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Human infertility

Peng Wang, San-Pin Wu, Kelsey E Brooks, Andrew M Kelleher, Jessica Milano-Foster, Francesco J DeMayo, Thomas E Spencer
Forkhead box A2 (FOXA2) is a pioneer transcription factor involved in organ development, function and cancer. In the uterus, FOXA2 is essential for pregnancy and expressed specifically in the glands of the endometrium loss of FOXA2 function occurs during development of endometrial cancer in humans. The present study describes the development of a mouse model for conditional expression of mouse FOXA2. Using a system consisting of a minigene located at the Rosa26 locus, a CAG-S-mFOXA2 allele was generated in embryonic stem cells and subsequently in mice; before activation, the minigene is silent due to a floxed stop cassette inserted between the promoter and the transgene...
March 13, 2018: Endocrinology
Harriet C Fitzgerald, Jemma Evans, Nicholas Johnson, Giuseppe Infusini, Andrew Webb, Luk J R Rombauts, Beverley J Vollenhoven, Lois A Salamonsen, Tracey A Edgell
The regenerative, proliferative phase of a woman's menstrual cycle is a critical period which lays the foundation for the subsequent, receptive secretory phase. Although endometrial glands and their secretions are essential for embryo implantation and survival, the proliferative phase, when these glands form, has been rarely examined. We hypothesized that alterations in the secreted proteome of the endometrium of idiopathic infertile women would reflect a disturbance in proliferative phase endometrial regeneration...
March 13, 2018: Biology of Reproduction
Jessica L H Walters, Geoffry N De Iuliis, Matthew D Dun, Robert John Aitken, Eileen A McLaughlin, Brett Nixon, Elizabeth G Bromfield
One of the leading causes of male infertility is defective sperm function, a pathology that commonly arises from oxidative stress in the germline. Lipid peroxidation events in the sperm plasma membrane result in the generation of cytotoxic aldehydes such as 4-hydroxynonenal (4HNE), which accentuate the production of reactive oxygen species (ROS) and cause cellular damage. One of the key enzymes involved in the metabolism of polyunsaturated fatty acids to 4HNE in somatic cells is arachidonate 15-lipoxygenase (ALOX15)...
March 13, 2018: Biology of Reproduction
Sabrina Z Jan, Aldo Jongejan, Cindy M Korver, Saskia K M van Daalen, Ans M M van Pelt, Sjoerd Repping, Geert Hamer
To prevent chromosomal aberrations to be transmitted to the offspring, strict meiotic checkpoints are in place to remove aberrant spermatocytes. However, in about 1% of all males these checkpoints cause complete meiotic arrest leading to azoospermia and subsequent infertility. We here unravel two clearly distinct meiotic arrest mechanisms that act during the prophase of human male meiosis. Type I arrested spermatocytes display severe asynapsis of the homologous chromosomes, disturbed XY-body formation and increased expression of the Y-chromosome encoded gene ZFY and seem to activate a DNA damage pathway leading to induction of p63, possibly causing spermatocyte apoptosis...
March 14, 2018: Development
Kelly A Campen, Katherine M Kucharczyk, Benjamin Bogin, Julie M Ehrlich, Catherine M H Combelles
STUDY QUESTION: What are the effects of exposure to bisphenol A (BPA) or bisphenol S (BPS) during IVM on bovine oocyte maturation, spindle morphology and chromosome alignment? SUMMARY ANSWER: Exposure to BPA or BPS during IVM resulted in increased spindle abnormalities and chromosome misalignment, even at very low concentrations. WHAT IS KNOWN ALREADY: BPA is an endocrine disrupting chemical that alters oocyte maturation, spindle morphology and chromosome alignment in a range of species...
March 12, 2018: Human Reproduction
Xiaowei Wen, Jun Xie, Lixia Zhou, Yong Fan, Baofeng Yu, Qiuju Chen, Yonglun Fu, Zheng Yan, Haiyan Guo, Qifeng Lyu, Yanping Kuang, Weiran Chai
Medroxyprogesterone 17-acetate (MPA) combined with human menopausal gonadotropin (hMG) has been effectively used for ovarian stimulation in clinical practice. However, the molecular mechanism of MPA + hMG treatment in follicular development is poorly described. Here we performed a study to investigate the impact of MPA + hMG on ovarian stimulation utilizing a mouse model in vivo. Forty female BALB/C mice were randomly divided into four groups of 10 each and treated during ciestrus stage and continued for 5 days: control group, MPA group, hMG group, and MPA + hMG group...
March 13, 2018: Scientific Reports
Xiao Wang, Huarong Wang, Wei Liu, Zhiyuan Zhang, Yanhao Zhang, Wenqiang Zhang, Zijiang Chen, Guoliang Xia, Chao Wang
Polycystic ovary syndrome (PCOS), which is characterized by hyperandrogenism, is a complex endocrinopathy that affects the fertility of 9%-18% of reproductive-age women. However, the exact mechanism of PCOS, especially hyperandrogen-induced anovulation, is largely unknown to date. Physiologically, the natriuretic peptide type C/natriuretic peptide receptor 2 (CNP/NPR2) system is essential for sustaining oocyte meiotic arrest until the preovulatory luteinizing hormone (LH) surge. We therefore hypothesized that the CNP/NPR2 system is also involved in PCOS and contributes to arresting oocyte meiosis and ovulation...
March 13, 2018: Clinical Science (1979-)
Miranda Håkansson, Monica Oguttu, Kristina Gemzell-Danielsson, Marlene Makenzius
Introduction: Adolescent pregnancy represents a serious public health issue in sub-Saharan Africa, and stigmatising attitudes are contributing factors. This study investigates stigmatising attitudes related to adolescent pregnancy, abortion and contraceptive use among healthcare providers working with postabortion care (PAC) in a low-resource setting in Kenya. Methods: A mixed methods approach in a convergent design was utilised to capture attitudes related to abortion and contraceptive use among 86 (f=62; m=19) PAC providers in Kisumu, Kenya...
2018: BMJ Global Health
Erica Silvestris, Giovanni de Pergola, Raffaele Rosania, Giuseppe Loverro
Both obesity and overweight are increasing worldwide and have detrimental influences on several human body functions including the reproductive health. In particular, obese women undergo perturbations of the 'hypothalamic pituitary ovarian axis', and frequently suffer of menstrual dysfunction leading to anovulation and infertility. Besides the hormone disorders and subfertility that are common in the polycystic ovary syndrome (PCOS), in obesity the adipocytes act as endocrine organ. The adipose tissue indeed, releases a number of bioactive molecules, namely adipokines, that variably interact with multiple molecular pathways of insulin resistance, inflammation, hypertension, cardiovascular risk, coagulation, and oocyte differentiation and maturation...
March 9, 2018: Reproductive Biology and Endocrinology: RB&E
Zine-Eddine Kherraf, Beatrice Conne, Amir Amiri-Yekta, Marie Christou Kent, Charles Coutton, Jessica Escoffier, Serge Nef, Christophe Arnoult, Pierre F Ray
High throughput sequencing (HTS) and CRISPR/Cas9 are two recent technologies that are currently revolutionizing biological and clinical research. Both techniques are complementary as HTS permits to identify new genetic variants and genes involved in various pathologies and CRISPR/Cas9 permits to create animals or cell models to validate the effect of the identified variants, to characterize the pathogeny of the identified variants and the function of the genes of interest and ultimately to provide ways of correcting the molecular defects...
March 6, 2018: Molecular and Cellular Endocrinology
Mili Nailwal, Jenabhai B Chauhan
BACKGROUND: DEAD-box helicase 3, Y-linked (DBY) is a candidate gene of the AZF region which is involved in spermatogenesis process. Mutations in the DBY gene may disrupt the spermatogenesis and lead to infertility in men. Identification of functionally neutral mutation from the disease-causing mutation is the biggest challenge in human genetic variation analysis. Owing to the importance of DBY in male infertility, functional analysis was carried out to reveal the association between genetic mutation and phenotypic variation through various in silico approaches...
March 8, 2018: Interdisciplinary Sciences, Computational Life Sciences
Chithra Janardhanan Susheelamma, Sathy M Pillai, Sivakumari Asha Nair
Oestrogen-progesterone signalling is highly versatile and critical for the maintenance of healthy endometrium in humans. The genomic and nongenomic signalling cascades initiated by these hormones in differentiated cells of endometrium have been the primary focus of research since 1920s. However, last decade of research has shown a significant role of stem cells in the maintenance of a healthy endometrium and the modulatory effects of hormones on these cells. Endometriosis, the growth of endometrium outside the uterus, is very common in infertile patients and the elusiveness in understanding of disease pathology causes hindrance in selection of treatment approaches to enhance fertility...
March 8, 2018: Expert Reviews in Molecular Medicine
R Mändar, S Türk, P Korrovits, K Ausmees, M Punab
Micro-organisms are tightly integrated into host-microbiota ecosystem. Microbiota of human semen has been studied so far mostly in case of infertility or prostatitis. We aimed to reveal possible impact of sexual debut on seminal microbiota in healthy young men. The study group included 68 young healthy men, of them 12 men without sexual experience, 11 men with single lifetime sexual partner and 45 men with multiple lifetime sexual partners. Basic semen parameters were similar for all subgroups, and no correlation between sexual experience and WBC counts in semen was found...
March 7, 2018: Andrology
S Keihani, C Martin, J R Craig, C Zhang, A P Presson, J B Myers, K I Aston, B R Emery, D T Carrell, J M Hotaling
The effects of statin use on conventional semen parameters in humans are largely unknown and have not been previously studied in subfertile men. We retrospectively reviewed data from 10,140 patients seen at our fertility clinic between 2002 and 2013 to assess the effects of statin use on semen parameters. Men who used any statins for >3 months before semen sample collection were included as cases. Data were gathered on patient age, medication use and conventional semen parameters. A total of 118 patients (126 samples) used statins for at least 3 months before semen sample collection...
March 7, 2018: Andrologia
Ágnes Molnár, Attila Patócs, István Likó, Gábor Nyírő, Károly Rácz, Miklós Tóth, Beatrix Sármán
BACKGROUND: Glucocorticoid resistance is a rare, sporadic or familial condition caused by mutation of the gene encoding the glucocorticoid receptor (GR). Clinically it is characterized by symptoms developed due to local, tissue-specific, or generalized partial insensitivity to glucocorticoids. CASE PRESENTATION: A 31-year-old woman was evaluated because of infertility at the Endocrine Unit of the 2nd Department of Medicine, Semmelweis University. During her laboratory investigations, elevated serum and salivary cortisol were observed which failed to be suppressed after administration of 1 mg dexamethasone...
March 6, 2018: BMC Medical Genetics
Erkan Gumus, Ismail Sari, Meral Yilmaz, Ali Cetin
Improving the success of in vitro fertilization (IVF) and infertility treatment depend on understanding basic cellular and molecular mechanisms of human preimplantation development. Pre-implantation mouse embryo model is an ideal empiric system to understand these mechanisms. This study was aimed to investigate the gene and protein expressions of LAMTOR1 in mouse oocytes and pre-implantation embryos at different developmental stages. The findings demonstrate that LAMTOR1 was detected in the oocytes and in subsequent all stages of embryo development...
March 3, 2018: Gene Expression Patterns: GEP
Jianqiang Yang, Ning Yi, Junhui Zhang, Wen He, Di He, Wanwan Wu, Shuyang Xu, Feng Li, Guoping Fan, Xianmin Zhu, Zhigang Xue, Wensheng Zhou
Thyroid stimulating hormone receptor (TSHR), a G-protein-coupled receptor, is important for thyroid development and growth. In several cases, frameshift and/or nonsense mutations in TSHR were found in the patients with congenital hypothyroidism (CH), however they have not been functionally studied in an animal model. In the present work, we generated a unique TshrDf/Df rat model that recapitulates the phenotypes in TSHR Y444X patient by CRISPR/Cas genome editing technology. In this rat model, TSHR is truncated at the second transmembrane domain, leading to CH phenotypes as what was observed in the patients, including dwarf, thyroid aplasia, infertility, TSH resistant as well as low serum thyroid hormone levels...
March 5, 2018: Scientific Reports
Necip Pirincci, Serkan Yıldırım, Abuzer Tas, Yagmur Kuscu, Tunc Ozan, Fatih Firdolas, Halit Demir, Ahmet Karakeci
OBJECTIVES: Prolidase plays a vital role in collagen turnover, matrix remodeling and cell growth. We aimed to evaluate the association between treatment with chorionic gonadotropin and infertility and erectile dysfunction, by investigating tissue prolidase activity, oxidative stress and levels of antioxidant enzymes. MATERIALS AND METHODS: Sixteen (16) male Wistar albino rats used in this study were randomly divided into two groups: rats treated with human chorionic gonadotropin (hCG) and control rats (n = 8 in each group)...
March 5, 2018: Medical Principles and Practice: International Journal of the Kuwait University, Health Science Centre
Jiaqi Li, Jianwei Li, Shu Jiang, Ruichao Yu, Yerong Yu
RATIONALE: Thyrotropin-secreting adenoma (TSHoma) is rare, diagnosis and treatment are often delayed if the condition coexists with Hashimoto thyroiditis. The enlarged pituitary adenoma may eventually induce panhypopituitarism, infertility, or the compression of optic nerves and optic chiasma. PATIENT CONCERNS: This patient was a 36-year-old man who had been referred to the pituitary disease multidisciplinary team (MDT) of the West China Hospital, due to infertility...
January 2018: Medicine (Baltimore)
Gamze Sinem Çağlar, Nicolas Garrido
Human papilloma virus (HPV) is one of the most common viral sexually-transmitted diseases worldwide. The prevalence of HPV is higher in infertile males when compared with fertile men and ranges between 10 and 35.7% in men affected by unexplained infertility. HPV can bind to spermatozoa and can potentially be transferred to fertilized oocytes. Viral detection in blastocysts and trophoblastic cells is associated with impaired embryo development and poor pregnancy outcomes. Nevertheless, attempts to eliminate HPV-DNA from sperm samples through routine washing techniques have failed...
March 1, 2018: Journal of the Turkish German Gynecological Association
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