- Open Access
Lifestyle impact and the biology of the human scrotum
© Ivell; licensee BioMed Central Ltd. 2007
- Received: 08 March 2007
- Accepted: 20 April 2007
- Published: 20 April 2007
The possession of a scrotum to contain the male gonads is a characteristic feature of almost all mammals, and appears to have evolved to allow the testes and epididymis to be exposed to a temperature a few degrees below that of core body temperature. Analysis of cryptorchid patients, and those with varicocele suggest that mild scrotal warming can be detrimental to sperm production, partly by effects on the stem cell population, and partly by effects on later stages of spermatogenesis and sperm maturation. Recent studies on the effects of clothing and lifestyle emphasize that these can also lead to chronically elevated scrotal temperatures. In particular, the wearing of nappies by infants is a cause for concern in this regard. Together all of the evidence indirectly supports the view that lifestyle factors in addition to other genetic and environmental influences could be contributing to the secular trend in declining male reproductive parameters. The challenge will be to provide relevant and targeted experimental results to support or refute the currently circumstantial evidence.
- Leydig Cell
- Testicular Cancer
- Stem Cell Population
The exteriorization of the male gonads in a special sac called the scrotum is a uniquely mammalian feature, and one that at first glance requires some explanation. Surely, a trait that would place all of the genetic material essential for procreation in such an exposed situation, rather than protecting it deep within the organism (e.g. like the ovaries) must have some important selective advantage; otherwise why could it evolve and why has it not been selected against. The most plausible evolutionary explanation relates to the requirement of spermatogenesis for an optimum temperature lower than core abdominal temperature . Certainly, the temporary exposure of the adult testes to mild warming (abdominal temperature) leads to marked disruption of spermatogenesis and/or male fertility [2, 3]. Testicular descent into a scrotum evolved probably more than 150 million years ago concurrently with the acquisition by ancestral mammals of a regulated hyperthermia , which provided the abdominal organs with a controlled, stable body temperature of ca. 36–38°C. It is notable that in many mammals which have reverted to having abdominal testes, either there is a specialized blood supply acting as a heat exchanger to cool the abdominal gonad (e.g. whales), or the core temperature is itself relatively low 34–36°C (e.g. some insectivores) . Although elephants appear to have abdominal testes as a primitive trait, there is recent evidence to suggest that they may have had an aquatic origin in the distant past , possibly at a time of early mammalian radiation, when the scrotal trait was not fully established in all mammalian lineages.
There are two common pathologies associated with testicular heating: cryptorchidism and varicocele. In cryptorchidism, due to a variety of causes, one or both testes may be retained within the abdominal cavity or within the inguinal canal rather than descending normally into the scrotum, which in humans logically occurs at birth. Testicular descent in humans is separated into two major phases [8, 9]. The first phase, which occurs during pregnancy, is characterized by a relocation of the testes from a more dorsal perirenal position to one in the inguinal region of the body cavity. This is achieved by dissolution, under the influence of androgens, of the cranial suspensory ligament securing the fetal testes dorsally, and most importantly a growth and development of the ventrally located gubernacular ligament . This is the result of a combination of androgen action, some effect of the peptide Anti-Mullerian Hormone (AMH), and most importantly the relaxin-like male hormone, Insulin-like peptide 3 (INSL3) [9–11]. The role of AMH in testicular descent is unclear, whilst there appears to be a small in vitro effect on gubernacular growth , most studies show no influence of this hormone [10, 12]. How the testes enter the scrotum is not well understood, though a considerable body of evidence shows that the majority of children whose testes are descended into the inguinal region, but cannot progress further, can be successfully treated by stimulating the hypothalamo-pituitary-gonadal axis, either by GnRH (gonadotropin releasing hormone) analogues or by hCG (human chorionic gonadotropin) [8, 13, 14]. This is usually interpreted to imply that also this phase is under androgen control, but since this treatment serves to stimulate Leydig cell differentiation and activity, it might also imply that other Leydig cell products, of which INSL3 is one, might also be involved.
The detailed mechanisms operating at a cellular or molecular level are unclear. This is partly due to the fact that it is not possible to distinguish between effects due to unnatural heating of the postnatal testis, and factors which led to cryptorchidism in the first place. So, for example, whilst it appears that Adark spermatogonia are negatively affected by postnatal warming, these cells or their progenitor gonocytes may also be targets of the same endocrine disruptors that can affect male differentiation in utero, leading also to gonocyte transformation and the formation of carcinoma-in-situ (CIS) cells, which are the seeds of later seminomas . Similarly, a common feature of the perinatal cryptorchid testis are poorly functioning Leydig cells, and hence reduced androgen levels in the so-called perinatal "minipuberty" . It is known that endocrine disruptors such as phthalates can lead to both reduced Leydig cell function and to cryptorchidism [23–25]. Therefore, at this stage in time, we cannot state what are pure effects due only to unnatural testicular heating in early childhood, and what may be effects linked to the original cause of the cryptorchidism.
To complicate the issue further, there may be circumstances where an increase of testicular temperature to that of the abdomen appears to be advantageous. For example, in the jsd/jsd mouse, which has impaired spermatogenesis due to a mutation in the mUtp14b gene, retention of the testis in the abdomen actually rescues the arrest of spermatogonial differentiation, thus partly restoring spermatogenesis . However, more extensive studies show that the higher temperature is actually causing a subtle androgen-control system to be down-regulated, and that the activated androgen receptor is mediating the arrest of spermatogenesis in this mutant . Thus this mutant does not contradict the generally negative effects of abdominal temperature on testis function.
In varicocele, there is large varicose distension of venous blood vessels within the scrotum, usually associated with increased blood flow [28, 29]. One physiological consequence of this, besides increased oxidative stress, is also increased local temperature of the testis, and hence impairment of spermatogenesis [28–31].
It has long been a source of investigation and speculation that the adoption of certain styles of clothing and posture can influence testicular function, and in particular spermatogenesis. The importance of clothing style and its tightness remains controversial (reviewed in [32, 33]), as also is the influence of hot baths, saunas, etc. However, given that the natural cooling methods for the scrotum rely on sweating and vasomotor changes , it is now very clear that clothing in combination with behaviour or posture can have significant effects. Normal scrotal temperature (the external surface of the scrotum) is approximately 34°C in a normally clothed man walking about or maintaining a loose stance, and it has been estimated that testicular temperature within the scrotum is between 0.1 and 0.6°C higher than this [32, 35, 36]. Clothing itself appears to contribute about 0.5–1.0°C , compared to being naked. Clothed and sitting down with thighs apart raises scrotal temperature to about 35 C, whereas sitting with thighs together quickly allows scrotal temperature to rise to above 36 C, i.e. to abdominal temperature within the testis . Several studies have now shown that men with predominantly sedentary occupations , or who spend considerable time driving a vehicle [38, 39], have higher average scrotal temperatures and consequently lower average sperm production or reduced fertility. Another situation where scrotal temperatures become elevated is during sleep, when bedclothes and lack of movement prevent ventilation. Men with oligozoospermia or oligoasthenozoospermia who were allowed to sleep with a small apparatus which permitted nocturnal scrotal cooling showed significant improvements in semen quality over a period of 12 weeks [32, 33]. This time is required to allow positive effects on all stages of spermatogenesis, including stem cells to become manifest in the ejaculate. Taken together, these studies all indicate that a more sedentary lifestyle can and most likely does cause a significant impairment in sperm production and quality.
All of the preceding studies relate to testis function in the adult. There is far less known about the impact of lifestyle factors on the important prepubertal and perinatal stages of reproductive development. This is the period when the endocrine axes become established and the functionality of individual cell components of the testis is determined. Besides the generally negative effects of sedentary habits on children in the context of their later developing symptoms of obesity and metabolic syndrome (e.g. ), continual over-heating of the testes are likely to impact also on the establishment of spermatogenesis during adolescence. Possibly more significant than this, however, are the consequences on reproductive parameters of the wearing of nappies (diapers) in infancy. Nappy use leads to a long-term increase in scrotal temperature of 1–2 C, compared to air-exposure [41, 42]. There appears to be little difference between the use of modern disposable nappies and old-fashioned cloth nappies used together with a plastic cover. If these become wet or soiled, then a further increase in scrotal temperature may be recorded . Dry cloth nappies without any covering only appear to have a small effect on scrotal temperature . Babies are often sedentary or asleep for long periods and nappies may become soiled or wet for much of this time. Nappy usage can extend for several years at a time when the testes may be establishing their reproductive potential. If we consider the risks to the Adark spermatogonial stem cell population that may be incurred by a delay in surgically descending cryptorchid testes (see above), then the usage of modern disposable nappies may also be incurring similar long term consequences to the reproductive potential of future men. Since cryptorchidism is associated with testicular cancer, one recent study has looked at whether nappy-wearing has consequences in terms of testicular cancer risk . In this retrospective study, no association was found. However, as mentioned above, there is no evidence to show that it is testicular heating rather than some common intrauterine cause which leads to CIS cells and resultant testicular cancer.
All studies to date relate to experiments carried out in adult-type systems. There is no information about effects of scrotal temperature on the early development of the epididymis or its functions, or whether long-term exposure to higher temperatures early in life could elicit adaptive processes of benefit in adulthood.
There is currently worldwide concern over possible effects of endocrine disrupting agents, with much evidence pointing to an impact by such xenobiotics on the developing fetus in utero. In the context of male reproduction there appears to be a recognized association between xenobiotic exposure and traits such as hypospadias, cryptorchidism, CIS and testicular cancer, and reduced anogenital distance [25, 46]. In animal experiments, where rats have been given high doses of phthalates, this extends also to reduced adult sperm production. Whether xenobiotic exposure of the male fetus is responsible for the sometimes considerably reduced human sperm counts in some European countries is still debatable. A key feature of traits such as low sperm counts is that the trends are consistently increasing over long periods of time, indicating clear cohort effects, and regionally different rates of change. Together, these features point to an environmental influence, which is associated with increased industrialization. More recently, a similar trend has been reported in the context of the Massachussetts male ageing study, for the total circulating testosterone. This appears to be declining in ageing men in a cohort-dependent manner, which is independent of other lifestyle confounders .
The accumulated evidence is highly compelling that the scrotum has evolved in order to provide a local environment for sperm production, maturation and storage that is several degrees cooler than core body temperature. A failure to cool the scrotum adequately appears to be associated in the adult with impaired spermatogenesis, in young boys possibly also to a reduced gonadal stem cell population. Lifestyle factors such as clothing, posture, sedentary behaviour, and the wearing of nappies by babies all seem to predicate a worsening of male reproductive parameters, possibly contributing amongst other factors to the secular trends observed in sperm counts across the globe.
However, most of the evidence is circumstantial, and at least one author  has suggested that a direct proof of such effects remains "untestable" in the context of evidence-based medicine. The reasons for this are largely due to the uniqueness of the human situation. There are few experimental animal models which can be considered comparable or appropriate for the human. We undergo a period of relative testicular quiescence of more than 8 years from birth until the beginnings of puberty, when possible negative influences on scrotal temperature could impact subtly upon stem cell populations, as well as during the whole adult lifespan. Rodent models exhibit a comparable prepubertal period of barely 2 weeks, whilst other models such as sheep or dogs can extend this to a period of up to 2–3 months. These are time periods which are biologically not comparable. Add to this that the human species appears to have a fundamental, genetic impairment of spermatogenesis compared to domestic and laboratory species which have been bred for fertility and fecundity. There are indeed a number of mutations in fertility genes in the human, which are considered important in other species [49, 50], suggesting that humans as a species are essentially subfertile, and thus more predisposed to subtle negative environmental influences. Epidemiological studies also appear to be highly problematic, largely because of an absence of appropriate matched control groups, i.e. who do not wear clothes, or wear no nappies of any kind, etc.
We are therefore confronted with a difficult problem. Until direct rather than circumstantial evidence can be produced, current lifestyle habits and conveniences will prevail, probably to the detriment of our reproductive capacity. This is the core tenet of evidence-based medicine. The challenge therefore must be met to devise the experiments which will convincingly provide that evidence or refute the possibility.
I should like to acknowledge the friendly support of my colleagues in the Research Centre for Reproductive Health, and especially the inspiring discussions with Professor Brian Setchell, who has pioneered research into heating effects of the testis. I am also indebted to the National Health and Medical Research Council of Australia, and the Australian Research Council for funding support of my research.
- Werdelin L, Nilsonne A: The evolution of the scrotum and testicular descent in mammals: a phylogenetic view. J Theor Biol. 1999, 196: 61-72. 10.1006/jtbi.1998.0821.View ArticlePubMedGoogle Scholar
- Setchell BP: The Parkes lecture. Heat and the testis. J Reprod Fertil. 1998, 114: 179-194.View ArticlePubMedGoogle Scholar
- Yaeram J, Setchell BP, Maddocks S: Effect of heat stress on the fertility of male mice in vivo and in vitro. Reprod Fertil Dev. 2006, 18: 647-653. 10.1071/RD05022.View ArticlePubMedGoogle Scholar
- Gaeth AP, Short RV, Renfree MB: The developing renal, reproductive, and respiratory systems of the African elephant suggest an aquatic ancestry. Proc Natl Acad Sci USA. 1999, 96: 5555-5558. 10.1073/pnas.96.10.5555.PubMed CentralView ArticlePubMedGoogle Scholar
- Short RV: The testis: the witness of the mating system, the site of mutation and the engine of desire. Acta Paediatr Suppl. 1997, 422: 3-7.View ArticlePubMedGoogle Scholar
- Bedford JM: Anatomical evidence for the epididymis as the prime mover in the evolution of the scrotum. Am J Anat. 1978, 152: 483-507. 10.1002/aja.1001520404.View ArticlePubMedGoogle Scholar
- Freeman S: The evolution of the scrotum: a new hypothesis. J Theor Biol. 1990, 145: 429-445. 10.1016/S0022-5193(05)80479-5.View ArticlePubMedGoogle Scholar
- Hutson JM, Hasthorpe S, Heyns CF: Anatomical and functional aspects of testicular descent and cryptorchidism. Endocr Rev. 1997, 18: 259-280. 10.1210/er.18.2.259.PubMedGoogle Scholar
- Ivell R, Hartung S: The molecular basis of cryptorchidism. Mol Hum Reprod. 2003, 9: 175-181. 10.1093/molehr/gag025.View ArticlePubMedGoogle Scholar
- Emmen JM, McKuskey A, Adham IM, Engel W, Grootegoed JA, Brinkmann AO: Hormonal control of gubernaculums development during testis descent: gubernaculums outgrowth in vitro requires both insulin-like factor and androgen. Endocrinology. 2000, 141: 4720-4727. 10.1210/en.141.12.4720.PubMedGoogle Scholar
- Kubota Y, Temelcos C, Bathgate RA, Smith KJ, Scott D, Zhao C, Hutson JM: The role of insulin 3, testosterone, Mullerian inhibiting substance and relaxin in rat gubernacular growth. Mol Hum Reprod. 2002, 8: 900-905. 10.1093/molehr/8.10.900.View ArticlePubMedGoogle Scholar
- Lyet L, Vigier B, van der Schoot P: Anti-mullerian hormone in relation to the growth and differentiation of the gubernacular primordia in mice. J Reprod Fertil. 1996, 108: 281-288.View ArticlePubMedGoogle Scholar
- Giannopoulos MF, Vlachakis IG, Charissis GC: 13 years' experience with the combined hormonal therapy of cryptorchidism. Horm Res. 2001, 55: 33-37. 10.1159/000049961.View ArticlePubMedGoogle Scholar
- Hadziselimovic F: Cryptorchidism, its impact on male fertility. Eur Urol. 2002, 41: 121-123. 10.1016/S0302-2838(01)00040-9.View ArticlePubMedGoogle Scholar
- Rusnack SL, Wu HY, Huff DS, Snyder HM, Carr MC, Bellah RD, Zderic SA, Canning DA: Testis histopathology in boys with cryptorchidism correlates with future fertility potential. J Urol. 2003, 169: 659-662. 10.1016/S0022-5347(05)63986-9.View ArticlePubMedGoogle Scholar
- Dieckmann KP, Skakkebaek NE: Carcinoma in situ of the testis: a review of biological and clinical features. Int J Cancer. 1999, 83: 815-822. 10.1002/(SICI)1097-0215(19991210)83:6<815::AID-IJC21>3.0.CO;2-Z.View ArticlePubMedGoogle Scholar
- Kumagai J, Fukuda J, Kodama H, Murata M, Kawamura K, Itoh H, Tanaka T: Germ cell specific heat shock protein 105 binds to p53 in a temperature-senistive manner in rat testis. Eur J Biochem. 2000, 267: 3073-3078. 10.1046/j.1432-1033.2000.01336.x.View ArticlePubMedGoogle Scholar
- Hirai K, Sasaki H, Yamamoto H, Sakamoto H, Kubota Y, Kakizoe T, Terada M, Ochiya T: HST-1/FGF-4 protects male germ cells from apoptosis under heat-stress condition. Exp Cell Res. 2004, 294: 77-85. 10.1016/j.yexcr.2003.11.012.View ArticlePubMedGoogle Scholar
- Zhang XS, Lue YH, Guo SH, Yuan JX, Hu ZY, Han CS, Hikim AP, Swedloff RS, Wang C, Liu YX: Expression of HSP105 and HSP60 during germ cell apoptosis in the heat-treated testes of adult cynomolgus monkeys (macaca fascicularis). Front Biosci. 2005, 10: 3110-3121.View ArticlePubMedGoogle Scholar
- Hadziselimovic F, Herzog B: The importance of both an early orchidopexy and germ cell maturation for fertility. Lancet. 2001, 358: 1156-1157. 10.1016/S0140-6736(01)06274-2.View ArticlePubMedGoogle Scholar
- Skakkebaek NE, Rajpert De Meyts E, Main KM: Testicular dysgenesis syndrome an increasingly common developmental disorder with environmental aspects. Hum Reprod. 2001, 16: 972-978. 10.1093/humrep/16.5.972.View ArticlePubMedGoogle Scholar
- Hadziselimovic F, Zivkovic D, Bica DT, Emmons LR: The importance of mini-puberty for fertility in cryptorchidism. J Urol. 2005, 174: 1536-1539. 10.1097/01.ju.0000181506.97839.b0.View ArticlePubMedGoogle Scholar
- McKinnell C, Sharpe RM, Mahood K, Hallmark N, Scott H, Ivell R, Staub C, Jegou B, Haag F, Koch-Nolte F, Hartung S: Expression of insulin-like factor 3 protein in the rat testis during fetal and postnatal development and in relation to cryptorchidism induced by in utero exposure to di(n-Butyl)phthalate. Endocrinology. 2005, 146: 4536-4544. 10.1210/en.2005-0676.View ArticlePubMedGoogle Scholar
- Main KM, Mortensen GK, Kaleva MM, Boisen KA, Damgaard IN, Chellakooty M, Schmidt IM, Suomi AM, Virtanen HE, Petersen DV, Andersson AM, Toppari J, Skakkebaek NE: Human breast milk contamination with phthalates and alterations of endogenous reproductive hormones in infants three months of age. Environ Health Perspect. 2006, 114: 270-276.PubMed CentralView ArticlePubMedGoogle Scholar
- Foster PM: Disruption of reproductive development in male rat offspring following in utero exposure to phthalate esters. Int J Androl. 2006, 29: 140-147. 10.1111/j.1365-2605.2005.00563.x.View ArticlePubMedGoogle Scholar
- Shetty G, Weng CCY: Cryptorchidism rescues spermatogonial differentiation in juvenile spermatogonial depletion (Jsd) mice. Endocrinology. 2004, 145: 126-133. 10.1210/en.2003-0928.View ArticlePubMedGoogle Scholar
- Shetty G, Weng CCY, Porter KL, Zhang Z, Pakarinen P, Kumar TR, Meistrich ML: Spermatogonial differentiation in juvenile spermatogonial depletion (jsd) mice with androgen receptor or follicle-stimulating hormone mutations. Endocrinology. 2006, 147: 3563-3570. 10.1210/en.2006-0159.View ArticlePubMedGoogle Scholar
- Turner TT: The study of varicocele through the use of animal models. Hum Reprod Update. 2001, 7: 78-84. 10.1093/humupd/7.1.78.View ArticlePubMedGoogle Scholar
- Schoor RA, Elhanbly SM, Niederberger C: The pathophysiology of varicocele-associated male infertility. Curr Urol Rep. 2001, 2: 432-436.View ArticlePubMedGoogle Scholar
- Ali JI, Weaver DJ, Weinstein SH, Grimes EM: Scrotal temperature and semen quality in men with and without varicocele. Arch Androl. 1990, 24: 215-219.View ArticlePubMedGoogle Scholar
- Lerchl A, Keck C, Spiteri-Grech J, Nieschlag E: Diurnal variations in scrotal temperature of normal men and patients with varicocele before and after treatment. Int J Androl. 1993, 16: 195-200.View ArticlePubMedGoogle Scholar
- Jung A, Eberl M, Schill WB: Improvement of semen quality by nocturnal scrotal cooling and moderate behavioural change to reduce genital heat stress in men with oligoasthenoteratozoospermia. Reproduction. 2001, 121: 595-603. 10.1530/rep.0.1210595.View ArticlePubMedGoogle Scholar
- Jung A, Schill WB, Schuppe HC: Improvement of semen quality by nocturnal scrotal cooling in oligozoospermic men with a history of testicular maldescent. Int J Androl. 2005, 28: 93-98. 10.1111/j.1365-2605.2004.00517.x.View ArticlePubMedGoogle Scholar
- Waites GM: Thermoregulation of the scrotum and testis: studies in animals and significance for man. Adv Exp Med Biol. 1991, 286: 9-17.View ArticlePubMedGoogle Scholar
- Hjolland NHI, Bonde JPE, Jensen TK, Olsen J: Diurnal scrotal skin temperature and semen quality. Int J Androl. 2000, 23: 309-318. 10.1046/j.1365-2605.2000.00245.x.View ArticleGoogle Scholar
- Hjolland NHI, Storgaard L, Ernst E, Bonde JP, Olsen J: The relation between daily activities and scrotal temperature. Reprod Toxicol. 2002, 16: 209-214. 10.1016/S0890-6238(02)00026-6.View ArticleGoogle Scholar
- Jung A, Leonhardt F, Schill WB, Schuppe HC: Influence of the type of undertrousers and physical activity on scrotal temperature. Hum Reprod. 2005, 20: 1022-1027. 10.1093/humrep/deh697.View ArticlePubMedGoogle Scholar
- Bujan L, Daudin M, Charlet JP, Thonneau P, Mieusset R: Increase in scrotal temperature in car drivers. Hum Reprod. 2000, 15: 1355-1357. 10.1093/humrep/15.6.1355.View ArticlePubMedGoogle Scholar
- Thonneau P, Ducot B, Bujan L, Mieusset R, Spira A: Heat exposure as a hazard to male fertility. Lancet. 1996, 347: 204-205. 10.1016/S0140-6736(96)90391-8.View ArticlePubMedGoogle Scholar
- Chia DJ, Boston BA: Childhood obesity and the metabolic syndrome. Adv Pediatr. 2006, 53: 23-53. 10.1016/j.yapd.2006.04.005.View ArticlePubMedGoogle Scholar
- Partsch CJ, Aukamp M, Sippell WG: Scrotal temperature is increased in disposable plastic lined nappies. Arch Dis Child. 2000, 83: 364-368. 10.1136/adc.83.4.364.PubMed CentralView ArticlePubMedGoogle Scholar
- Grove GL, Grove MJ, Bates NT, Wagman LM, Leyden JJ: Scrotal temperatures do not differ among young boys wearing disposable or reusable diapers. Skin Res Technol. 2002, 8: 260-270. 10.1034/j.1600-0846.2002.00336.x.View ArticlePubMedGoogle Scholar
- Moller H: Testicular cancer risk in relation to use of disposable nappies. Arch Dis Child. 2002, 86: 28-29. 10.1136/adc.86.1.28.PubMed CentralView ArticlePubMedGoogle Scholar
- Kirchhoff C: Gene expression in the epididymis. Int Rev Cytol. 1999, 188: 133-202.View ArticlePubMedGoogle Scholar
- Pera I, Ivell R, Kirchhoff C: Body temperature (37 C) specifically downregulates the mRNA for the major sperm surface antigen CD52 in epididymal cell culture. Endocrinology. 1996, 137: 44514459-10.1210/en.137.10.4451.Google Scholar
- Sharpe RM: Pathways of endocrine disruption during male sexual differentiation and masculinisation. Best Pract Res Clin Endocrinol Metab. 2006, 20: 91-110. 10.1016/j.beem.2005.09.005.View ArticlePubMedGoogle Scholar
- Travison TG, Araujo AB, O'Donnell AB, Kupelian V, McKinlay JB: A population-level decline in serum testosterone levels in American men. J Clin Endocrinol Metab. 2007, 92: 196-202. 10.1210/jc.2006-1375.View ArticlePubMedGoogle Scholar
- Hughes IA: How vulnerable is the developing testis to the external environment?. Arch Dis Child. 2000, 83: 281-282. 10.1136/adc.83.4.281.PubMed CentralView ArticlePubMedGoogle Scholar
- Jury JA, Frayne J, Hall L: Sequence analysis of a variety of primate fertilin alpha genes: evidence for non-functional genes in the gorilla and man. Mol Reprod Dev. 1998, 51: 92-97. 10.1002/(SICI)1098-2795(199809)51:1<92::AID-MRD11>3.0.CO;2-W.View ArticlePubMedGoogle Scholar
- Ivell R, Pusch W, Balvers M, Valentin M, Walther N, Weinbauer G: Progressive inactivation of the haploid expressed gene for the sperm-specific endozepine-like peptide (ELP) through primate evolution. Gene. 2000, 255: 335-345. 10.1016/S0378-1119(00)00317-6.View ArticlePubMedGoogle Scholar
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