Table Of ContentAdvances in Anatomy
Embryology and Cell Biology
Vol. 177
Editors
F. Beck, Melbourne B. Christ, Freiburg
F. Clasc(cid:1), Madrid D.E. Haines, Jackson
H.-W. Korf, Frankfurt W. Kummer, Gießen
E. Marani, Leiden R. Putz, M(cid:2)nchen
Y. Sano, Kyoto T.H. Schiebler, W(cid:2)rzburg
K. Zilles, D(cid:2)sseldorf
S.C.J. van der Putte
The Devlopment
of the Perineum in the Human
A Comprehensive Histological Study
with a Special Reference to the Role
of the Stromal Components
With46Figures
S.C.J.vanderPutte
DepartmentofPathology
UniversityMedicalCentreUtrecht
P.O.Box85500,
3508GAUtrecht,
TheNetherlands
e-mail:[email protected]
LibraryofCongressControlNumber:2004102481
ISSN0301-5556
ISBN3-540-21039-3SpringerBerlinHeidelbergNewYork
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Acknowledgements
I would like to thank the technicians of the laboratories of
histopathology and immunohistochemistry for their technical
help and wish to acknowledge in particular the contribution
of Mr. H. Sakkers, J.L. Hof, W.J.M. Hermsen, and J.A.S. van
Ginkel.
IammostgratefultoMr.D.F.vanWichenforhisgreathelpin
preparingtheillustrationsandtoMrs.I.L.vanRooijenforher
assistanceinthepreparationofthemanuscript.
I also wish to express my appreciation to my colleagues Prof.
Dr. J. Huber, Drs. G. van Noort (Streeklaboratorium Patholo-
gie, Enschede), Dr. P.G.J. Nikkels, and Dr. W.G.M. Spliet for
providing the many specimens which were essential for this
investigation.
I gratefully acknowledge the generosity of the Department of
Anatomy and Embryology of the University of Amsterdam
(Prof.Dr.W.H.Lamers),DepartmentofAnatomyandEmbry-
ology of the Leiden University Medical Centre (Prof. Dr. A.C.
Gittenberger-deGroot),DepartmentofFunctionalAnatomyof
the University Medical Centre Utrecht (Dr. R.L.A.W. Bleys),
and the Hubrecht Institute of Developmental Biology Utrecht
(Prof.Dr.R.H.A.Plasterk)forgivingmeaccesstotheircollec-
tionsofhumanembryos.
Contents
1 Introduction. . . . . . . . . . . . . . . . . . . . . . . . 1
2 MaterialsandMethods. . . . . . . . . . . . . . . . . 2
3 DevelopmentoftheSexuallyIndifferentPerineum 3
3.1 Introduction. . . . . . . . . . . . . . . . . . . . . . . . 3
3.2 Observations. . . . . . . . . . . . . . . . . . . . . . . . 4
3.2.1 PrecloacalPerineum(e.3–5mmTotalLength,
24–28DaysFertilizationAge,
CarnegieStageXI–XIII) . . . . . . . . . . . . . . . . 4
3.2.2 CloacalPerineum(e.5–15mmCRL,26–45Days
FertilizationAge,CarnegieStagesXIV–XVIII). . 5
3.2.2.1 Cloaca:EpithelialStructure . . . . . . . . . . . . . . 5
3.2.2.2 Cloaca:MesenchymalStructure . . . . . . . . . . . 11
3.2.2.3 VascularSystem. . . . . . . . . . . . . . . . . . . . . . 13
3.2.2.4 NervousSystem. . . . . . . . . . . . . . . . . . . . . . 14
3.2.2.5 ExternalPerineum. . . . . . . . . . . . . . . . . . . . 15
3.2.3 PostcloacalSexuallyIndifferentPerineum
(e.15–32mmCRL,44–56Days,
CarnegieStageXVIII–XXIII) . . . . . . . . . . . . . 17
3.2.3.1 UrogenitalSinus . . . . . . . . . . . . . . . . . . . . . 17
3.2.3.2 AnalCanal . . . . . . . . . . . . . . . . . . . . . . . . . 25
3.2.3.3 StriatedPerinealMusculature. . . . . . . . . . . . . 28
3.2.3.4 VascularSystem. . . . . . . . . . . . . . . . . . . . . . 28
3.2.3.5 NervousSystem. . . . . . . . . . . . . . . . . . . . . . 30
3.2.3.6 ExternalPerineum. . . . . . . . . . . . . . . . . . . . 30
3.3 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . 31
3.3.1 CloacalEminence . . . . . . . . . . . . . . . . . . . . 32
3.3.2 CloacaandAllantois:PartitionofMesonephric
andUretericSystems . . . . . . . . . . . . . . . . . . 32
3.3.3 DivisionoftheCloaca. . . . . . . . . . . . . . . . . . 34
3.3.4 UrogenitalSinus . . . . . . . . . . . . . . . . . . . . . 36
3.3.5 AnalCanal . . . . . . . . . . . . . . . . . . . . . . . . . 40
3.3.6 PerinealStriatedMusculature. . . . . . . . . . . . . 41
3.3.7 VascularSystem. . . . . . . . . . . . . . . . . . . . . . 42
3.3.8 LabioscrotalSwellings. . . . . . . . . . . . . . . . . . 43
X
4 DevelopmentoftheFemalePerineum . . . . . . . 43
4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . 43
4.2 Observations . . . . . . . . . . . . . . . . . . . . . . . . 44
4.2.1 Vagina . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
4.2.2 TransformationoftheUrogenitalSinusintothe
UrethraandVestibulum. . . . . . . . . . . . . . . . . 50
4.2.3 Urethra. . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
4.2.4 Vestibulum . . . . . . . . . . . . . . . . . . . . . . . . . 55
4.2.5 ErectileStructures. . . . . . . . . . . . . . . . . . . . . 57
4.2.6 FascialTissues . . . . . . . . . . . . . . . . . . . . . . . 59
4.2.7 LabiaMajora . . . . . . . . . . . . . . . . . . . . . . . . 64
4.2.8 AnalCanal . . . . . . . . . . . . . . . . . . . . . . . . . 64
4.2.9 PerinealStriatedMusculature . . . . . . . . . . . . . 67
4.2.10 ExternalPerineum . . . . . . . . . . . . . . . . . . . . 67
4.3 Discussion. . . . . . . . . . . . . . . . . . . . . . . . . . 68
4.3.1 Vagina . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
4.3.2 TransformationoftheUrogenitalSinusintothe
UrethraandVestibulum. . . . . . . . . . . . . . . . . 73
4.3.3 Urethra. . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
4.3.4 Vestibulum . . . . . . . . . . . . . . . . . . . . . . . . . 75
4.3.5 LabiaMajora . . . . . . . . . . . . . . . . . . . . . . . . 78
4.3.6 AnalCanal . . . . . . . . . . . . . . . . . . . . . . . . . 79
4.3.7 ExternalPerineum . . . . . . . . . . . . . . . . . . . . 80
5 DevelopmentoftheMalePerineum. . . . . . . . . 81
5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . 81
5.2 Observations . . . . . . . . . . . . . . . . . . . . . . . . 82
5.2.1 Urethra. . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
5.2.1.1 ProstaticUrethra . . . . . . . . . . . . . . . . . . . . . 83
5.2.1.2 MembranousUrethra . . . . . . . . . . . . . . . . . . 88
5.2.1.3 SpongyUrethra . . . . . . . . . . . . . . . . . . . . . . 89
5.2.1.4 NavicularFossa . . . . . . . . . . . . . . . . . . . . . . 91
5.2.2 ErectileStructures. . . . . . . . . . . . . . . . . . . . . 94
5.2.3 FascialTissues . . . . . . . . . . . . . . . . . . . . . . . 97
5.2.4 PerinealRaphe,Septum,Body,andFasciae . . . . 99
5.2.5 Scrotum . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
5.2.6 Penis,Prepuce,PreputialSacandFrenulum. . . . 104
5.2.7 AnalCanal . . . . . . . . . . . . . . . . . . . . . . . . . 107
5.2.8 PerinealStriatedMusculature . . . . . . . . . . . . . 107
5.2.9 ExternalPerineum . . . . . . . . . . . . . . . . . . . . 108
5.3 Discussion. . . . . . . . . . . . . . . . . . . . . . . . . . 109
5.3.1 Urethra. . . . . . . . . . . . . . . . . . . . . . . . . . . . 109
5.3.2 ErectileStructures. . . . . . . . . . . . . . . . . . . . . 113
5.3.3 PerinealRaphe,Septum,Body,andFasciae . . . . 114
5.3.4 Penis,Prepuce,PreputialSac,andFrenulum . . . 116
5.3.5 Scrotum . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
XI
6 Summary. . . . . . . . . . . . . . . . . . . . . . . . . . 118
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
SubjectIndex. . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
1
Introduction
Thedevelopmentalstepswhichleadtotheformationofthehumanperineum
seemfirmlyestablished(Arey1965;HamiltonandMossman1972;Mooreand
Persaud 1998; Wartenberg 1993; Sadler 1995; Larsen 1997). They form the
base for the evaluation of the pathogenesis of a great variety of complicated
and often serious malformations which occur in this region. This concept
has, however,beenchallengedby the resultsofaninvestigation intothenor-
mal and abnormal development of the anorectum in pig (van der Putte and
Neeteson 1983, 1984; van der Putte 1986). Observations revealedthat at least
in pig, a major element in current ideas about the early development of the
perineum, namely the process by which the original simple cloaca is subdi-
vided into a urogenital and anal part is incorrect, while additional observa-
tions strongly suggested that the same may be true for ideas about female
and male sexual transformation. A preliminary investigation in human em-
bryos gave similar indications (van derPutte 1986).The data supported ear-
lier critical findings (Politzer 1931, 1932; Wijnen 1964; Ludwig 1965) which
have apparently been ignored, possibly because they seemed to hinder the
understanding of the pathogenesis of congenital malformations such as im-
perforate anus and hypospadias. The necessity to provide an embryological
basefortheexplanationofthesemalformationshashadaprofoundeffecton
prevalent theories about the development of the anogenital region and has
evenledtotheoreticalconstructionswhichwereapparentlynotbasedonob-
servationsinembryos(Billand Johnson1958;Duhamel etal.1966;Stephens
et al. 1988, 1996). The unexpected results from an investigation into heredi-
tary congenital anorectal malformations of pig embryos have demonstrated
the weakness of such interpretations and constructions (van der Putte and
Neeteson 1984) and underlined the need for a new inquiry into the normal
developmentof theareainhuman embryos. Theseresultsdemonstratedthat
although data from malformations may offer extra information about the
normal development of the area, great care has to be taken in using that in-
formationforthereconstructionofitsnormaldevelopment,whichshouldbe
firmly based on the observation of the evolving microscopic anatomy of the
region inthe first place. However, inthis respect original workonthe devel-
opment of the perineum gave a confusing picture of fragmentary and often
conflicting information. It underlined the necessity that in case a new inves-
tigation was undertaken such a study should be comprehensive by address-
ing the whole developmental process, including not only the sexually indif-
ferentperiod andfemale andmaledifferentiation,butalso ananalysisof the
untilnowalmostcompletelyneglectedstromaltissues.
Description:For over a century, the development of the perineum has received ample attention because of the striking complexity of its formation and malformation. In the prolonged disputes at this subject, normal and abnormal development became intricately interwoven and ideas about the normal process were ofte