Infertility female [keywords]
- Irinotecan metabolite SN38 results in germ cell loss in the testis but not in the ovary of prepubertal mice. [JOURNAL ARTICLE]
- Mol Hum Reprod 2016 Jul 28.
Does the Irinotecan metabolite 7-ethyl-10-hydroxycamptothecan (SN38) damage the gonads of male and female prepubertal mice?The Irinotecan metabolite SN38 reduces germ cell numbers within the seminiferous tubules of mouse testes at concentrations that are relevant to cancer patients, while in contrast it has little if any effect on the female germ cell population.Little is known about the role of the chemotherapeutic agent Irinotecan on female fertility, with only one article to date reporting menopausal symptoms in perimenopausal women treated with Irinotecan, while no data are available either on adult male fertility or on the impact of Irinotecan on the subsequent fertility of prepubertal cancer patients, female or male.Male and female gonads were obtained from postnatal day 5 C57BL/6 mice and exposed in vitro to a range of concentrations of the Irinotecan metabolite SN38: 0.002, 0.01, 0.05, 0.1 or 1 µg ml-1 for the testis and 0.1, 1, 2.5 or 5 µg ml-1 for the ovary, with treated gonads compared to control gonads not exposed to SN38: SN38 was dissolved in 0.5% dimethyl sulfoxide, with controls exposed to the same concentration of diluent. The number of testis fragments used for each analysis ranged between 3 and 9 per treatment group, while the number of ovaries used for each analysis ranged between 4 and 12 per treatment group.Neonatal mouse gonads were developed in vitro, with tissue analysed at the end of the 4-6 day culture period, following immunofluorescence or hematoxylin and eosin staining. Statistical analyses were performed using one-way ANOVA followed by Bonferroni post-hoc test for normally distributed data and Kruskal-Wallis test followed by Dunns post-test for non-parametric data.Abnormal testis morphology was observed when tissues were exposed to SN38, with a smaller seminiferous tubule diameter at the highest concentration of SN38 (1 µg ml(-1), p < 0.001 versus control) and increased number of Sertoli cell-only tubules at the two highest concentrations of SN38 (0.1 µg ml(-1), p < 0.001; (1) µg ml(-1), p < 0.0001, both versus control). Within seminiferous tubules, a dose response decrease was observed in both germ cell number (determined by the number of mouse vasa homologue (MVH)-positive cells) and in proliferating cell number (determined by the number of bromodeoxyuridine (BrdU)-positive cells), with significance reached at the two highest concentrations of SN38 (0.1 µg ml(-1), p < 0.01 for both; 1 µg ml(-1), p < 0.001-MVH, p < 0.01-BrdU; all versus control). No change was seen in protein expression of the apoptotic marker cleaved caspase 3. Double immunofluorescence showed that occasional proliferating germ cells were present in treated testes, even after exposure to the highest drug concentration. When prepubertal ovaries were treated with SN38, no effect was seen on germ cell number, apoptosis, or cell proliferation, even after exposure to the highest drug concentrations.As with any study using in vitro experiments with an experimental animal model, caution is required when extrapolating the present findings to humans. Differences between human and mouse spermatogonial development also need to be considered when assessing the effect of chemotherapeutic exposure. However, the prepubertal testes and ovaries used in the present studies contain germ cell populations that are representative of those found in prepubertal patients, and experimental tissues were exposed to drug concentrations within the range found in patient plasma.Our findings demonstrate that the prepubertal mouse ovary is relatively insensitive to exposure to the Irinotecan metabolite SN38, while it induces a marked dose-dependent sensitivity in the testicular germ cell population. The study identifies the importance of further investigation to identify the risk of infertility in young male cancer patients treated with Irinotecan. LARGE SCALE DATA: n/a STUDY FUNDING AND COMPETING INTERESTS: Work supported by Medical Research Grant (MRC) grant G1002118 and Children with Cancer UK grant 15-198. The authors declare that there is no conflict of interest that could prejudice the impartiality of the present research.
- Proteomic Analysis of Pachytene Spermatocytes of Sterile Hybrid Male Mice. [JOURNAL ARTICLE]
- Biol Reprod 2016 Jul 27.
Incompatibilities in interspecific hybrids, such as reduced hybrid fertility and lethality, are common features resulting from reproductive isolation that lead to speciation. Subspecies crosses of house mice produce offspring in which one sex is infertile or absent, yet the molecular mechanisms of hybrid sterility are poorly understood. In this study, we observed extensive asynapsis of chromosomes and disturbance of the sex body in pachytene spermatocytes of sterile F1 males (PWK/Ph female × C57BL/6J male). We report the high-confidence identification of 4,005 proteins in the pachytene spermatocytes of fertile F1 males (PWK/Ph male × C57BL/6J female) and sterile F1 males (PWK/Ph female × C57BL/6J male), of which 215 were upregulated and 381 were downregulated. Bioinformatics analysis of the proteome led to the identification of 43 and 59 proteins known to be essential for male meiosis and spermatogenesis in mice, respectively. Characterization of the proteome of pachytene spermatocytes associated with hybrid male sterility provides an inventory of proteins that is useful for understanding meiosis and the mechanisms of hybrid male infertility.
- Female circumcision in Nigeria and attitudes towards its discontinuation. [Journal Article]
- Afr J Med Med Sci 2015 Dec; 44(4):343-54.
Female Circumcision (FC) is a harmful traditional practice and remains a public health problem particularly in the era of HIV/AIDS. Aside its numerous health implications, it can cause infertility, complications in childbirth and increased risk of newborn deaths. FC is widely practised in Nigeria.The study assessed the level of FC, daughters' circumcision and attitude towards discontinuation of the practice among women of reproductive age.Data were extracted from the 2008 Nigeria Demographic Health and Survey. Data were analysed using Chi-square and binary logistic regression models (á = 0.05).Among the respondents, prevalence of FC was 49.2% with 30.6% having circumcised their daughters and 25.8% wishing the practice to continue. About 56% of circumcised women also circumcised their daughters whereas only 2.9% of uncircumcised women circumcised their daughters. Approximately 69.8% of women who had circumcised their daughters would like FC to continue compared to 8.8% of those who never circumcised any of their daughters. The likelihood of FC was higher (OR = 2.07; C.I = 1.85-2.30) among Moslems compare to Christians. Igbo women were less likely to discontinue FC compared to women of Hausa/Fulani ethnic group despite controlling for the confounding variables (OR = 0.57; C.I = 0.35-0.91).Female circumcision is still practiced in all parts of Nigeria and a high proportion of women reported that the practice should continue. There is need to intensify efforts on the campaign against female circumcision in Nigeria.
- 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.
- [QUANTITATIVE DNA EVALUATION OF THE HIGH CARCINOGENIC RISK OF HUMAN PAPILLOMA VIRUSES AND HUMAN HERPES VIRUSES IN MALES WITH FERTILITY DISORDERS]. [English Abstract, Journal Article]
- Vopr Virusol 2016; 61(2):63-8.
Infertility is an actual medical and social problem. In 50% of couples it is associated with the male factor and in more than 50% of cases the etiology of the infertility remains insufficiently understood. The goal of this work was to study the prevalence and to perform quantitative analysis of the human herpes viruses (HHV) and high carcinogenic risk papilloma viruses (HR HPV) in males with infertility, as well as to assess the impact of these infections on sperm parameters. Ejaculate samples obtained from 196 males fall into 3 groups. Group 1 included men with the infertility of unknown etiology (n = 112); group 2, patients who had female partners with the history of spontaneous abortion (n = 63); group 3 (control), healthy men (n = 21). HHV and HR HPV DNA in the ejaculates were detected in a total of 42/196 (21.4%) males: in 31 and 11 patients in groups 1 and 2, respectively (p > 0.05) and in none of healthy males. HHV were detected in 24/42; HR HPV, in 18/42 males (p > 0.05) without significant difference between the groups. Among HR HPV genotypes of the clade A9 in ejaculate were more frequent (14/18, p = 0.04). Comparative analysis of the sperm parameters showed that in the ejaculates of the infected patients sperm motility as well as the number of morphologically normal cells were significantly reduced compared with the healthy men. The quantification of the viral DNA revealed that in 31% of the male ejaculates the viral load was high: > 3 Ig10/100000 cells.
Conclusion.The detection of HHV and HR HPV in the ejaculate is associated with male infertility. Quantification of the viral DNA in the ejaculate is a useful indicator for monitoring viral infections in infertility and for decision to start therapy.
- 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.
- Oocyte or embryo donation to women of advanced reproductive age: an Ethics Committee opinion. [JOURNAL ARTICLE]
- Fertil Steril 2016 Jul 20.
Advanced reproductive age (ARA) is a risk factor for female infertility, pregnancy loss, fetal anomalies, stillbirth, and obstetric complications. Oocyte donation reverses the age-related decline in implantation and birth rates of women in their 40s and 50s and restores pregnancy potential beyond menopause. However, obstetrical complications in older patients remain high particularly related to operative delivery, and hypertensive and cardiovascular risks. Physicians should perform a thorough medical evaluation designed to assess the physical fitness of a patient for pregnancy before deciding to attempt transfer of embryos to any woman of advanced reproductive age (>45 years). Embryo transfer should be strongly discouraged or denied to women of ARA with underlying conditions that increase or exacerbate obstetrical risks. Because of concerns related to the high-risk nature of pregnancy, as well as longevity, treatment of women over the age of 55 should be generally discouraged. This statement replaces the earlier ASRM Ethics Committee document of the same name, last published in 2013 (Fertil Steril 2013;100:337-40).
- Tips for safe laparoscopic multiple myomectomy. [JOURNAL ARTICLE]
- J Minim Invasive Gynecol 2016 Jul 19.
To demonstrate key steps in performing safe laparoscopic multiple myomectomy.Video focuses on step wise description of all the major steps of surgical technique.About one-third of women with fibroids present with symptoms that are severe enough to warrant treatment. We demonstrate a case of 27 year old female with complaints of secondary infertility and menorrhagia. On examination the uterus was enlarged up to 24 weeks size. Ultrasonography mapping located 7 myomas with a size range of 3 to 10 cms, belonging to FIGO class 2,3,4,5,6 and 7. Generally, laparotomy or laparoscopy and mini-laparotomy is performed for such cases of multiple myomas. However, total laparoscopic approach can confer benefits if performed following safe steps and within good time.Laparoscopic multiple myomectomy with morcellation in bag. Following were the key steps of surgery: 1. Higher port position using Lee Huang point for primary port. 2. Intermittent vasopressin use for each myomectomy. 3. Cold technique of myomectomy. 4. Myoma lace creation. 5. Multiple layer suturing using double ended barbed sutures. 6. Myoma garland creation. 7. Morcellation in a stomach shaped bag.Intermittent use of vasopressin is effective in reducing blood loss. Suturing using barbed sutures is less time consuming. Creating lace of myomas prevents losing them in abdominal cavity and creating garland of myomas helps in easier bagging. Morcellation in bag prevents dissemination of bits of myoma and visceral injury. These steps help in performing laparoscopic multiple myomectomy safely. However, technique should be reserved for selected cases and should be performed by surgical team having required expertise and experience.
- Steroidogenic enzymes of adipose tissue in modulation of trivalent chromium in a mouse model of PCOS. [JOURNAL ARTICLE]
- Gynecol Endocrinol 2016 Jul 22.:1-5.
Polycystic ovary syndrome (PCOS) is a type of endocrine metabolic disorder with many different consequences to health, most commonly infertility, obesity and insulin resistance. Trivalent chromium (Cr(3+)) was previously found to improve the metabolic profiles of patients with PCOS. The aim of this study was to explore the effect of Cr on regulating steroidogenic enzymes in adipose tissue. Female BALB/c mice were divided into three groups (n = 6 per group): the control group, PCOS + placebo milk group and PCOS + Cr-containing milk group. The dietary intake of Cr significantly decreased fasting blood sugar (FBS) and homeostasis model assessment of insulin resistance levels in the murine model of PCOS. Importantly, we found significant correlations among the levels of Cr, insulin and dehydroepiandrosterone (DHEA). In adipose tissue, decreases in the enzyme expressions of 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-hydroxysteroid dehydrogenase, but not of aromatase, were observed. By understanding the role of steroidogenic enzymes in PCOS in normal and pathological states, trace elements may be used as a form of adjunctive therapy in the management of patients with PCOS.
- Genome-Wide Association Mapping for Female Infertility in Inbred Mice. [JOURNAL ARTICLE]
- G3 (Bethesda) 2016 Jul 22.
The genetic factors underlying female infertility in humans are only partially understood. Here, we performed a genome-wide association study of female infertility in 25 inbred mouse strains by using publicly available SNP data. As a result, a total of 4 SNPs were identified after chromosome-wise multiple test correction. The first SNP rs29972765 is located in a gene desert on chromosome 18, about 72 kb upstream of Skor2 (SKI family transcriptional corepressor 2). The second SNP rs30415957 resides in the intron of Plce1 (phospholipase C epsilon 1). The remaining two SNPs (rs30768258 and rs31216810) are close to each other on chromosome 19 in vicinity of Sorbs1 (sorbin and SH3 domain containing 1). Using quantitative RT-PCR, we found that Sorbs1 is highly expressed in the mouse uterus during embryo implantation. Knockdown of Sorbs1 by siRNA attenuates the induction of differentiation marker gene Prl8a2 (decidual prolactin-related protein) in an in vitro model of decidualization using mouse endometrial stromal cells, suggesting that Sorbs1 may be a potential candidate gene for female infertility in mice. Our results may represent an opportunity to further understand female infertility in humans.