Foreskin

The expression of mitochondrial components is controlled by an intricate interplay between nuclear transcription factors and retrograde signaling from mitochondria. The role of mitochondrial DNA (mtDNA) and mtDNA-encoded proteins in mitochondrial biogenesis is, however, poorly understood and thus far has mainly been studied in transformed cell lines. We treated primary human fibroblasts with ethidium bromide (EtBr) or chloramphenicol for six weeks to inhibit mtDNA replication or mitochondrial protein synthesis, respectively, and investigated how the cells recovered from these insults two weeks after removal of the drugs. Although cellular growth and mitochondrial gene expression were severely impaired after both inhibitor treatments we observed marked differences in mitochondrial structure,membrane potential, glycolysis, gene expression, and redox status between fibroblasts treated with EtBr and chloramphenicol. Following removal of the drugs we further detected clear differences in expression of both mtDNA-encoded genes and nuclear transcription factors that control mitochondrial biogenesis, suggesting that the cells possess different compensatory mechanisms to recover from drug-induced mitochondrial dysfunction. Our data reveal new aspects of the interplay between mitochondrial retrograde signaling and the expression of nuclear regulators of mitochondrial biogenesis, a process with direct relevance to mitochondrial diseases and chloramphenicol toxicity in humans.

Excerpt from the American Journal of Sexual Medicine reviewer's "comments to the author":
"Reading between the lines, it is clear that this is a political statement against circumcision masquerading as a medical definition of the foreskin as an organ. Although the authors’ pain and outrage are obvious, I really do not empathize. So what if the foreskin is a lip? Their deeper argument that its removal impoverishes the sexual lives of men does not rest on any solid scientific foundation."
(Being the owner of a healthy and efficient prepuce, the author wouldn't give it away for an empire.)

A review of the medical literature about the sexual functions of the foreskin

BACKGROUND
Elementary medical ethics forbids the excision of an organ without strict and serious medical motive.

METHODS
After the exposure of the concept of lip, its appliance to the foreskin makes the latter a full organ. Then, the article recalls the main medical literature that sets out the two functions of the foreskin: sexual and protective.

RESULTS
This article emphasizes that the foreskin is a full organ: the specific organ for autosexuality, an adjuvant for heterosexuality and the protective lip of the glans.

CONCLUSION
Anatomy has not generalized the notion of lip to all the organs with a similar structure and function. First, highlighting that the foreskin is a lip emphasizes its function of indispensable organ for protecting the glans. Second, the review of medical literature recalls that the foreskin includes an erogeneity and an ability to retract that make it not only the specific organ for solitary sexuality but also a useful tool of heterosexuality. Third: the concept of autosexuality replaces an insidiously making guilty and derogatory concept by a neutral one. So, this article brings medicine two useful concepts and takes the defence of a sometimes hastily neglected sexual organ.

Keywords: anatomy, organ, lip, foreskin, sexual function, circumcision, mutilation.

What are the effects of circumcision  on sexual function and experience? And what does sex—in the sense related to gender—have to do with the ethics of circumcision? Jacobs and Arora (2015) give short shrift to the first of these questions; and they do not seem to have considered the second. In this commentary, I explore the relationship between sex (in both senses) and infant male circumcision, and draw some conclusions about the ongoing debate regarding this controversial practice.

Withstanding the test of time, male circumcision remains the oldest and most widely used procedure on the globe, spanning over six millennia and six continents, yet, little factual information about its origin, values, persistence, and ramifications is known by its most devout adherents, namely, the American people. By examining circumcision's evolutionary past, it

Feldblum et al. (2015) argue that voluntary medical male circumcision (VMMC) using the ShangRing device leads to increased sexual pleasure, universally satisfying cosmetic outcome, and virtually no delayed complications in a 2-3 year follow-up study. In this commentary, I suggest that socially desirable responding (SDR) is a likely candidate explanation for at least some of these reported findings, and I argue that this should have been controlled for using available measures. I also highlight evidence from the authors’ own study for risk compensation as a result of circumcision (including decreased condom use and an increase in number of sexual partners) and ask why this adverse outcome was not emphasized as a cause for concern. I conclude by providing 6 concrete suggestions for improving future studies on circumcision.

In their review article, Clark et al. claim, "Neonatal circumcision is medically necessary and ethically imperative" [1].  This represents a double contradiction of, among others, the positions of the American Academy of Pediatrics [2], the British Medical Association [3], the Canadian Paediatric Society [4], and the Royal Australasian College of Physicians [5].

To justify such a dramatic conclusion, the authors need to make a strong case.  This is all the more true given the authors' far-reaching intent to examine the medical evidence, give an ethical analysis, and develop guidelines to implement mandatory neonatal circumcision in sub-Saharan Africa.  Unfortunately the authors stumble so badly on the first two steps that the third step becomes irrelevant.  We will evaluate the accuracy and quality of the "medical evidence" Clark et al. use in their analysis by parsing the facts from the fantasy, providing an overview of the risk-benefit analyses of circumcision, and providing our own modest proposal.

The essay offers a critical examination of the tendency to segregate discussion of surgical alterations to the male and female genitals into separate compartments -- the first known as circumcision, the second as genital mutilation.  It is argued that this fundamental problem underlies the considerable controversy surrounding these procedures when carried out on minors, and that it hinders objective discussion of the alleged benefits, harms and risks.  The variable effects of male and female genital surgeries are explored, and a scale of damage for male circumcision to complement the World Health Organization's categorization of female genital mutilation is proposed.  The origins of the double standard identified are placed in historical perspective, and a brief conclusion makes a plea for greater gender neutrality in the approach to this contentious issue.

Introduction. The question of whether removal of sensory receptors in the prepuce by circumcision affects sensitivity and/or sexual pleasure is often debated.
Aims. To examine histological correlates relevant to penile sensitivity and sexual pleasure.
Methods. Systematic review of the scientific literature on penile structures that might affect sensitivity and sexual sensation. Articles were included if they contained original data on human male penile histology or anatomy. Individual articles, including reference lists, were evaluated. They were then considered in relation to physiological data from articles retrieved by a previous systematic review.
Results. We retrieved 41 publications on penile structure. Considered in the light of 12 reporting physiological measurements, our evaluation finds that sexual response is unlikely to involve Meissner’s corpuscles, whose density in the prepuce diminishes at the time of life when male sexual activity is increasing. Free nerve endings also show no correlation with sexual response. Because tactile sensitivity of the glans decreases with sexual arousal, it is unrelated to sexual sensation. Thermal sensitivity seems part of the reward mechanism of intercourse. Vibrational sensitivity is not related to circumcision status. Observations that penile sexual sensation is higher post circumcision are consistent with greater access of genital corpuscles to sexual stimuli after removal of the prepuce. This is based on the distribution of these corpuscles (which are located in the glans) and, in uncircumcised men, the position of the retracted prepuce during intercourse, rather than any change in the number of genital corpuscles. The scientific literature suggests that any sexual effect of circumcised men may depend solely on exposure of the glans and not on the absence of the prepuce.
Conclusion. Based on histological findings and correlates of sexual function, loss of the prepuce by circumcision would appear to have no adverse effect on sexual pleasure. Our evaluation supports overall findings from physiological measurements and survey data.
Cox G, Krieger JN, and Morris BJ. Histological correlates of penile
sexual sensation: Does circumcision make a difference? Sex Med 2015;3:76–85.
Key Words. Circumcision; Prepuce; Glans Penis; Sexual Satisfaction; Penile Sensation; Genital Corpuscles; Meissner’s Corpuscles; Free Nerve Endings; Neurophysiology; Orgasm; Male Sexual Pleasure

This article surveys the various ways that male genitalia are cut or altered without medical necessity, often for cultural or religious reasons. In addition to some attention to classification, the focus will be on motivations and justifications for male genital cutting in specific populations, and in specific epochs. Considerable variation in practices and motives/justifications is observed: some forms are extremely rare, some very common in certain societies, tribes, and/or religions. The role of a lack of knowledge of the anatomy and function(s) of the surgically unmodified penis, in particular the prepuce or foreskin, is also considered.

Excerpt from the American Journal of Sexual Medicine reviewer's "comments to the author":
"Reading between the lines, it is clear that this is a political statement against circumcision masquerading as a medical definition of the foreskin as an organ. Although the authors’ pain and outrage are obvious, I really do not empathize. So what if the foreskin is a lip? Their deeper argument that its removal impoverishes the sexual lives of men does not rest on any solid scientific foundation."
(Being the owner of a healthy and efficient prepuce, the author wouldn't give it away for an empire.)

A review of the medical literature about the sexual functions of the foreskin

BACKGROUND
Elementary medical ethics forbids the excision of an organ without strict and serious medical motive.

METHODS
After the exposure of the concept of lip, its appliance to the foreskin makes it a full organ. Then, the article recalls the main medical literature that sets out the two functions of the foreskin: sexual and protective.

RESULTS
This article emphasizes that the foreskin is a full organ: the specific organ for autosexuality, an adjuvant for heterosexuality and the protective lip of the glans.

CONCLUSION
Anatomy has not generalized the notion of lip to all the organs with a similar structure and function. First, highlighting that the foreskin is a lip emphasizes its function of indispensable organ for protecting the glans. Second, the review of medical literature recalls that the foreskin includes an erogeneity and an ability to retract that make it not only the specific organ for solitary sexuality but also a useful tool of heterosexuality. Third: the concept of autosexuality replaces an insidiously making guilty and derogatory concept by a neutral one. So, this article brings medicine two useful concepts and takes the defence of a sometimes hastily neglected sexual organ.

Keywords: anatomy, organ, lip, foreskin, sexual function, circumcision, mutilation.

Aims:  To investigate the effects of anthrax lethal toxin (LeTx) on human primary keratinocytes.Methods and Results:  We show here that human primary keratinocytes are resistant to LeTx-triggered cytotoxicity. All but one of the MEKs (mitogen-activated protein kinase kinases) are cleaved within 3 h, and the cleavage of MEKs in keratinocytes leads to their subsequent proteasome-mediated degradation at different rates. Moreover, LeTx reduced the concentration of several cytokines except RANTES in culture.Conclusions:  Our results indicate that primary keratinocytes are resistant to LeTx cytotoxicity, and MEK cleavage does not correlate with LeTx cytotoxicity. Although LeTx is considered as an anti-inflammatory agent, it upregulates RANTES.Significance and Impact of the Study:  According to a current view, the action of LeTx results in downregulation of the inflammatory response, as evidenced by diminished expression of several inflammatory biomarkers. Paradoxically, LeTx has been reported to attract neutrophils to cutaneous infection sites. This paper, which shows that RANTES, a chemoattractant for immune cells, is upregulated after exposure of keratinocytes to LeTx, although a number of other markers of the inflammatory response are downregulated. Our results might explain why the exposure of keratinocytes to LeTx results in the recruitment of neutrophils to cutaneous infection sites, while the expression of several inflammatory biomarkers is diminished.

Bossio et al. (in press) report that circumcision does not reduce sensitivity of the penis. However, their own results show that the foreskin is the most sensitive part of the penis to tactile stimulation, as well as more sensitive to warmth than the penile glans. Since the foreskin is (a) the most touch-sensitive part of the penis, and (b) it is removed by circumcision, circumcision reduces sensitivity of the penis by definition. Further problems with the study by Bossio et al. are discussed.

Introduction. The prepuce envelops the glans as a variant of a mucocutaneous tissue presenting with a lot of functions, the most important of them being to protect the infant?s glans from feces and ammonia in diapers, to protect the glans from abrasions and trauma throughout life, and to provide sufficient skin in erection. Circumcision was recognized as a method of solving foreskin problems a long time before Christ. Practicing male circumcision in history was customary several thousand years ago and has spread worldwide. Today it depends on races, and it is often an initiation ceremony near the age of puberty. In everyday practice in pediatric urology outpatient department the foreskin problems have been noticed as a phimosis in 9.91% cases and prepuce adhesions in 3.98%. Congenital anomalies are present in different numbers. Other problems, such as paraphimosis, balanoposthitis, are recorded as accidental cases. Over-all prepuce pathology can be observed in 12%-25% of patients. T...