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Two representations of the mammalian tree showing the relationships among the orders; left-Afrotheria hypothesis, right-Atlantogenata hypothesis. Both dendrograms trace the evolutionary trajectories of four character states represented by different colours: testicondy-red, marsupial-black, descended ascrotal-yellow, descended scrotal-blue, equivocal situation-grey.
Source publication
This paper re-examines the evolution of the scrotum and testicular descent in the context of the recent phylogeny of mammals. The adaptive significance of testicular descent and scrotality is briefly discussed. We mapped four character states reflecting the position of testes and presence of scrotum onto recent mammalian phylogeny. Our results are...
Context in source publication
Context 1
... results of mapping the four character states on the present- day phylogenetic tree of mammals are diagrammatically depicted in fi gures 1 and 2. Figure 1 shows the relationships among different mammalian orders. Figure 2 focuses more closely on the situation within the clade Laurasiatheria, because this group shows a particularly high diversity in testicular position and development of the scrotum. ...
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Citations
... Testicular descent is present in more than 99% of extant mammals and is thought to have arisen due to the evolution of endothermy and the resulting temperature-induced negative effects on sperm production (Werdelin and Nilsonne, 1999;Kleisner et al., 2010). However, there are numerous eutherian mammals, namely within Afrotheria, with either partial testicular descent or internal testes (testicond), while both living species of monotremes are testicond (Sharma et al., 2018). ...
Introduction: During early development in most male mammals the testes move from a position near the kidneys through the abdomen to eventually reside in the scrotum. The transabdominal phase of this migration is driven by insulin-like peptide 3 (INSL3) which stimulates growth of the gubernaculum, a key ligament connecting the testes with the abdominal wall. While all marsupials, except the marsupial mole (Notoryctes typhlops), have a scrotum and fully descended testes, it is unclear if INSL3 drives this process in marsupials especially given that marsupials have a different mechanism of scrotum determination and position relative to the phallus compared to eutherian mammals.
Methods: To understand if INSL3 plays a role in marsupial testicular descent we have sequenced and curated the INSL3 gene and its receptor (RXFP2) in a range of marsupials representing every order. Furthermore, we looked at single cell RNA-seq and qPCR analysis of INSL3 in the fat-tailed dunnart testis (Sminthopsis crassicaudata) to understand the location and timing of expression during development.
Results: These data show a strong phylogenetic similarity between marsupial and eutherian orthologues, but not with monotreme INSL3s which were more similar to the ancestral RLN3 gene. We have also shown the genomic location of INSL3, and surrounding genes is conserved in a range of marsupials and eutherians. Single cell RNA-seq and qPCR data show that INSL3 mRNA is expressed specifically in Leydig cells and expressed at higher levels during the testicular descent phase in developing marsupials.
Discussion: Together, these data argue strongly for a therian origin of INSL3 mediated testicular descent in mammals and suggests that a coordinated movement of the testes to the abdominal wall may have preceded externalization in marsupials and therian mammals.
... Most adult male mammals have completely descended testes (CDT) from the position of primitive gonad into the scrotum (such as dogs, tigers, mice, and gorillas) (Kleisner et al., 2010;Hafez, 2012). However, some lineages of mammals have natural healthy ascrotal testes located in an intra-abdominal position or inside the inguinal region (Hutson et al., 1992). ...
... Data on the testicular positions (i.e., CDT, IDT, and UDT) of representative mammals included in the study were obtained from the literature (Williams and Hutson, 1991;Hutson et al., 1992;Foresta et al., 2008;Kleisner et al., 2010;Lovegrove, 2014) and are provided in Supplementary Table 2 Information on sperm motility, including VCL, VAP, VSL, LIN, ALH, STR, WOB, BCF, and total motility from CASA was collected from a literature search (Supplementary Table 3). ...
Cryptorchidism is the failure of one or both testes to descend into the bottom of the scrotum. This common congenital malformation in humans and domestic animals is the best characterized risk factor for abnormal sperm functions and infertility. However, current treatment approaches for cryptorchidism do not ensure paternity in all cases. Some lineages of mammals (such as elephants and cetaceans) have natural ascrotal testes (i.e., undescended or incompletely descended testes) and normal sperm motility and fertility, providing an opportunity to understand the genetic basis of cryptorchidism. In this study, we showed that genes associated with sperm motility and competition/fertility in ascrotal mammals experienced frequent, strong selective pressure. The fixation of specific amino acids and positive selection in ascrotal mammals could affect the physicochemical properties and functions of fertilization-related proteins. In a comparison between mammals with undescended testes and incompletely descended testes, discrepancies in genes showing evidence for adaptive evolution and in functional enrichment suggested that multiple molecular mechanisms contribute to the maintenance of fertility in the challenging testicular environment. Our findings revealed substantial heterogeneity in the divergence of fertilization-related genes between natural scrotal and ascrotal mammals and provide insight into molecular mechanisms underlying normal sperm motility and competition in natural ascrotal mammals. We provide a detailed theoretical basis for understanding the pathology of cryptorchidism from a molecular evolutionary perspective. This study may contribute to the establishment of diagnostic and therapeutic targets for sperm motility and fertility disorders due to congenital cryptorchidism in humans and domestic animals.
... Most species in Afrotheria-e.g. elephant (Loxodonta africana), cape golden mole (Chrysochloris asiatica), and manatee (Trichechus manatus latirostris)-have UDT [14][15][16], whereas the aardvark (Orycteropus afer afer) has incompletely descended testes (IDT) and lacks a scrotum [17]. In addition, armadillo (Dasypus novemcinctus; Xenarthra) and several lineages of Boreoeutheria (e.g. ...
... Monotremata, Afrotheria, Cingulata, Rodentia, Chiroptera, Cetartiodactyla, Pinnipedia, and Eulipotyphla. Although Kleisner et al. [15] and Lovegrove [16] suggested that the scrotal testis is a derived state in mammals, Werdelin and Nilsonne [14] and Sharma et al. [17] argue that the scrotal CDT is the ancestral state and was subsequently lost in separate lineages. Overall, our reconstruction of the evolutionary history of testicular descent and the presence of the scrotum relied on a high order-level species coverage and wellaccepted phylogeny, providing more credible information about the plesiomorphic scrotal testis in mammals. ...
Background
The mammalian testis is an important male exocrine gland and spermatozoa-producing organ that usually lies in extra-abdominal scrotums to provide a cooler environment for spermatogenesis and sperm storage. Testicles sometimes fail to descend, leading to cryptorchidism. However, certain groups of mammals possess inherently ascrotal testes (i.e. testes that do not descend completely or at all) that have the same physiological functions as completely descended scrotal testes. Although several anatomical and hormonal factors involved in testicular descent have been studied, there is still a paucity of comprehensive research on the genetic mechanisms underlying the evolution of testicular descent in mammals and how mammals with ascrotal testes maintain their reproductive health.
Results
We performed integrative phenotypic and comparative genomic analyses of 380 cryptorchidism-related genes and found that the mammalian ascrotal testes trait is derived from an ancestral scrotal state. Rapidly evolving genes in ascrotal mammals were enriched in the Hedgehog pathway—which regulates Leydig cell differentiation and testosterone secretion—and muscle development. Moreover, some cryptorchidism-related genes in ascrotal mammals had undergone positive selection and contained specific mutations and indels. Genes harboring convergent/parallel amino acid substitutions between ascrotal mammals were enriched in GTPase functions.
Conclusions
Our results suggest that the scrotal testis is an ancestral state in mammals, and the ascrotal phenotype was derived multiple times in independent lineages. In addition, the adaptive evolution of genes involved in testicular descent and the development of the gubernaculum contributed to the evolution of ascrotal testes. Accurate DNA replication, the proper segregation of genetic material, and appropriate autophagy are the potential mechanisms for maintaining physiological normality during spermatogenesis in ascrotal mammals. Furthermore, the molecular convergence of GTPases is probably a mechanism in the ascrotal testes of different mammals. This study provides novel insights into the evolution of the testis and scrotum in mammals and contributes to a better understanding of the pathogenesis of cryptorchidism in humans.
... Most mammals, such as primates, have testes located in the scrotum outside the abdominal cavity, i.e., scrotal testicular mammals [6]. For them, the testes failing to fall leads to cryptorchidism [7]. ...
During embryonic development in mammals, the testicles generally descend into the scrotum, making the testicular temperature 2–4 °C lower than the core temperature via heat exchange and clearance, and thus more beneficial for normal spermatogenesis. Failure to descend, known as cryptorchidism, carries a series of risks such as infertility and testicular cancer. However, some mammals have evolved abdominal testes while maintaining healthy reproduction. To explore the underlying molecular mechanism, we conducted comparative genomic analyses and functional assays on the spermatogenesis-related ubiquitin–proteasome system (UPS) genes essential to sperm formation in representative laurasiatherians. Here, positive selection and rapid evolution of spermatogenesis-related UPS genes were identified in the abdominal testicular laurasiatherians. Moreover, potential convergent amino acids were found between distantly related species with similar abdominal testicles and functional analyses showed RNF8 (V437I) in abdominal testicular species (437I) has a stronger ubiquitination ability, which suggests that the mammals with abdominal testes might exhibit enhanced sperm cell histone clearance to maintain sperm formation. This evidence implies that, in response to “cryptorchidism injury”, spermatogenesis-related UPS genes in the abdominal testicular species might have undergone adaptive evolution to stabilize sperm formation. Thus, our study could provide some novel insights into the reproductive adaptation in abdominal testicular mammals.
... The diversity of testicular positions is one of the most remarkable traits in mammals [1]. Most mammals develop a pair of scrotal testes descending from the embryonic kidney region into scrotal sacs, which leave the body core, while a number of other mammals have ascrotal testes still located in the body core [2]. ...
... Most mammals develop a pair of scrotal testes descending from the embryonic kidney region into scrotal sacs, which leave the body core, while a number of other mammals have ascrotal testes still located in the body core [2]. The scrotal testes exhibit complete descent (CDT), whereas ascrotal testes can be further classified into incompletely descended testes (IDT) in the inguinal region of the lower abdomen and the undescended testes (UDT) around the kidney (Fig. 1) [1,3,4]. For example, primates and most rodents carry scrotal CDT, whereas some highly specialized aquatic mammals, such as cetaceans, sirenians, and some bats, have ascrotal IDT, and monotremes and most afrotherians have UDT [2,5]. ...
... From an adaptive evolution perspective, the diverse testicular positions in different groups of mammals benefits the adaptation to their unique environments and lifestyles. For example, the ascrotal testis is accompanied with streamlined body shape in many aquatic taxa (e.g., true seals, cetaceans and manatees) [1]. Specifically, a number of hypotheses have been proposed to explain the variation in testicular position among mammals, although none fully explains the observed variation. ...
Background
Mammals have wide variations in testicular position, with scrotal testes in some species and ascrotal testes in others. Although cryptorchidism is hazardous to human health, some mammalian taxa are natural cryptorchids. However, the evolution of testicular position and the molecular mechanisms underlying the maintenance of health, including reproductive health, in ascrotal mammals are not clear.
Results
In the present study, comparative genomics and evolutionary analyses revealed that genes associated with the extracellular matrix and muscle, contributing to the development of the gubernaculum, were involved in the evolution of testicular position in mammals. Moreover, genes related to testicular position were significantly associated with spermatogenesis and sperm fertility. These genes showed rapid evolution and the signature of positive selection, with specific substitutions in ascrotal mammals. Genes associated with testicular position were significantly enriched in functions and pathways related to cancer, DNA repair, DNA replication, and autophagy.
Conclusions
Our results revealed that alterations in gubernaculum development contributed to the evolution of testicular position in mammals and provided the first support for two hypotheses for variation in testicular position in mammals, the “cooling hypothesis”, which proposes that the scrotum provides a cool environment for acutely heat-sensitive sperm and the “training hypothesis”, which proposes that the scrotum develops the sperm by exposing them to an exterior environment. Further, we identified cancer resistance and DNA repair as potential protective mechanisms in natural cryptorchids. These findings provide general insights into cryptorchidism and have implications for health and infertility both in humans and domestic mammals.
... All of the laurasiatherians species have either ascrotal testes which are partially descend in the lower abdomen, or scrotal testes locate in scrotums. Eulipotyphlans, megabats, some pinnipeds, cetaceans, and rhinoceroses are ascrotal (Kleisner et al., 2010;Lovegrove, 2014;Shoshani & McKenna, 1998;Williams & Hutson, 1991), while others like cows, horses, and dogs are scrotal (Table S1). Thus, laurasiatherians is an ideal model for understanding the mechanism of testicular descent. ...
... Based on the identification and description of scrotums and the location of testes in adult male animals, these 28 representative laurasiatherians were assigned into two phenotypic classifications: (1) the ascrotal species with incompletely descended testes, and (2) the scrotal species with completely descended testes (Hutson et al., 1992;Kleisner et al., 2010;Lovegrove, 2014;Williams & Hutson, 1991). These classifications are provided for each species in Table S1. ...
Unsuccessful descent of testes in humans and other scrotal mammals can result in cryptorchidism, consequent abnormalities and a high risk of malignancy. However, many male adult mammals possessing natural ascrotal testes are as viable and healthy as other scrotal mammals. This study performed an evolutionary analysis on the desert hedgehog (DHH) signaling pathway, an important regulator for testicular development, mainly in laurasiatherians. Significant positive selection, accelerated evolutionary rates, and specific amino acid substitutions were identified in ascrotal species, some of which caused radical changes in physicochemical and biological properties. Considering that most signs of positive selection were identified in genes responsible for or related to negative regulation, we suggest that the enhanced negative regulation of the DHH signaling pathway drives, at least in part, the evolution of ascrotal testes in laurasiatherians and other mammals. This study could provide some novel insights into the evolution of natural healthy ‘cryptorchidism’ in mammals and into the convergent molecular evolution of the complex trait.
... In contrast, in armadillos, the testes occupy a more caudal and inguinal position, some authors mentioning the presence of a short peritoneal protrusion into the inguinal canal (Rapp, 1852; Kaudern, 1914;Newfang, 1947). Intraabdominal testes occur also in most afrotherian species, Eulipotyphla, and Pholidota (Kleisner, Ivell & Flegr, 2010;Lovegrove, 2014). It is still controversial whether the undescended testes position is an ancestral condition or a derived characteristic in placental mammals. ...
... Some authors argue that a descended scrotal position of the testes evolved early in mammalian evolution, and was independently lost in several lineages (Werdelin & Nilsonne, 1999;Sharma et al., 2018;Chai et al., 2021). In contrast, Kleisner, Ivell & Flegr (2010) and Lovegrove (2014) suggest that abdominal testes represent the ancestral condition in (eutherian) mammals. However, the cited studies are either based on outdated phylogenetic data (Werdelin & Nilsonne, 1999) or assumptions concerning the location of testes in Xenarthrans that are either incorrect (testicular descent, Sharma et al., 2018) or imprecise, not considering the differences in the position of the testes in anteaters and sloths compared with armadillos (as described in: Kaudern, 1914;Rossi et al., 2012;Barretto, Amorim & Falcão, 2013). ...
Background:
The giant anteater belongs to the supraorder Xenarthra which occupies a systematically isolated position among placental mammals. The species is categorized as Vulnerable by the International Union for Conservation of Nature, and understanding its reproductive characteristics is critical for future conservation efforts.
Methods:
Gross and microscopic anatomy of the genital organs of 23 male and 21 female adult and young roadkill giant anteaters in Brazil were studied.
Results:
Male giant anteaters presented a short conical penis, intraabdominal testes, and prostate, vesicular and bulbourethral glands. A tubular remnant of the partially fused Müllerian ducts extended from the seminal colliculus through the prostate gland, continued cranially in the genital fold, bifurcated, and attached with one elongation each to the left and right epididymal corpus. The structure presented a total length of up to 10 cm and contained a yellowish liquid in its lumen. Histologically, the caudal section of this structure resembled the female vagina, the middle portion corresponded to the uterus, and the extensions showed characteristics of uterine tubes. In adult female giant anteaters, ovoid ovaries with occasional seminiferous cord-like structures were observed. The animals possessed a simple uterus, which was directly continuous with the vaginal canal. The caudal portion of the vagina had two lumina, separated by a longitudinal septum and opening into two apertures into the vaginal vestibule, cranial to the urethral opening. In the urethral and the lateral vestibular wall, glandular structures with characteristics of male prostate and bulbourethral glands, respectively, were found. The vestibule opened through a vertical vulvar cleft to the exterior. A pair of well-differentiated Wolffian ducts with a central lumen originated ventrally at the vaginal opening into the vestibule and passed in a cranial direction through the ventral vaginal and uterine wall. Each duct extended highly coiled along the ipsilateral uterine tube until the lateral pole of the ovaries where it merged with the rete ovarii.
Discussion:
The reproductive morphology of giant anteaters reveals characteristics shared with other Xenarthrans: intraabdominal testes, a simple uterus, and a double caudal vagina. The persistence of well-differentiated genital ducts of the opposite sex in both males and females, however, singles them out among other species. These structures are the results of an aberration during fetal sexual differentiation and possess secretory functions. The possibility of a pathological degeneration of these organs should be considered in reproductive medicine of the species.
Conclusion:
Knowledge of the unique reproductive characteristics of the giant anteater is essential for future reproductive management of the species. Additionally, further research on the peculiarities of the persisting genital duct structures might help to understand sexual differentiation in placental mammals in general.
... Depending on the intensity of the thermal injury, testicular parenchyma degeneration and serious damage to spermatogenesis may occur (Kleisner et al., 2010;Durairajanayagam et al., 2014;Fabio-Braga and Klein, 2018). To illustrate this, Zhang et al. (2020) subjected male C57BL/6J mice to two overheating treatments at 39 and 42 ºC, submerging the lower parts of the body (hind legs, tail, and scrotum) in a thermostatically controlled water bath for 20 min. ...
Myomorphic and hystricomorphic rodents are vital for maintaining various ecosystems around the planet. This review enables a better understanding of how these rodents respond to environmental factors and adapt to climate adversities. Innumerable factors, such as photoperiod, rainfall, and temperature, can impair or contribute to the quality of rodent reproductive parameters. Prolonged animal exposure to high ambient temperatures alters thermoregulation mechanisms and causes testicular and ovarian tissue degeneration and hormonal deregulation. Photoperiod influences the biological circannual rhythm and reproductive cycles of rodents because it strongly regulates melatonin secretion by the pineal gland, which modulates gonadotropic hormone secretion. Rainfall quantity directly regulates the abundance of fruits in an ecosystem, which modulates the reproductive seasonality of species which are most dependent on a seasonal fruit-based diet. Species with a more diversified fruit diet have smaller reproductive seasonality. As such, habitats are chosen by animals for various reasons, including the availability of food, sexual partners, intra-and inter-specific competition, and predation. This knowledge allows us to monitor and establish management plans to aid in conservation strategies for wild rodent species.
... This setup is important because mammalian sperm production is temperaturesensitive, and temperatures above 38 °C can inhibit the Afrotherian Conservation Number 16 (September 2020) 5 production of normal, healthy sperm without defects (e.g., Cowles, 1965;Short, 1997). Examples of scrotal mammals include Primates, Scandentia, Dermoptera, most Rodentia, Lagomorpha, Microchiroptera, most Carnivora, most terrestrial Artiodactyla, and Equidae (Kleisner et al., 2010). Yet about 1500 mammal species are ascrotal (lacking a scrotum), with the males' testes being located inside the body, usually in the lower abdomen (Werdelin & Nilsonne, 1999). ...
... This setup is important because mammalian sperm production is temperaturesensitive, and temperatures above 38 °C can inhibit the Afrotherian Conservation Number 16 (September 2020) 5 production of normal, healthy sperm without defects (e.g., Cowles, 1965;Short, 1997). Examples of scrotal mammals include Primates, Scandentia, Dermoptera, most Rodentia, Lagomorpha, Microchiroptera, most Carnivora, most terrestrial Artiodactyla, and Equidae (Kleisner et al., 2010). Yet about 1500 mammal species are ascrotal (lacking a scrotum), with the males' testes being located inside the body, usually in the lower abdomen (Werdelin & Nilsonne, 1999). ...
