate repeated measures and adjust for potential confounders.A total of 249 women (126 survivors, 123 control subjects; average age 25.5 years) were followed for an average of 2.1 visits and 2.15 years. After adjusting for confounders, AMH was found to be 21% lower among survivors using HC and 55% lower among control subjects using HC (relative risk [RR] 0.79, 95% confidence interval [CI] 0.68-0.93; and RR 0.45, 95% CI 0.30-0.68; respectively). AFC was 20% lower among survivors and control subjects using HC (RR 0.80, 95% CI 0.69-0.93). When considering an individual subject, AMH was 17%-35% lower when a subject had recently used HC than when she had not (survivors: RR 0.83, 95% CI 0.75-0.93; control subjects: RR 0.65, 95% CI 0.55-0.78), and AFC was 11% lower (RR 0.89, 95% CI 0.82-0.96). Additive HC exposure across multiple visits was not associated with differences in AMH or AFC.AMH and AFC are significantly lower among women with recent exposure to HC. AMH and AFC should be interpreted with caution when measured in the setting of recent hormone use.
- Risk factors for recurrence rate of ovarian endometriomas following a laparoscopic cystectomy. [JOURNAL ARTICLE]
- Minerva Med 2014 Jun 10.
To evaluate risk factors those influence the recurrence of endometrioma after laparoscopic excision. Methods: A cross-sectional study was performed at Arash University Hospital between 2009 and 2011 on patients who had a minimum of one year of postoperative follow up after undergoing a laparoscopic excision of an ovarian endometrioma. The patients had any prior surgery for ovarian endometriomas was excluded. Recurrence was defined as the presence of endometrioma more than 2 cm in size, detected by ultrasonography within 1 years of surgery. The variables including age at surgery, presence of infertility, uterine myoma, previous medical treatment of endometriosis, the size of the largest cyst at laparoscopy, unilateral or bilateral involvement, serum CA125 level, revised American Society for Reproductive Medicine (ASRM) score and stage, postoperative medical treatment and postoperative treatment were evaluated to assess their independent effects on the recurrence using logistic regression analysis.A total one hundred fifty eight patients were admitted to surgery unit for endometriomas cystectomy during study period. After the initial assessment, 130 patients were eligible for study. The overall rate of recurrence was 11.5% (15/130). Significant factors that were independently associated with higher recurrence were the size of the largest cyst [odds ratio (OR) = 4.0, 95% confidence interval (95% CI) = 1.6-10.4, P = 0.002], a high rASRM score (OR = 1.2, 95% CI = 1.0-1.4, P = 0.04) and woman age at surgery (OR = 0.6, 95% CI = 0.4-0.9, P = 0.01).A high score of rASRM, large cyst size and young age at surgery were three significant factors that were associated with higher recurrence of endometriomas.
- Characterization of reproductive, metabolic and endocrine features of polycystic ovary syndrome in female hyperandrogenic mouse models. [JOURNAL ARTICLE]
- Endocrinology 2014 May 30.:en20141196.
Polycystic ovary syndrome (PCOS) affects 5-10% of women of reproductive age, causing a range of reproductive, metabolic and endocrine defects including: anovulation, infertility, hyperandrogenism, obesity, hyperinsulinism and an increased risk of type 2 diabetes and cardiovascular disease. Hyperandrogenism is the most consistent feature of PCOS, but its etiology remains unknown, and ethical and logistic constraints limit definitive experimentation in humans to determine mechanisms involved. In this study, we provide the first comprehensive characterization of reproductive, endocrine and metabolic PCOS traits in four distinct murine models of hyperandrogenism, comprising prenatal dihydrotestosterone (DHT, potent non-aromatizable androgen) treatment during days 16-18 of gestation, or long-term treatment (90 days from 21 days of age) with DHT, dehydroepiandrosterone (DHEA), or letrozole (aromatase inhibitor). Prenatal DHT treated mature mice exhibited irregular estrous cycles, oligo-ovulation, reduced preantral follicle health, hepatic steatosis and adipocyte hypertrophy, but lacked overall changes in body fat composition. Long-term DHT treatment induced polycystic ovaries displaying unhealthy antral follicles (degenerate oocyte and/or > 10% pyknotic granulosa cells), as well as anovulation and acyclicity in mature (16 week old) females. Long-term DHT also increased body and fat pad weights, and induced adipocyte hypertrophy and hypercholesterolemia. Long-term letrozole treated mice exhibited absent or irregular cycles, oligo-ovulation, polycystic ovaries containing hemorrhagic cysts atypical of PCOS, and displayed no metabolic features of PCOS. Long-term DHEA treatment produced no PCOS features in mature mice. Our findings reveal that long-term DHT treatment replicated a breadth of ovarian, endocrine and metabolic features of human PCOS, and provides the best mouse model for experimental studies of PCOS pathogenesis.
- Lgr4 gene regulates Corpus Luteum Maturation through Modulation of the WNT mediated EGFR-ERK Signaling Pathway. [JOURNAL ARTICLE]
- Endocrinology 2014 May 30.:en20132183.
Luteal phase insufficiency is one of the major causes of female infertility, but the molecular mechanisms are still largely unknown. Here we found that disruption of LGR4/GPR48, the newly identified receptor for R-spondins, greatly reduced female fertility in mice. The expression of Lgr4 was induced specifically in granulosa-lutein cells during luteinization. In Lgr4 deficient female mice, the estrous cycle was prolonged and serum progesterone levels were dramatically downregulated. In Lgr4(-/-) corpora lutea, the expression of key enzymes for steroidogenesis as well as common luteal marker genes was significantly decreased. Additionally, the activity of EGFR-ERK signaling was attenuated in Lgr4(-/-) granulosa-lutein cells. We found that the maturation of Lgr4(-/-) cells was impaired in cultured primary granulosa cells, but the defect was partially rescued by reactivation of EGFR signaling by HB-EGF treatment. We found that the expression of WNT/CTNNB1 downstream targets, including MMP9 which is a critical matrix metalloproteinase for activation of EGF-like factors, was significantly downregulated in Lgr4(-/-) ovaries. MMP9 inhibitor treatment attenuated hCG but not HB-EGF induced ERK activation and luteinization in primary granulosa cells. Together, we report that Lgr4 modulates WNT mediated EGFR-ERK signaling to facilitate corpus luteum maturation and ovarian steroidogenesis to maintain female reproduction.
- Implantation failure in female Kiss1(-/-) mice is independent of their hypogonadic state and can be partially rescued by leukemia inhibitory factor. [JOURNAL ARTICLE]
- Endocrinology 2014 May 30.:en20131916.
The hypothalamic kisspeptin signaling system is a major positive regulator of the reproductive neuroendocrine axis, and loss of Kiss1 in the mouse results in infertility; a condition generally attributed to its hypogonadotropic hypogonadism. We demonstrate that in Kiss1(-/-) female mice, acute replacement of gonadotropins and estradiol restores ovulation, mating and fertilization; however, these mice are still unable to achieve pregnancy because embryos fail to implant. Progesterone treatment did not overcome this defect. Kiss1(+/-) embryos transferred to a wild-type female mouse can successfully implant, demonstrating the defect is due to maternal factors. Kisspeptin and its receptor are expressed in the mouse uterus, and we suggest that it is the absence of uterine kisspeptin signaling that underlies implantation failure. This absence, however, does not prevent the closure of the uterine implantation chamber, proper alignment of the embryo and the ability of the uterus to undergo decidualization. Instead, the loss of Kiss1 expression specifically disrupts embryo attachment to the uterus. We observed that on the day of implantation, Lif, a cytokine that is absolutely required for implantation in mice, is weakly expressed in Kiss1(-/-) uterine glands and that the administration of exogenous Lif to hormone-primed Kiss1(-/-) female mice is sufficient to partially rescue implantation. Taken together, our study reveals that uterine kisspeptin signaling regulates glandular Lif levels, thereby identifying a novel and critical role for kisspeptin in regulating embryo implantation in the mouse. This study provides compelling reasons to explore this role in other species, particularly livestock and humans.