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Molecular Human Reproduction

Robert John Aitken
This article is a personal perspective on male infertility, a condition that is not only extremely prevalent but also a major reason for couples to resort to assisted reproductive technology. The introduction of intra-cytoplasmic sperm injection (ICSI) as a form of facilitated fertilization had a revolutionary impact on our capacity to treat cases of male infertility associated with severely-compromised semen quality. However, the widespread use of this technique is also thought to pose risks in terms of the incidence of miscarriage, the health and wellbeing of the offspring and perpetuation of the infertile phenotype into future generations...
March 13, 2018: Molecular Human Reproduction
F de Michele, J Poels, M G Giudice, F De Smedt, J Ambroise, M Vermeulen, D Gruson, C Wyns
STUDY QUESTION: How does the formation of the blood-testis barrier (BTB), as reflected by the expression of connexin 43 and claudin 11 proteins during the pubertal transition period, take place in vitro compared to samples from a large cohort of pre/peripubertal boys? SUMMARY ANSWER: The BTB connexin 43 and claudin 11 expression patterns appeared to be partially achieved in organotypic culture when compared to that in samples from 71 pre/peripubertal patients. WHAT IS KNOWN ALREADY: Although alterations in the protein expression patterns of the BTB, whose main components are connexin 43 and claudin 11, are known to be associated with impaired spermatogenesis in mice and adult men, there is a lack of knowledge on its formation in pre-peripubertal human tissue both in vitro and in vivo...
March 12, 2018: Molecular Human Reproduction
Z Merhi, E Buyuk, M J Cipolla
STUDY QUESTION: Does vitamin D attenuate the adverse effects of advanced glycation end products (AGEs) on steroidogenesis by human granulosa cells (GCs)? SUMMARY ANSWER: AGEs alter the expression of genes important in steroidogenesis while 1,25-dihydroxyvitamin D3 (vit D3) in vitro attenuates some of the actions of AGEs on steroidogenic gene expression, possibly by downregulating the expression of the pro-inflammatory cell membrane receptor for AGEs (RAGE). WHAT IS KNOWN ALREADY: Vitamin D attenuates the pro-inflammatory effects of AGEs in non-ovarian tissues...
March 12, 2018: Molecular Human Reproduction
Sabrina L Roberti, Romina Higa, Verónica White, Theresa L Powell, Thomas Jansson, Alicia Jawerbaum
STUDY QUESTION: What are the consequences of inhibiting mTOR, the mechanistic target of rapamycin, and the peroxisome proliferator activated receptor gamma (PPARγ) and PPARδ pathways in the early post-implantation period on decidual function, embryo viability and feto-placental growth in the rat? SUMMARY ANSWER: mTOR inhibition from day 7 to day 9 of pregnancy in rats caused decidual PPARγ and PPARδ upregulation on day 9 of pregnancy and resulted in embryo resorption by day 14 of pregnancy...
March 12, 2018: Molecular Human Reproduction
C L Depoix, F Haegemann, F Debiève, C Hubinont
STUDY QUESTION: Is 8% O2 a better percentage of atmospheric oxygen for long-term cultures of human primary term cytotrophoblasts than the conventional 21% O2 traditionally used in cell culture? SUMMARY ANSWER: Human primary term cytotrophoblasts are able to differentiate into syncytiotrophoblasts under both atmospheric oxygen levels. WHAT IS KNOWN ALREADY: Cell culture is traditionally done under 21% O2, which is equal to a pO2 of ~160 mm Hg...
March 9, 2018: Molecular Human Reproduction
Maria Gomes Fernandes, Monika Bialecka, Daniela C F Salvatori, Susana M Chuva de Sousa Lopes
STUDY QUESTION: Which set of antibodies can be used to identify migratory and early post-migratory human primordial germ cells (hPGCs)? STUDY FINDING: We validated the specificity of 33 antibodies for 31 markers, including POU5F1, NANOG, PRDM1 and TFAP2C as specific markers of hPGCs at 4.5 weeks of development of Carnegie stage (CS12-13), whereas KIT and SOX17 also marked the intra-aortic hematopoietic stem cell cluster in the aorta-gonad-mesonephros (AGM). WHAT IS KNOWN ALREADY: The dynamics of gene expression during germ cell development in mice is well characterized and this knowledge has proved crucial to allow the development of protocols for the in-vitro derivation of functional gametes...
March 8, 2018: Molecular Human Reproduction
S García-Martínez, M A Sánchez-Hurtado, H Gutiérrez, F M Sánchez-Margallo, R Romar, R Latorre, P Coy, O López-Albors
STUDY QUESTION: Is O2 tension in the pig oviduct and uterus affected by the estrous cycle stage and the animal's age, and can the outcome of in vitro embryo development be improved by mimicking these physiological values? SUMMARY ANSWER: O2 tension within the pig reproductive organs is affected by the animal's age, and values close to those measured in vivo have a positive impact on embryo development and quality when used during IVF and embryo culture (EC). WHAT IS KNOWN ALREADY: To obtain a healthy embryo in vitro, it is necessary to adopt a culture microenvironment that approximates physiological conditions...
February 27, 2018: Molecular Human Reproduction
S Mishra, E Kacin, P Stamatiadis, S Franck, M Van der Jeught, H Mertes, G Pennings, P De Sutter, K Sermon, B Heindryckx, M Geens
The derivation of gametes from patient-specific pluripotent stem cells may provide new perspectives for genetic parenthood for patients currently facing sterility. We use current data to assess the gamete differentiation potential of patient-specific pluripotent stem cells and to determine which reprogramming strategy holds the greatest promise for future clinical applications. First, we compare the two best established somatic cell reprogramming strategies: the production of induced pluripotent stem cells (iPSC) and somatic cell nuclear transfer followed by embryonic stem cell derivation (SCNT-ESC)...
February 19, 2018: Molecular Human Reproduction
F Horicks, G Van Den Steen, C Gervy, H J Clarke, I Demeestere
STUDY QUESTION: Does fertility preservation using gonadotrophin-releasing hormone (GnRH) analogues during chemotherapy act through a direct effect on the ovary or through inhibition of FSH secretion? SUMMARY ANSWER: The absence of FSH in vivo and the direct exposition of ovarian follicles to GnRH analogues in vitro did not prevent chemotherapy-induced ovarian damage. WHAT IS KNOWN ALREADY: The potential mechanisms of action of GnRH analogues in protecting ovaries against chemotherapy damage remain poorly understood...
February 9, 2018: Molecular Human Reproduction
M C Lardone, F Argandoña, M Lorca, A Piottante, M Flórez, C Palma, M Ebensperger, A Castro
STUDY QUESTION: Is the expression of steroidogenic enzyme 17α-Hydroxylase/17,20-Lyase (CYP17A1) downregulated in Leydig cells (LCs) of men with spermatogenic failure and compensated impairment of LC function i.e. a low testosterone to LH (T/LH) ratio? SUMMARY ANSWER: Although the transcriptional expression of CYP17A1 is increased, its protein expression is decreased, in isolated LCs of men with spermatogenic failure and reduced serum T/LH. WHAT IS KNOWN ALREADY: Primary spermatogenic defects have been associated with functional and morphological abnormalities of LCs, characterized by decreased serum testosterone (T) levels, decreased T/LH, increased 17β-estradiol (E2) and E2/T ratio, and larger clusters of LCs (LC hyperplasia)...
February 9, 2018: Molecular Human Reproduction
Shun Bai, Le Cheng, Yingwen Zhang, Chunsen Zhu, Zhiping Zhu, Ruping Zhu, C Yan Cheng, Lan Ye, Ke Zheng
STUDY QUESTION: What is the physiological role of Rictor in spermatogenic cells? SUMMARY ANSWER: Germline expression of Rictor regulates spermatogonial differentiation and has an essential role in coordinating germ cells and Sertoli cells in maintaining intact cell-cell adhesion dynamics and cytoskeleton-based architecture in the seminiferous epithelium. WHAT IS KNOWN ALREADY: The mechanistic target of rapamycin (mTOR) resides in its functions as the catalytic subunits of the structurally and functionally distinct mTORC1 and mTORC2 complexes...
February 6, 2018: Molecular Human Reproduction
Joep Geraedts
Recently, American colleagues called for a systematic collection of anonymized data on how many embryos and foetuses are deselected per institution per year, and for which conditions. These authors argued that if this information would be reported to a government agency or international body, the information would provide a baseline against which jurisdiction-specific trends in selection could be assessed. People who have disabilities, together with other key stakeholders, laypeople and experts, would then be in a position, to assess the social impact of human selecting technologies and to make recommendations for action to mitigate negative effects as appropriate...
February 2, 2018: Molecular Human Reproduction
M McLaughlin, D F Albertini, W H B Wallace, R A Anderson, E E Telfer
STUDY QUESTION: Can complete oocyte development be achieved from human ovarian tissue containing primordial/unilaminar follicles and grown in vitro in a multi-step culture to meiotic maturation demonstrated by the formation of polar bodies and a Metaphase II spindle? SUMMARY ANSWER: Development of human oocytes from primordial/unilaminar stages to resumption of meiosis (Metaphase II) and emission of a polar body was achieved within a serum free multi-step culture system...
January 30, 2018: Molecular Human Reproduction
Pradeepthi Bathala, Zeinab Fereshteh, Kun Li, Amal A Al-Dossary, Deni S Galileo, Patricia A Martin-DeLeon
STUDY QUESTIONS: Are extracellular vesicles (EVs) in the murine oviduct (oviductosomes, OVS) conserved in humans and do they play a role in the fertility of Pmca4-/-females? SUMMARY ANSWER: OVS and their fertility-modulating proteins are conserved in humans, arise via the apocrine pathway, and mediate a compensatory upregulation of PMCA1 (Plasma membrane Ca2+-ATPase 1) in Pmca4-/- female mice during proestrus/estrus, to account for their fertility. WHAT IS KNOWN ALREADY?: Recently murine OVS were identified and shown during proestrus/estrus to express elevated levels of PMCA4 which they can deliver to sperm...
January 23, 2018: Molecular Human Reproduction
Jinghua Hu, D Jo Merriner, Anne E O'Connor, Brendan J Houston, Luc Furic, Mark P Hedger, Moira K O'Bryan
STUDY QUESTION: What is the role of epididymal cysteine-rich secretory proteins (CRISPs) in male fertility? SUMMARY ANSWER: While epididymal CRISPs are not absolutely required for male fertility, they are required for optimal sperm function. WHAT IS KNOWN ALREADY: CRISPs are members of the CRISP, Antigen 5 and Pathogenesis related protein 1 (CAP) superfamily and are characterised by the presence of an N-terminal CAP domain and a C-terminal CRISP domain...
January 18, 2018: Molecular Human Reproduction
Yin Zhao, YanFang Zheng, XiaoXia Liu, QingQing Luo, Di Wu, XiaoPing Liu, Li Zou
STUDY QUESTION: Is it possible to improve vascular remodeling by inhibiting the excessive expression of protease activated receptor 1 (PAR-1) in trophoblast of abnormal placenta? SUMMARY ANSWER: Inhibition of trophoblast PAR-1 overexpression may promote placental angiogenesis and vascular remodeling, offering an alternative therapeutic approach for preeclampsia. WHAT IS KNOWN ALREADY: PAR-1 is high-affinity receptor of thrombin. Thrombin increases sFlt-1 secretion in trophoblast via the activation of PAR-1...
January 9, 2018: Molecular Human Reproduction
Christopher L R Barratt
No abstract text is available yet for this article.
January 5, 2018: Molecular Human Reproduction
Kathrein von Kopylow, Wolfgang Schulze, Andrea Salzbrunn, Matthias Schaks, Elke Schäfer, Beate Roth, Stefan Schlatt, Andrej-Nikolai Spiess
STUDY QUESTION: Is it possible to induce in-vitro reorganization of primary human testis cells from testicular sperm extraction (TESE) biopsies, maintain their long-term cultivation in a 2D system and identify cellular compositions? SUMMARY ANSWER: In-vitro reorganization of primary human testis cells from TESE biopsies and their long-term cultivation on uncoated cell culture dishes is feasible and the cellular compositions can be uncovered through gene expression and microscopic analyses...
January 3, 2018: Molecular Human Reproduction
M Mincheva, R Sandhowe-Klaverkamp, J Wistuba, K Redmann, J-B Stukenborg, S Kliesch, S Schlatt
STUDY QUESTION: Can enzymatically dispersed testicular cells from adult men reassemble into seminiferous cord-like structures in vitro? SUMMARY ANSWER: Adult human testicular somatic cells reassembled into testicular cord-like structures via dynamic interactions of Sertoli and peritubular cells. WHAT IS KNOWN ALREADY: In vitro approaches using dispersed single cell suspensions of human testes to generate seminiferous tubule structures and to initiate their functionality have as yet shown only limited success...
December 26, 2017: Molecular Human Reproduction
Arturo Matamoros-Volante, Ayelen Moreno-Irusta, Paulina Torres-Rodriguez, Laura Giojalas, María G Gervasi, Pablo E Visconti, Claudia L Treviño
STUDY QUESTION: Is image-based flow cytometry a useful tool to study intracellular events in human sperm such as protein tyrosine phosphorylation or signaling processes? SUMMARY ANSWER: Image-based flow cytometry is a powerful tool to study intracellular events in a relevant number of sperm cells, which enables a robust statistical analysis providing spatial resolution in terms of the specific subcellular localization of the labeling. WHAT IS KNOWN ALREADY: Sperm capacitation is required for fertilization...
February 1, 2018: Molecular Human Reproduction
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