The neurohypophysial peptide oxytocin (OT) and OT-like hormones facilitate reproduction in all vertebrates at several levels. The major site of OT gene expression is the magnocellular neurons of the hypothalamic paraventricular and supraoptic nuclei. In response to a variety of stimuli such as suckling, parturition, or certain kinds of stress, the processed OT peptide is released from the posterior pituitary into the systemic circulation. Such stimuli also lead to an intranuclear release of OT. Moreover, oxytocinergic neurons display widespread projections throughout the central nervous system. However, OT is also synthesized in peripheral tissues, e.g., uterus, placenta, amnion, corpus luteum, testis, and heart. The OT receptor is a typical class I G protein-coupled receptor that is primarily coupled via Gq proteins to phospholipase C-β. The high-affinity receptor state requires both Mg2+ and cholesterol, which probably function as allosteric modulators. The agonist-binding region of the receptor has bee...

The Oxytocin Receptor System: Structure, Function, and Regulation

Some tissue types give rise to human cancers millions of times more often than other tissue types. Although this has been recognized for more than a century, it has never been explained. Here, we show that the lifetime risk of cancers of many different types is strongly correlated (0.81) with the total number of divisions of the normal self-renewing cells maintaining that tissue’s homeostasis. These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions. The majority is due to “bad luck,” that is, random mutations arising during DNA replication in normal, noncancerous stem cells. This is important not only for understanding the disease but also for designing strategies to limit the mortality it causes.

https://science.sciencemag.org/content/sci/347/6217/78.full.pdf

Variation in cancer risk among tissues can be explained by the number of stem cell divisions

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

The sperm chromatin structure assay (SCSA) was used to measure over 500 human semen samples from two independent studies: Study I, 402 samples from 165 presumably fertile couples wishing to achieve pregnancy over 12 menstrual cycles; Study II, samples from 115 patients seeking fertility counselling. The SCSA measures susceptibility to DNA denaturation in situ in spermatozoa exposed to acid for 30 s, followed by acridine orange staining. SCSA data from the male partners of 73 couples (group 1) achieving pregnancy during months 1‐3 of Study I were used as the standard of ‘sperm chromatin compatible with high fertility’ and were significantly different from those of 40 couples (group 3) achieving pregnancy in months 4‐12 (P < 0.01) and those of male partners of 31 couples (group 4) not achieving pregnancy (P < 0.001). Group 2 contained couples who had a miscarriage. SCSA values for Study II were almost twice that of the Study I fertility standards. Within-couple repeatability tended to be less for group 3 than for groups 1, 2 or 4. Based on logistic regression, spermatozoa with denatured DNA (cells outside the main population, COMPa t) were the best predictor for whether a couple would not achieve pregnancy. Some 84% of males in group 1 had COMPat <15%, while no couples achieved pregnancy in group 1 with ‡30% COMPat, a threshold level considered not compatible with good fertility. Using selected cut-off values for chromatin integrity, the SCSA data predicted seven of 18 miscarriages (39%).

Utility of the sperm chromatin structure assay as a diagnostic and prognostic tool in the human fertility clinic

Mitochondrial membrane potential.

Computer-assisted sperm analysis (CASA): capabilities and potential developments.

This paper highlights the most critical aspects of the problem of predicting fertility. To determine if a laboratory test(s) is highly correlated with fertility it is essential to have: a) specific, precise and accurate laboratory tests, and b) precise and accurate fertility data. Acquisition of precise and accurate data for laboratory tests and fertility of spermatozoa in the same sample is not easy. Data derived from in vitro fertilization are not tests of fertility, because only a subset of the attributes important for fertilization in vivo are tested. Because of deficiencies in fertility data, there probably is no valid report for human spermatozoa correlating results of laboratory tests and fertility, and very few valid studies for laboratory or domesticated animals. There is little doubt that objective measures of sperm motion, acrosomal status, or other characteristics are significantly correlated with fertility. However, establishment of the correlations between a group of attributes and fertility is not the question of interest. The goal is prediction of fertility. There has been no recent effort to develop a prediction of fertility or fecundity based on sperm characteristics, and achievement of this goal may be elusive.

Can the fertility potential of a seminal sample be predicted accurately

https://onlinelibrary.wiley.com/doi/pdf/10.1002/j.1939-4640.1981.tb00595.x

A Critical Review of Methods for Evaluation of Spermatogenesis from Seminal Characteristics

Understanding the dynamics of spermatogenesis is central to clinical andrology or to probing environmental effects on human testes. This review considers what is known about renewal and proliferation of spermatogonia, how germ cells are organized in cellular associations constituting the cycle of the seminiferous epithelium, relative frequencies of cellular associations, durations of the cycle of the seminiferous epithelium and spermatogenesis, and measurement of daily sperm production. Daily sperm production (DSP) per testis tends to decline with advancing age. Regardless of age, there is substantial loss of potential sperm from degeneration of spermatocytes, but not spermatids. DSP per gram testis parenchyma or DSP per testis cannot be predicted on the basis of testis size or age of a man. The review shows why our 1960s data base is neither robust nor precise and suggests how deficiencies might be rectified. New cellular associations should be defined, with none representing >15% of the cycle of the seminiferous epithelium. Then determine when Apale-spermatogonia become committed to proliferate or how many mitotic divisions occur thereafter. Restudy the duration of spermatogenesis because the accepted value might be in error by ∼6 days. Restudying human spermatogenesis will benefit clinicians, toxicologists, and epidemiologists probing testis function by direct evaluations or indirectly via evaluations of quantity and quality of sperm ejaculated. It also will benefit scientists interested in renewal and proliferation of spermatogonia, or a spermatogonium as a prototype stem cell.

https://onlinelibrary.wiley.com/doi/pdf/10.2164/jandrol.107.004655

Rupert P. Amann

Papers

Computer-assisted sperm analysis (CASA): capabilities and potential developments.

Can the fertility potential of a seminal sample be predicted accurately

Can the fertility potential of a seminal sample be predicted accurately

A Critical Review of Methods for Evaluation of Spermatogenesis from Seminal Characteristics

The cycle of the seminiferous epithelium in humans: a need to revisit?