Endocrinology AND Infertility, female [keywords]
- Molecular characterization of insulin resistance and glycolytic metabolism in the rat uterus. [Journal Article]
- Sci Rep 2016.:30679.
Peripheral insulin resistance and hyperandrogenism are the primary features of polycystic ovary syndrome (PCOS). However, how insulin resistance and hyperandrogenism affect uterine function and contribute to the pathogenesis of PCOS are open questions. We treated rats with insulin alone or in combination with human chorionic gonadotropin (hCG) and showed that peripheral insulin resistance and hyperandrogenism alter uterine morphology, cell phenotype, and cell function, especially in glandular epithelial cells. These defects are associated with an aberration in the PI3K/Akt signaling pathway that is used as an indicator for the onset of insulin resistance in classical metabolic tissues. Concomitantly, increased GSK3β (Ser-9) phosphorylation and decreased ERK1/2 phosphorylation in rats treated with insulin and hCG were also observed. We also profiled the expression of glucose transporter (Glut) isoform genes in the uterus under conditions of insulin resistance and/or hyperandrogenism. Finally, we determined the expression pattern of glycolytic enzymes and intermediates during insulin resistance and hyperandrogenism in the uterus. These findings suggest that the PI3K/Akt and MAPK/ERK signaling pathways play a role in the onset of uterine insulin resistance, and they also suggest that changes in specific Glut isoform expression and alterations to glycolytic metabolism contribute to the endometrial dysfunction observed in PCOS patients.
- Is there a role for diet in ameliorating the reproductive sequelae associated with chronic low-grade inflammation in PCOS and obesity? [REVIEW, JOURNAL ARTICLE]
- Fertil Steril 2016 Jul 20.
A 2013 ASRM committee opinion titled "Optimizing natural fertility" stated that "there is little evidence that dietary variations such as vegetarian diets, low-fat diets, vitamin-enriched diets, antioxidants, or herbal remedies improve fertility …." However, there are emerging epidemiologic data demonstrating that certain components of the diet may influence reproductive health outcomes. Furthermore, translational work with human specimens and animal models lends biologic plausibility to the epidemiologic data, particularly in the context of female reproductive diseases associated with inflammation, including polycystic ovary syndrome (PCOS) and obesity. How to best apply these data clinically for improved reproductive outcomes remains to be determined. In this review, we outline a role for chronic inflammation in the reproductive sequelae of PCOS and obesity and we summarize epidemiologic and translational work demonstrating a potential role for diet in the regulation of inflammatory processes associated with these disorders. These studies identify areas for future research and potential clinical intervention in women affected by the reproductive sequelae of PCOS and obesity.
- Bone in The Endometrium: A Review. [Journal Article, Review]
- Int J Fertil Steril 2016 Jul-Sep; 10(2):154-61.
To provide a comprehensive review of the published literature of patients with endo- metrial bone or osseous fragments with a view to critically examine the antecedent clinical presentation, investigations and prognosis after treatment. This systematic review of the literature includes full text articles of published case re- ports and cases series from the following computerized databases: PubMed, Ovid, and Medline between 1928 and 2013. We reviewed a total of 293 patients in 155 case reports and case series. The mean ± SD age at presentation was 32.7 ± 8.9. Approximately 88% of patients had at least one prior surgical uterine evacuation relating to pregnancy termina- tion or loss at a median gestational age of 14 weeks (range of 4-41 weeks). The most common presenting symptom was infertility (56.2%). One hundred twenty- four (66.0%) of the 188 patients attempting pregnancy after treatment achieved pregnancy prior to article publication and the majority (82.3%) were spontane- ous. Spontaneous miscarriage rate remains high (43%); however, most pregnancies ended in live-birth (55%). Bone fragments in the endometrium are most commonly found after pregnancy termina- tion, present with infertility and/or irregular menses, and upon removal, patients rapidly conceive spontaneously.
- Methylation Status of H19/IGF2 Differentially Methylated Region in in vitro Human Blastocysts Donated by Healthy Couples. [JOURNAL ARTICLE]
- Iran Biomed J 2016 Jul 19.
Backgrund: Imprinted genes are a unique subset of few genes, which have been differentially methylated region (DMR) in a parental origin-dependent manner during gametogenesis, and these genes are highly protected during pre-implantation epigenetic reprogramming. Several studies heve shown that the particular vulnerability of imprinting genes during suboptimal pre- and peri-conception microenvironments often occur by assisted reproduction techniques (ART). This study investigated the methylation status of H19/IGF2 DMR at high-quality expanding/expanded human blastocysts donated by healthy individuals to evaluate the risks linked to ART.Methylation levels of H19/IGF2 DMR were analyzed by bisulfite conversion and sequencing at 18 CpG sites (CpGs) located in this region.Results showed that the overall percentage of methylated CpGs and the proportion of hyper-methylated clones of H19/IGF2 DMR in analyzed blastocysts were 37.85±4.87% and 43.75±5.1%, respectively. For validation of our technique, the corresponding methylation levels of peripheral human lymphocytes were defined (49.52±1.86% and 50%, respectively).Considering the absence of in vivo produced human embryos, it is not possible to conclude that the methylation found in H19/IGF2 DMR is actually normal or abnormal. Regarding the possible risks associated with ART, the procedures should be optimized in order to at least reduce some of the epigenetic risks.
- Concepts in diagnosis and therapy for male reproductive impairment. [REVIEW, JOURNAL ARTICLE]
- Lancet Diabetes Endocrinol 2016 Jul 6.
An accurate medical history and directed physical examination are essential in diagnosis of male infertility. We review the hormonal assessments and specific genetic analyses that are useful additional tests, and detail other evidence-based examinations that are available to help guide therapeutic strategies. By contrast with female infertility treatments-especially hormonal manipulations to stimulate or enhance oocyte production-spermatogenesis and sperm quality abnormalities are much more difficult to affect positively. In general, a healthy lifestyle can improve sperm quality. A few men have conditions in which evidence-based therapies can increase their chances for natural conception. In this second of two papers in The Lancet Diabetes and Endocrinology Series on male reproductive impairment, we examine the agreements and controversies that surround several of these conditions. When we are not able to cure, correct, or mitigate the cause of conditions such as severe oligozoospermia, non-remedial ductal obstruction, and absence of sperm fertilising ability, assisted reproductive technologies, such as in-vitro fertilisation (IVF) with intracytoplasmic sperm injection (ICSI), can be used as an adjunctive measure to allow for biological paternity. Not considered possible just two decades ago, azoospermia due to testicular failure, including 47,XXY (Klinefelter syndrome), is now treatable in approximately 50% of cases when combining surgical harvesting of testicular sperm and ICSI. Although genetic fatherhood is now possible for many men previously considered sterile, it is crucial to discover and abrogate causes as best possible, provide reliable and evidenced-based therapy, consider seriously the health and wellness of any offspring conceived, and always view infertility as a possible symptom of a more general or constitutional disease.
- A Validated Normative Model for Human Uterine Volume from Birth to Age 40 Years. [Journal Article]
- PLoS One 2016; 11(6):e0157375.
Transabdominal pelvic ultrasound and/or pelvic Magnetic Resonance Imaging are safe, accurate and non-invasive means of determining the size and configuration of the internal female genitalia. The assessment of uterine size and volume is helpful in the assessment of many conditions including disorders of sex development, precocious or delayed puberty, infertility and menstrual disorders. Using our own data from the assessment of MRI scans in healthy young females and data extracted from four studies that assessed uterine volume using transabdominal ultrasound in healthy females we have derived and validated a normative model of uterine volume from birth to age 40 years. This shows that uterine volume increases across childhood, with a faster increase in adolescence reflecting the influence of puberty, followed by a slow but progressive rise during adult life. The model suggests that around 84% of the variation in uterine volumes in the healthy population up to age 40 is due to age alone. The derivation of a validated normative model for uterine volume from birth to age 40 years has important clinical applications by providing age-related reference values for uterine volume.
- Can Coenzyme Q10 supplementation protect the ovarian reserve against oxidative damage? [JOURNAL ARTICLE]
- J Assist Reprod Genet 2016 Jun 3.
We investigated antioxidant effects of CoQ10 supplementation on the prevention of OS-induced ovarian damage and to evaluate the protective effect of such supplementation against OS-related DNA damage.Twenty-four adult female Sprague-Dawley rats were randomly divided into three groups (8 rats per group): group 1 (control): saline, ip, and orally; group 2 (cisplatin group): cisplatin, 4.5 mg/kg ip, two times with an interval of 7 days; and group 3 (cisplatin + CoQ10 group): cisplatin, 4.5 mg/kg ip, two times with an interval of 7 days, and 24 h before cisplatin, 150 mg/kg/day orally in 1 mL of saline daily for 14 days. Serum concentrations of anti-Mullerian hormone (AMH), number of AMH-positive follicles, the assessment of the intensity of 8'OHdG immunoreactivity, the primordial, antral and atretic follicle counts in the ovary were assessed.The mean serum AMH concentrations were 1.3 ± 0.19, 0.16 ± 0.03, and 0.27 ± 0.20 ng/mL in groups 1, 2, and 3, respectively (p < 0.01). Serum AMH levels were significantly higher in group 1 compared to groups 2 and 3 (p < 0.01 and p = 0.01, respectively). There was a statistically significant difference in AMH-positive follicle count between the groups (p < 0.01). Group 1 showed higher numbers of AMH-positive granulosa cells compared to group 2 (p = 0.01). A significant difference was found in the primordial, the atretic, and antral follicle counts between the three groups (p < 0.01, p < 0.01, and p < 0.01, respectively). The atretic follicle count was significantly lower in the cisplatin plus CoQ10 group compared to the cisplatin group (p < 0.01). The antral follicle counts were significantly higher in the cisplatin plus CoQ10 group compared with the cisplatin group (p < 0.01). There was a statistically significant difference in the intensity of staining of the follicles that were positive for anti-8'OHdG between the groups (p = 0.02). Group 1 showed a significant lower intensity of staining of the follicles positive for anti-8'OHdG compared with group 2 (p = 0.03).CoQ10 supplementation may protect ovarian reserve by counteracting both mitochondrial ovarian ageing and physiological programmed ovarian ageing although the certain effect of OS in female infertility is not clearly known.
- Extracellular vesicles in blood, milk and body fluids of the female and male urogenital tract and with special regard to reproduction. [JOURNAL ARTICLE]
- Crit Rev Clin Lab Sci 2016 Jul 23.:1-17.
Extracellular vesicles (EVs) are released from almost all cells and tissues. They are able to transport substances (e.g. proteins, RNA or DNA) at higher concentrations than in their environment and may adhere in a receptor-controlled manner to specific cells or tissues in order to release their content into the respective target structure. Blood contains high concentrations of EVs mainly derived from platelets, and, at a smaller amount, from erythrocytes. The female and male reproductive tracts produce EVs which may be associated with fertility or infertility and are released into body fluids and mucosas of the urogenital organs. In this review, the currently relevant detection methods are presented and critically compared. During pregnancy, placenta-derived EVs are dynamically detectable in peripheral blood with changing profiles depending upon progress of pregnancy and different pregnancy-associated pathologies, such as preeclampsia. EVs offer novel non-invasive diagnostic tools which may reflect the situation of the placenta and the foetus. EVs in urine have the potential of reflecting urogenital diseases including cancers of the neighbouring organs. Several methods for detection, quantification and phenotyping of EVs have been established, which include electron microscopy, flow cytometry, ELISA-like methods, Western blotting and analyses based on Brownian motion. This review article summarises the current knowledge about EVs in blood and cord blood, in the different compartments of the male and female reproductive tracts, in trophoblast cells from normal and pre-eclamptic pregnancies, in placenta ex vivo perfusate, in the amniotic fluid, and in breast milk, as well as their potential effects on natural killer cells as possible targets.
- Birth Weight by Gestational Age for 76,710 Twins Born in the United States as a Result of In Vitro Fertilization: 2006 to 2010. [JOURNAL ARTICLE]
- Am J Perinatol 2016 May 16.
Objective The objective of this study was to establish twin-specific birth weight percentiles by gestational age using U.S. twin births resulting from in vitro fertilization (IVF). Study Design A retrospective analysis of birth weight by completed weeks of gestation for 76,710 twin IVF births reported to the Society for Assisted Reproductive Technologies from 2006 to 2010. Mean and median birth weights and 3rd, 5th, 10th, 25th, 50th, 75th, 90th, and 97th percentiles were calculated by completed week of gestation and infant sex. Results IVF twin birth weight accelerates until term and then declines. The deceleration in twin birth weight occurs at 39 completed weeks of gestation for larger twins, those at or above the 50th percentile in weight. For smaller twins, the growth deceleration occurs earlier, at 38 weeks of gestation. IVF female and male twin birth weights for gestational age were similar to all IVF twins, showing similar decelerations near term. Conclusion Using U.S. IVF twin-specific growth charts, with known date of conception, twins demonstrate a deceleration in birth weight near term. Larger twins demonstrate a deceleration in birth weight by 39 completed weeks of gestation; smaller twins show a deceleration at 38 weeks. These data may assist in the clinical management of twins near term.
- An Important Role of Pumilio 1 in Regulating the Development of the Mammalian Female Germline. [Journal Article]
- Biol Reprod 2016 Jun; 94(6):134.
Pumilio/FBF (PUF) proteins are a highly conserved family of translational regulators. The Drosophila PUF protein, Pumilio, is crucial for germline establishment and fertility. In mammals, primordial folliculogenesis is a key process that establishes the initial cohort of female mammalian germ cells prior to birth, and this primordial follicle pool is a prerequisite for female reproductive competence. We sought to understand whether PUF proteins have a conserved role in mammals during primordial folliculogenesis and female reproductive competency. In mammals, two homologs of Pumilio exist: Pumilio 1 (Pum1) and Pum2. Here, we report that PUMILIO (PUM) 1 plays an important role in the establishment of the primordial follicle pool, meiosis, and female reproductive competency, whereas PUM2 does not have a detectable function in these processes. Furthermore, we show that PUM1 facilitates the transition of the late meiotic prophase I oocyte from pachytene to diplotene stage by regulating SYCP1 protein. Our study reveals an important role of translational regulation in mammalian female germ cell development.