### A. Overview

Extracellular purines (adenosine, ADP, and ATP) and pyrimidines (UDP and UTP) are important signaling molecules that mediate diverse biological effects via cell-surface receptors termed purine receptors. In this review particular emphasis is placed on the discrepancy between the

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Receptors for Purines and Pyrimidines

BACKGROUND Semen quality is taken as a surrogate measure of male fecundity in clinical andrology, male fertility, reproductive toxicology, epidemiology and pregnancy risk assessments. Reference intervals for values of semen parameters from a fertile population could provide data from which prognosis of fertility or diagnosis of infertility can be extrapolated. METHODS Semen samples from over 4500 men in 14 countries on four continents were obtained from retrospective and prospective analyses on fertile men, men of unknown fertility status and men selected as normozoospermic. Men whose partners had a time-to-pregnancy (TTP) of < or =12 months were chosen as individuals to provide reference distributions for semen parameters. Distributions were also generated for a population assumed to represent the general population. RESULTS The following one-sided lower reference limits, the fifth centiles (with 95th percent confidence intervals), were generated from men whose partners had TTP < or = 12 months: semen volume, 1.5 ml (1.4-1.7); total sperm number, 39 million per ejaculate (33-46); sperm concentration, 15 million per ml (12-16); vitality, 58% live (55-63); progressive motility, 32% (31-34); total (progressive + non-progressive) motility, 40% (38-42); morphologically normal forms, 4.0% (3.0-4.0). Semen quality of the reference population was superior to that of the men from the general population and normozoospermic men. CONCLUSIONS The data represent sound reference distributions of semen characteristics of fertile men in a number of countries. They provide an appropriate tool in conjunction with clinical data to evaluate a patient's semen quality and prospects for fertility.

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World Health Organization reference values for human semen characteristics

WHO laboratory manual for the examination and processing of human semen

In this innovative book, a well-known feminist and sociologist-who is also the founding editor of Gender & Society-challenges our most basic assumptions about gender. Judith Lorber argues that gender is wholly a product of socialization, subject to human agency, organization, and interpretation, and that it is a social institution comparable to the economy, the family, and religion in its significance and consequences. Calling into question the inevitability and necessity of gender, she envisions a society structured for equality, where no gender, racial ethnic, or social class group is allowed to monopolize positions of power.

Paradoxes of gender

http://directory.umm.ac.id/Data%20Elmu/jurnal/A/Animal%20Reproduction%20Science/Vol60-61.Issue1-4.Jul2000/1971.pdf

The causes of reduced fertility with cryopreserved semen

High doses of gonadotropins have no detrimental effect on in vitro fertilization outcome in normal responders

On an egg-by-egg basis, normal human reproduction is an inefficient process. The indirect methods to determine this suggest that only about every fourth or fifth egg-sperm interaction results in a live birth (Wilcox et al., 1985; Zinaman et al., 1985). This is, of course, an average estimate and depends on many variables, the principal one of which is age. 

A 21st century study (Wang et al., 2003) calculated that among 441 subjects who averaged 24.9 years of age there was only a 30.1% chance of having a term pregnancy on the first exposure, even when explicitly trying to get pregnant.

In vivo in the human, there is no possibility to examine material from loss at the early cleavage stages. A majority of the failures seem to occur at this early stage. However, material has been studied from early clinical pregnancy losses. In one study, abnormalities were demonstrated at the chromosome level in approximately two-thirds of the specimens (Lathi et al., 2008). Another large study comparing aneuploidy in spontaneous loss vs loss after ART found 55.14% abnormalities from spontaneous and 51.88% after ART (Martinez et al., 2010).

While normal human reproduction seems to be quite inefficient, on an egg-by-egg basis reproduction by in vitro fertilization seems to be even more inefficient.

Reproductive efficiency of human eggs fertilized in vitro on an egg-to-egg basis is a seldom used evaluation of clinical assisted reproductive technology.

However, there have been a number of studies on this point (Inge et al., 2005; Meniru and Craft, 1997; Patrizio et al., 2007). It seems that only about 5% of harvested mature oocytes produce a live baby.

The purposes of this study are to determine if our own data confirm previous studies on the efficiency of eggs fertilized in vitro, to compare the inefficiency of normal human reproduction with the inefficiency of clinical IVF on an egg basis and to point out the implications of these inefficiencies.

Reproductive efficiency of human oocytes fertilized in vitro.

The present invention discloses biomarkers and biomarker combinations that have prognostic value as predictors of the developmental potential of individual IVF-derived human embryos. In particular, the biomarkers of this invention are useful to classify an embryo with implantation competence after uterine transfer or implantation incompetence. In addition, the biomarkers can be detected by non-invasive methods that do not harm the developing embryo. Also disclosed are kits for the prediction of developmental potential that detect the biomarkers of the invention, as well as methods using a plurality of classifiers to make a probable diagnosis of developmental potential.

Proteomic fingerprinting of human ivf-derived embryos: identification of biomarkers of developmental potential

OBJECTIVE The aim of this study was to compare the endometrial expression of milk fat globule-EGF factor 8 (MFG-E8), its receptor integrin αvβ3, and leukemia inhibitory factor (LIF) in patients with endometriosis and infertility and in healthy fertile patients during the window of implantation. METHODS Five patients with peritoneal endometriosis and infertility (case group) and four healthy fertile patients (control group) were recruited. All patients were either diagnosed with or ruled out for endometriosis by laparoscopic surgery; the case group underwent surgery for infertility investigation and the control group for tubal ligation. Endometrial biopsies were performed in all patients during the window of implantation (LH+8 to LH+10), and then the samples were analyzed by immunochemistry for MFG-E8, integrin αvβ3, and LIF. RESULTS In patients with endometriosis and infertility, expression of MFG-E8 was significantly increased in the glandular epithelium when compared to healthy fertile patients (p<0.001). Moreover, LIF expression was lower in patients with endometriosis and infertility (p<0.05). Nevertheless, we found no difference in integrin αvβ3 expression between the groups (p=0.084). CONCLUSION This study showed for the first time that MFG-E8 expression is impaired in the endometrium of patients with endometriosis and infertility during the window of implantation. Moreover, LIF is also diminished in the endometrium of these patients as shown before.

Alterations in expression of endometrial milk fat globule-EGF factor 8 (MFG-E8) and leukemia inhibitory factor (LIF) in patients with infertility and endometriosis.

The ZP2 protein is a zona pellucida glycoprotein that plays a major role in fertilization. It mediates secondary binding of spermatozoa and is one of the proteins that are involved in zona 'hardening'. ZP2 proteins were identified in various mammalian zonae pellucidae. Their primary structures are highly conserved as revealed by cDNA cloning. Antisera were used against synthetic peptides generated either against a ZP2 amino acid that is homologous in human and mouse ZP2 amino acid sequences (AS ZP2-20) or antibodies against a synthetic human ZP2 peptide (AS ZP2-26). Immunoblots showed that antiserum AS ZP2 20 and AS ZP2-26 strongly recognized human ZP2 protein with an apparent molecular mass of about 72 kDa; both antisera reacted with a minor immunoreactive polypeptide at 96 kDa. In human ovary sections, both antiscra revealed immunoreactivity to human zonae pellucidae. Immuno-electron microscopy demonstrated an equal distribution of ZP2 throughout the human zona pcllucida. Considerable amounts of immunoreactive material were observed in the ooplasm; some ramification-like extensions of zona pellucida antigen were found close to cells surrounding the oocyte. Our results indicate that antisera against synthetic ZP2 peptides can be used as specific markers for the identification of ZP2 protein in human oocytes.

Sergio Oehninger

Papers

High doses of gonadotropins have no detrimental effect on in vitro fertilization outcome in normal responders

Reproductive efficiency of human oocytes fertilized in vitro.

Proteomic fingerprinting of human ivf-derived embryos: identification of biomarkers of developmental potential

Alterations in expression of endometrial milk fat globule-EGF factor 8 (MFG-E8) and leukemia inhibitory factor (LIF) in patients with infertility and endometriosis.

Immunological identification of zona pellucida 2 (ZP2) protein in human oocytes