J.E. Jirasek

M<tho<lof", A.....
'o. It..
Elf"" ..
orCb=hIo onR..,rod-run,;
£<1,,«1b)' V. a.Vook .'" P, J Slo«,," n
C 19lIl $C OP~
F. """"""
Methods fo r Evaluat ing and Predicting
H uman Fetal Develop ment
J E. Jnu.su
I. I:-;TROD UCfION
Whenewr a pregnant wOman i' e~posed to infecliou, "gents. ionizing rad iation
or chemical'. including dru g,. lhere i' alwa)\ a possibiluy that sucb e,posu r...
may b,,-. ad"erse effects on lhe de'-elopment of the fetu s, A tberapy lhal may he
of greal benefit to lhe sic~ mother . may be al lhe same time hazardou' \Q lhe
fetus,
A terat ogen ma y be defined as a phYSIcal. chemICal Or biological agem
prod ucing ' truc tural or funclional abnor malilies in an organi, m e, posed to it
before biMh, The sensilivit)' of lhe concep tu, to an e,o genously ind ""ed damage
varies widelydepending on lhe 'la ge of developmem (Wilson. 1972).At lhe earl)'
, tage of onlogenw" berore blastogenesisi, completed (in human' during lhe first
lhree weeksafter concep tion) tbe conceptu" ife, posed 10a no.i ouug ent such a,
ionizing radiahon . lends to ha'e an "a ll-or-none" response (R u, sel and RUSst l.
1954). The embryo survives withoul an)' analomlcol damage. or dies and i.
a bon ed. During organogenesi,. approximatel)' 4- 12 weeks after concep lion. the
",n,iti" ity of embr)'o 10 morpho lollic malforma tion' is hIgh, the peak of
sensilivily beinll durinll the fifth and si~lh wee ~ a her conception_The p"riod of
p"a~ sensitl"lty '0 teratogen, includes tbe conslitu\lon of embr)"ocborionic
circulation and early differenliation of maoy orgao,. There are "c,;tiota]periods"
m morphogenesis of all ' trUCture. (Schwalbe, 1906: Sne n and Rapo la, 1%9),
Ad' er.. influences at critical p"nods rna)' invoh-e not only morpholo gic
malformal ions. bUIrna)' resull in ad'er .. changes of postoa tal functions as ,,'ell
Possible teratollens are lested usinll .. "eral species of an,mal•. In ,pite of
s,m,la"l ie, in lhe de' elopmema l pall ern, the ~uliarities of some ,~ie, ma~e
the compariso ns e' lremely difficult, For inSlan« , io"ersion of lhe germ-laye.. in
m,ce and "'IS and tbe resultinll tempo rary yolk sac placenta does nOI occur in
oth er mammal~. AIle>the metabolism of chemical, in the maternal organi,m may
differ 'ignifican tl}' belween .~ies,
n bk 1 CoInpu>ou "" c......
IIea,"'"
of pI'C1Ul
tol d, "lot.... ", of Q....
H ....
('01"1""' ''' ••
,.ge<
•••
_.
Um<cllul",
10
_
,
....
II ... ..,...., ", Cl6
,
,
lliw. .... ~ au.,.
--,
~
==do')'
T riIr._
...-
•
•,
plio..
•,
yoIL..,
", mu,
d4 }'1
ua
"'
.. ..
"' "
.......
k
w" h . """'X1oonIa1 pru<cM
l .. rl1 ...... " .. ... p)<
co nlpl<' dy ope n ,",,,' .' ."~"..
D<\l",I'n"" dOli" ..
bot h tn<li opco
'" dol'"
...." I' h
on",m
." ,
•
m ",no
,-,
O. IS
u -o.J
"
in do ys
Le
n". "
d.,..
"
~,
.,
lOll
In
l ~- n
0 2.0
,,~
"
"
"
1 S 2.0
~,
I S 40
t
e,
t
.•
.'" ..
•
<
,
..,
"•,
i
t
,
~
10
U
~
1
, , •,
0 2 ..
... bryo .....
_~ pnmI .....
mm
In
... .,
•.,
"
l-"" 8th
"
m
~,
M ""~.y
n
l.<:n. 'h
--
"' pcd ~""
.,
.-.
.,
11 . 9
"
."
'.'
"
••
U
11
"
1~
U - Hl
1(>-10 J 4
,
•
•!
,
0"" or both "o aml'<""'"
o~
S' . II' of limh <I",dopmenl
bud of pro" "," 1"" "",, " y
b oo. of pm, m.. l. oJ
d lS.. 1e"rom" j..
p ' o, ;,,, . l o, ' ,,,," ,' y
',,"oscg""'n"
1" """ ", I . oJ <1;".1 e"" " ,,, ;'y
'''-0 "<8"'"""
,I 'g". 1' . y' . [0'>1 pb' <>
"'l!<,
1'",.1 p<tiod
l'orinal . 1 r><'iod
, z ,-.
,, ,
'"
u
,", "
,. '""
"
•, " "
19-24
d ,WlS. loe luocre les
" " n8 eyel.. ,
..
r s
l J 21
d ,gu . 1' a ocrde .
La« "mbryon.1
<I,'l<re" h. I",1 "''''m,'
"'
,,
",,,
.-, -n "
• "'W,00
to
'00
"<
4.0 6,0 14 26
2& 32
sc
"
1 4.1
'"
"
"
rs
,
,
"
I
.' "•
,
'J
,
W
,
0
"
""
s.o
J7 42
"rc
n
"« "
"
H
J9 44
'00
,~ .
H
IU
SS&
"" "
sa •
"
.W
W
1&2 +
"
~
"
"
"
«
sa
1'"",.
1'"",.
nalol
1I. ~
"
" "
" "
1
"" "
17
"
19:
as
19 2 1
I'os, -
"
IJI
'" "" I
u.s
M
oa, . 1
"
"<
,,,m
~.
9. ~
'"
"
"
n
""
25
" '"
,.
•
•~
~.
,
i
..
>
,
~
~
a
a
nalal
"
302
M ~11ttHh
1MA~Jsi1lJ ,Iv
Eff r<:/J of Clvmi€au "" k p ro<JoM!
ri'rt FrmcrjqN
The a.. 1of leraloaen"my 1'"'1' .. 10 detmnine Ihe doK ,,'hich .. embr)Olo .ie
in animals ~ausin. intrautmne dealh Or 1TO"'tJ,r.urd ation. Of .. hic:h is
1.....I"l!en"'. P,odUClIlI -.nalomal malfOnTlauons..lbe mechalUsm of Ibma~ "
ftOloflCn in~aupled General m«IlaBlsm5 of mlerferm "'th prenalal I'mull
.....,1Oll rd.,fd 10 .lln-fd
aDd d,ll"cr-muauoa mr:l..... mhlbtuon of ~U prOW"
.ynih=J of protClas.. carbob)'dral" and tipids. or 10 limlled CDCl"I)' .uppl);
mhibiuon of pl:lalllallnilSfn- .nd pto .. m O)"ftUlnu, ,nlerf~ "'"h ftlal and
fetopl:locmtal ~lJOfl; and ahcred Of mluhued formalJOfl ()( _mOt}'
,,,,,,,,,,,-
lbe I}-P<"
of .... lformauon .. <daled 10 lbe otqe II ... hJdl nnbt)'O" e~ 10
a , ..... ,osa> For mtUlntt"
CoocepIUa ahOf.. d dUM . ,tard FalaUOlllI
mouth aI\cr up""'~ 10
(a folic tcid ............ ) """"' ·ed uopho.
bWtic 1XICI'OIi
.. illrombolos of lilt inlft'YilJouo opaooand damqcd (etal bemaIopooaIS
""11Lul 1M b'n- (Sha",. 1'1"'2,. If lbe (etus "'''''ed.
a Il~1
amn'opla'lfl J)'Ddromo ...". eharxlenled
b;. mall"onnalJOn' ,n 1M c",,,ral
I>C'I\ .......
}~nn. CfllUof_1
d)"19Ia.<d..dublw>ds and duhfm .• nd menul
m .r<1auon("Ttuef1ch. 19~2, H "", vd and Roo d. 19n).
lbe d1"eeu of Ihc chcmlcals ...hieh ha'"e been lesled may be claaslfied as
expeeled aDd UIlCXpecled The expeclcd effects are ....oss mall'ormallOo,.
from ' ohl btlion of grO\nh obs<n«l.On- .doun'JallOruon and cld4 .......11'0.
lrali oo of .ouoop,mn. lnlSlllf.n. chloram hucil. C)d ol'hospllaoude .nd 10100·
p<ClJIIlIC}" (Scbill"Cl. 1.. 1970). Gr o" 'lb rctardauon
""m lll ,o 1M finl Inmeilnrna} ", oull from 1M lrea lmen! " 'Ih ccmsone (Wa ITeI and Ta )'lor, 19( 8).
Mascuhnll.ll !lon of female feluses i. ao expecled conscqu~ncc adm,nll'r. ' io n
of llIdroaenic subst.nces luch IlICSIOSlerone and ;l>der;"al;" ,", (G lUmbae b and
Doc har me. 1%0). The ,nlerf.....,nce of dielh) l1lilbclIfOI (Herbal el al . 1971) wilh
no rma l 'CS.......ion of panllllClOnepbric ep ilheliu m ,..ilh,n Ihe " all,na l pLOIe
leadioilio ' ·allina l .<lenom I bo uld be con~idercd al a predic lable e/fecl S,nce
""JIM i•• kno"' n larS"1 of cslrOilen•. Telracyc hn il kno" 10 form eM Llies " il h
cabum. aod afler applicalJon 10 prep nl ,,'om en il i. deposiled in Ihe fCial baM
nuo cnll and deciduO\Isleeth (T no/Jand Ra ,.,d. 19( 8), A Ins expeclfd effecl'S 1M
deposHlon oflelr&C)'Clme,nlO 1M leo ... lcadrna 10Clla,-.:u( Harley CIII,. 196<1)
LDdcn landa hk .. 1M C'lvuh n..,...-edama ,e rd :ll od 10 MOIll)'CUI. lIrq>lom)'Cin
a nd qUI",,'" and Ihe formallon O((CUI,OH..,. Ifln- "dmuu.strallon of anu·th) 'TOld
dlUp du rinJ prqTWlO)
L;Mxp«ted 1..... 1OJmIC ctrncuare 1M dI"<CI." hJdlarcdll6culllo predlCl ~'~
if lbe metahobm
lbe cMmocal ISk_ n. Fo.- ,mtaDl%. lilt pheDoc:op) o(!be
RIppled eprp!l)_ 'lndrome (0.- cItondJ'odl'PlnIa l'~U) ""h"'b de\elopl
If"" adm.oo<lrallOfl of dlClllllll'Olloticw.alllan .. (mch III ...vfaml ) dUJ'UII11w
liN lluu monlhs" dlfticub 10 pre<hct(Shall! aDd Ha n. 19n ), Slmllarl). lbe
propcrucs of thalidon>odedo not r"",,, "Illl ibc cbara<ur
the _ ...'Cll-k_ 'n
S)ndrome t:""xp«tN elfeeu ma)" be so-..ma dercet od in I.lUmalupmmn>lI .
H.... "''CI.il should a/'tt.'I)' be unc\cnl:oodthaI alrapolalion of .uumal e<pen'
""", u ,0 IDIl:I 1:1, .. lId ... 1) 10 a hmlled dcptt
or
or
°
or
or
M"'Wlb!Qr F;,'alualmg Il1IdPredkling Human Fetal De.. lopmem
303
T~rat<>lo&"'s and exptllmenw, 1 emb!)'ologisls ha"e pro'ided much infor·
malion on the develop menta l mechanisms and their d,sturbances in d iff~ .. nt
verteb ra'es . To make lhe interprelation of "SUllS ea,ier , we ha, -e proposed a
comparal i"e c1assificalion of pronalal developm en, of qua nd",ped. in which
corre.pond ing stages a re ""'rked by lhe same s}'stem of numbers. The prena ,al
deve lopment of man. macaceus. ra, and mou... " compared in Table I.
2 M OTH ER· FETUS 1.1'0 Fl:T U5-M OTH ER TRA1'o'
SFl:R ;
THE PLACE"'T AL BARRIER
T he transfer of sub stances from the maternal in,o ,he fetal compartment takes
pla"" either across ' he placenta Or across fela l membranes . Only under
therapeut ical Of e, perimenta l condi'ions ,ub stances aT<adminislered dire<;tly
in,o 'he amn ion. or into 'he peritonea l cavity of 'he felUs (in,rau tenne fetal
trans fusion ), Transpo n mechanism' are related '0 the anawmy of 'he biological
barrier. t<>lhe uterochOfionic and uteropla""n,a l (materna l) circula,io n and to
the embr;o-chorionic or feto_placental (fe'al) circula lion ,
The 10lalmalerna l ulerine blood flowis considero;l to be 94-1 ml mmute kg
at 10-28 gesta,iona l weeks a nd approxlma,ely 150ml minute kg at the term
(Assah et a1.. 1%0 ). The blood flow enter ing in'en'illous space ISintermitlen t.
and 'he blood pres sure in the terminal uterine arteries is 70-80 mmHg (Alvare:>:
and Ca ld";ro- Bareia. 1950). The blood pressure In lhc int.".il lous space i'
approxima tely lOmmHg. and increa... s duri ng uterine conlra C"on, up to 30-50
mmHg, Th e pressure in 'he maternal veIn, leaving 'he inters'inous space .. about
8 mmHg. Th e blood pressure "ithin 'he in,ervillous space i' lo"er than thai
"i'h in the chorionic (fetal) vessels. The blood pressure in the umb>hcalaner ies i.
approxImate ly 48-5OmmH g and in Ihe "ein 24 mmHg (J>largolis and Orcu tl.
1960), Th e.. cond itions faVOffe'o_materna l tr an. port ,
The paraplacental transfer is effec'ed by a Iranspon from decidual ""lis across
'he chorion into Ihe amnion For in"anco. prolac tine roleased from decidua lcoUs
crosses thec horion and amnion and dIffusesinto 'he amnionic fluid (Riddick and
Masler. 19&1).The ,ra n,pen of decidual pro lactine requi .... act ive pro,ein
synthesis and an intact microlUbular sY"em. Th e permeab ,llty of amnioc horion
can be ea, il; siudied in vilro (Seed, el aI., 1980),
The placenlal transfer tak .. place by diffu,ion , b; facihtaled diffusion, by
aCll"e transport (against 'he grad ient). by endoc)"oSl'. Or b}' other poorly
unders'ood mechanisms. and depends on ' he ph)" icochemical properties of
chemicals. such a. molecular w .. ght. ioniza'ion, hpld SOlubility and prot.. n
binding (Mir kin. 1976)
Compounds wilh low molecular "eillh' diffuse more rapidly, If the molecular
weigh, exceed. I000u. ' he passage a'"os, 'he placen,a i. usuallyslow, Mo lecules
in non-ionized sta,e eros. 'h e placental barrier mote rapid ly 'han in ionized Slate.
li pid solubility facilities the'ransper! . There i, a substantial difference be,ween
protein b>nding in 'he ma,erna l and fetal blood plasma, Thi' differencernaye.ert
n
304
M n llodsj or Asstssing IIu>Effects of Chem ical.<<m Rqmdwcli'"I' FW1C1iorts
a signIficant mOuenceon lhe transfer of chemical•. especially if the fr"" subslance
the placenlal ba,, ';el slowly. There are $Ornespecific placentaltran.rer
crOS5.eS
,} stems invol" ng ,pec ificconjugation of tho suMtanc ocr""ing tho plaeonta to a
co mplex which i' cl<:and befon: lhe substa nce is reka>e<l after the transport
acr"" lhe trophobla,t.
The placenta . .. pecially lhe trophob lasl. conta in. ellZyme, metabo lizing
endogenous a, "'onas xmob iotic ,u b'trat .. (Hagerma n. 19(9). Somoof them are
of fundamenta l ph}',iological impo n ance. for e"" mpl<:.t be monoamin e oxida ..
(De Maria . 19(3) wh'ch deaminatesa number of , uMtr ates,uch as epmephrlne.
norepinephrine , dopa mine... rOlonine a nd some amp helamines : diamine oxi_
dase (hi'lamin a .. ) (Weingold and Southern.
19(8); catecho l-Omethyllran,f era"" which lnact,,-at« epmephn ne and norepInephri ne; """e", l
per tlda .. ,. 'ucb a, cystine aminopepl ida.. (ox}'tocin.... ) (Mathur and Wa lker.
19N1: choline acelytran, fera.", (Bull "' at.. 1%1); 3/i.bydroxy"","oid dohy_
drogena... 11/l-h}'droxYSleroiddehyd rogenase. a very potont steroid arylat ing
s}' tom. a nd othe" .
The elfe<:t' of cbomlCal' on the placontal "ascu la,uro can bc SludlM 10vi"o in
ptlfu sion experimem (Mancini and Gaut ie" 1%4 ). Serotonin. norepinephrine.
LSD and some oth er ballucinogen,. morphine and codeine are poten, con_
strictors of placenla l ,·«",,1,. at lea' t 10 ' -'lro (Ganl a nd D yer. 1971),
Prostagland in F, . enhances the effect of oxytocin (Jung mannova er al,. 1975).
It i' evident tha t placOIllalon,ymatlc S}'St
,mHan meta boli' e a large numbcr of
endoge nous as well a, e"' geno,," substanc... Hyd rolyzable ,ubstrat .. are
u,ually hydro lyzed. and ,,,soa cti, .. ,uMtances and hormonal pept ides aro
metabolized 10 maCti' " SUM'anc<:$, Placenta l conjugati ons. wilh a po" ible
excepuon of acetylation. seem not to occur,
3 PRENATAL DETECT ION OF FETAL MALFO RMATl O,""SA" D
CHRO;\10SO :\-IALAND GENETIC DISEASES
Te<:hnique. uSC<!for prena,a l detoxuon of fetal disorders can be c1a"i fied a,
invam 'e and non-in".,i' -e In, ,, , ive technique•. , uch a, amnloc,nthem and
fet<»copy. include p"' etrat ion onto ' he amn lo, ic cavity. Non-,nyasiw te<:hniqu..
are based On X_ra, or ul'raso und procedure, . or on different kond' of felal
monltoring.
3. 1. !",,,,,""urO'SBa"'" "" Amni""emh....
Am niocOIlthe'i' is u,ua ll}'performed at 16 18 w""ks of g.. tation . The 'o lume of
amnio' ic ftuid at thi' . tage is appro, imatel; 120-3lXlmi. from " hich 5-20 ml aro
" ithdra wn and used for ana ly'is . The risk of COmpliC
atio n, " laled to amniocenthe,i, i. Ie.. that 0.5 \ (S,rnpSon and Mart in. 1976). Pot, nllal mat erna l
comp licatio n, Include Intra -abdominal bleeding. punc ture of the bladder or
Method ./or £.'oluolingand PrMicring HumtJ!I FeIOI De>'ewpmenl
ont~'t ine
'"
and Rh·immunl2al ion. Pos, ible f~lal compl ication, are injune , 10 'he
felu. b) lhe nffi:lle, bleeding from placen'al ves,. l•. InIt.ovular ,nfecuon a nd
a bon ion, Leakage of amnIotICfluId ha. also been repon ed,
Th~ amnim ic flu,d sample is c~ntrifuged, and lhe celh are used for cylolog ic
e ~a m on a ,i on. CUllivaIion and , ubsequ ~ nt chromo'o mal and melabo lic analy.i "
The fluid can ~ examined by biochemical melhod "
3 ,/./
Cyl olog)' 0/ Amnioli c Cel/,
Centr ifuged cells from ammol ic fluid are spr~ad on a microscopic slide. fixed in
formatin in "apor and, if an ope n neural l u~ defect i' ' U$p<Cted , th~ ,mear ,.
checked for lhe presence of glial elemems (Brock. 1978). The glial elemenl' are
l:" pola r. elongaled an d Mtectabl~ by a glial protein S-loo e~h; bil ing a sp<Clfk
immunofluorescence (Sarkar cr al.. 1980). Ana lysis for X< hromat m and y.
ChrOmal in in uncultivaled amn;ol ic c~ll, can ~ ea,i ly perforrne<l; however. the
r.. uh' are far Ie" informaliye than karY01YPing
3.1.1 Amn iotic Cell, Ti5sue CullUre.
Cen,,, fuged cell' from amn iolic fluid are culliy'aled for apprmtima lely 2-4 weeks
in a nUlrient medium con,aln ing ca lf serum and anub,olIC•. Tbe c ul,;,·allon,.
. u,,"es, ful in 70--99';. of ca ses, 1f karY01yping i' required. colchicine i. added 10
the growin g cullure (mlloses are a,re ,led al metapha,.). the medium of the
culture i, h)'po tonized and acellc acld·m<'1hanol fixalive added: cells ar~ , pread
on microscopic slid.. and 'l ained b) different banding techniques, Using th is
melhod a ll numerical chromosomal abnormallues Can be detecled. Th~ most
comm on l\ lhe mono,om y for lhe X..chromosome (45.X). Th~ Olher qu;t~
frequently occurring palho loglc hr;o types are 47.XXY: 47.XXX: 47. + 21:
4 7. + 18, 47. _ 13,
The dete.;uon of , truCIUr. 1chromO>Qmal anomalies depend. on Ihe extent of
chromosomal leSIOns,MInor abnormalities may remam undetected. Struclural
chromosoma l abnormalit l<:<l o , o l , ~ de lelions. lran, locallon, and rearran ge·
menls r.. ulting in lhe forma lion of iwc hromo' ome' . Incomplete chromosomes.
fr~ g menl' , n ng<hromo,ome , . "'c. Chromosomal break ' are o~r",,<1 afler Xra} irradiation.
The mo,t impo rta nt indicau on for prenala l karyoty pinll of the fem, are
chromow mal abnormalilies (such as ba lanced lran slocalion Or im'ersio" ) in
either p;lrent , advanced matern a l age or existence of indi,'idua ls affected by
chro mosomal an euploid;. or anOlher chromosomal abnormali ty in llie famil},
Cu ltur.. from amniolic fluid of fem, .. Wilh 0P"" neura llu\>e defects comain
glial c~ ll, " hich are elonga ,ed. b;· polar and exceptionall} adh.. ; , ~ (rapid
adher ent (}f RA cells). and com ain a specific gha l pro le;n (Sarkar et al .. 1980) ,
C ulture s of amn iotic cell, can also ~ u<ed 10detecl man; metabolic diseases
w;lh known biochemical ba sis. The biochemical defecl i, usua lly idenlified b)'
M tl /todsj <>rA3HJJUtsI1wEjJ«u "jC!wmkal> .... R~p'<><hKllw Fu>lCI
......
306
em) ...... a..,..ys ,n cullum! ullt. Abnut 73 dJlfcrnll mrubo(;c dlSOl"dfrl(such as
mucopolysa<bandoses. 11~05eS. ~podmes. ammOK>dopatlua.
nO'" be diaJllosed pmlataJIy (Golbu$ ~'"L 1976; Rill".,. 1976).
1lIQcloDorinoJ
A"')~"
J.IJ
<>f
A_ir
etc ) aon
Flvid
(a ] A/pIIt>-fr'..,..nM AF'
A FP II lyutbcsizcd '" fcul cododn"ma l.u,ICtUfn
lOCh as the ),,11<Me. hn alMlCU" AF P \11ll1llDi<Mic
l!IOO"'"IU"'ta
pIOl:Iably
from r~l u.ntIC. and ,I' allllllOUC ~UJ,lIOCI <lcaa .... "'tb ad'"lIl1CU1J
~tionaI. (Broc k aDd Sutduft"c, 1972) EIc>"lItcd a:w;:ultnollOllS 0( AFP .,.,
mtOUnlercd in opm """,*1 tube M<xu (..... lXephaly. opeD spmabltlda j aDd
ba'''' also been IepCI<ttd'" MeIOCO<X)P teraloma. ompbalncdo aDdcoapmw
neplu""",, aDd ID ptep'aTlCM'$ .. "II rnal death>: elc>lItcd AFP IS somet>_
~t abo m fet....... ,Ib amsaas '" dJF'U'" lUbe. polycyst", bd.Df)'$. UUlulal
pancreu. h)-.lrocepbalus. fallot·.teuaJoc aDd <:<>n&=1a1....'D defocu . ~ ormal
<:onCeIlUJ,uons0( amDIOllC A FP dunn l ~[lOl>al ..«k . 16-1& are bet .. '","" 20
aDd 7DLmL In f.. uses ",Ih opm neul"llilube defeeu. the AFP 'lIl\1f$ eXffd
25l1J. rea<:tulll in some cases «Xl- ~nl. ml ( Broc k. 197&). ContamlnatlQll 01"
tht amni otic lIwd ..,,11 fnal blond is tbe most common $Oultt oI"fabe poIll""i:
['filiiI'.
(b) HOI'_
' in "",n"'li<" jfuid. F... I K~ CIIn be pm!"' tcd fr om tbe ammOI'"
CC<lCefI
mlli oo of tnlOStcron e. FS H an d L H. In male fetuses. tntOllcron e
oo~nl ra\lon ,$ much h,. be r. • nd FSH In d LH COllC01l
lra lion 10,,"'''' IMn in
r.male,
The dilferenc .. m amnio lic concentra lions of testOllOro ne. FSH I nd LH
d unn g gesta lional .... kl 16- 18 a", , ho" n in Ta ble 2
EStlmal ion of am mollC concentratio n of FSH and 3. 3'. SAri od othyron,ne
( RT. ) could be useful for prenatal d la", ,,, .. or fetal hypotbe yroldism , .'Ih .r
con goni,. 1or induced by .~posu '" of pl'eJU nl "'OIDOll to I lrumi .. n$ (Chopra
and Cl"lIOOa
ll, 1975). EIo' '&led am nIot ic 17-hydro~)'prOilnl"'OIle "' &I observed
in f011LSC1
alf.." ed by .drmal (or tlCal hyporpla.i. duo 10 C-2l Slnoid hy·
dro~yw.. dooo ency (PooIII01 al.. 1980).
,- Tablo 2
DIlI"om><n III boo_
__
lAo
Ie-IS
_dunq
_~-....
T
FSH
LH
"",,, 10 in tbe fCl.ll ._
.....
.,ld
M.
"' ........ aDd
l ao-- I:~C~"'~"'----c",,,,-,,-----2O-JO",,'"
OOS-O,12 .......
:1--1.......
O.l---.(l
.7
9-U
.
1DI
.v~,ltoJsjQ,
).2
F~lIl1lNti~ID"mn"
£".,/lIa'I1I6"" PMik tu., H_
)07
FcI OlCOp)'
Duo;t ",... 1 ~lXIIl of the f~lus ISpnfonroed b) a fet"'""P" . a speaa l
liberopl><:eodOlCOpt. Ahhou&b
SInlul~ 'UI.lalin."""
ol !he ... un fC'lU$IS
l>l>t poosiblt.lSOlaled portiofts oltbe fC'l
ut sudI all OClIJp
. e,.-cs.1ipa.
fiD&en.
lacs.
ulmlal Jftlltalaa aDd tho anI....,. bod y .... mclucha,!he lDXt"tioa oflllllbllg l
cord. ma y M chlo;tly CDmu>«l III _
~!he " ... IizaUOll ol. SlnIC1un:
.
"boK Illalom y 1$ 10 M cum" .. d lilly M ''ftY dJffic:uItbccaUIC ol !he
COllt.lllUllllXlll ollmm<IUClIuid eitber b) lllO::OO'wtl Of byblood . l a ow 1KIlp1l1
fC'lOKop)'ISpnfonroedl11ldtt grnln l anesltwsr.a. Tbc \lo' olf fC'lOlCOpt
() . 2 mm
diamn ....' ISInocned inlo lhe:ul..,.". und...-,,""I COIltrOI afttt a .mallla""rOlom)
has bea1 perfonroed; a .utu n: i. It' led Ir cuDd the fC'l""""PC iaxnlOCl Tbc
IocalizauOCl of tM pla«n ta is al }'S ckl....mlned ulu-l.SonnUy .Dd Iht
InlnsplaCClltalroute of f..."""opt lnw rllon i. stnctly avoided , Th~ n sl of felal
death a nd .bon lOCla fter feloocopy i. approxtn\lt~ly Zlr" , Abo rtion. art n:1ated
10 Ieax"it of . mniotic lIuid and . ubSl'q u ~n t . mnioxhorion lti<.-r.r~ l y 10 Intra·
amniotICblecdini. Chronic Ie.kail~ of . mnlOlle fluid durini the:third tri mtst~r
requi res I Ioni· t....m hOSpita lization in I ppr oxlmattl ) 3'r" of patltntS.
F...os<:"PY.110..... prtna ta l dll iOOSIS of IU major u, ema l morpholoaiQIl
malformaliOCluuch IS facillcJeft •. deformed u tenll ln .... defo;t. of CNS.1fOSS
malfOrnllllOCl' of hmbs (phocomelsa. an~). oliaodactybes . pot)"dac.
I)'~cs. . }udal:lyMa, clef..,.. ofantmOf
body ... U ....d SO"'l' malfOfmlltlOCl'of
n.
""tml l sm>lIha.
FC'loocopy " lIidnted
'" .}"DdrollJCl.. hodl do DOlexhibit cllromoloml l Of
arid "'iucb an:
eharaclcriml by comtIa'lllalom
l malfOl'1l\lUOOl
DiIJDo:>RIC
fetotCOJlyhas lxnI pnfOfllWd In O\lf bosplll l by Z..1qft" In 41
cases . 2Oofthem ..'"" tbmr.peutiICIlly abort ed Malforma tions ..ut found '" 18
easel . In 1"'0 cascs '" .. lucb 1M fel\UOeS
.. ut dl&poscd fOlOlCopa l!) IS
malfOl'D>ed
. 1M<hIiO........... not confirmedafter aboru"'" t:" ......ted abomon
occurr<d '" four pallallS "" tb lI<:aJ
'hy fC'luSts. Pte-ttrm <k~,~ OIXUfTedIII
tbJcc cases. 1"'0 Jlfe-ltnII ,,", 'born. dted, T..-enly plluen.. de~,'Cfed b<:allby
cluldrm II fuJl·I£nO. leabgt ol.mnlOlIC ftuKl~ in six ol them . US'n,
fetoscopc " 'e d~tecl ed follo..in i defec,- : fanubll elefl.ltp I nd pa late (6 caSts).
Treach..,. Colhn.· Iyndrome (2 caws). anencephaly (pn:>-;ou s!y dll in OSl'<!
uh rason iQIily. 2 cases). ectr odactyly (I case). Sald,no-Noona n .yndrom~ (I
caw). MaJe" ',x l,yn drome (I caw). I}'ndac,yly Iype V( 1case). Robert' .yndrome
(I CI.Ie). a n hr08ryposi, (I ca st). Aperl Iynd rome (l ea<el, Lip piH:len ltp
I)ndrome ( I casel,
&mpl"" offrl~1
ftl~~i(: roniTo/ Tbe n«dJe.cope . .. hlChhall
ralher bnuted VISualkid for. gtn .... 1fetOKOpy;, a ioodtool fOfVlSualiution
of cbononic ,-eon' In tM placen1l1 plate , Ann . ,uillblt "em is >UWl1~ . •
hcpannt«d ~It " dlt'CC
<edinlO the lumen ol the ''tUd, 8 ) du....... bod 1"''''
biocMm l.boorma~l>CS mbcnted ~ 10MCftdeIwo Io....'$.
,u.s..,
""tk,
308
Melhods! or A",essing lhe £f!el:IH,!Chemicol, on Reproducliw Fun"'io'"
fetal blood can be obtatned a nd used for prenata l diagnosis of hemoglobin
disord ers (Mac Kenzie and Macit an. 1980),
Felo scopy contro lled intrau terine sbn and muscle biop, ies are posllble and
promising for dlagn o>el of disordm which are nN detectable from amniotic
fibro blam . Fe,oscope can be also used for ' he contr ol of intr auterine
transfus.io n.
3.3 "' ....· In... s.. .
1.3./
~ I.lh""s
in Pr enata l o;.gnosis
Ullrosonograp/!y
Using real.t ,me ultra"'n ic ,"stru ment> rhe concep'us can be ,'i, u.lized during
5,h or 6th geSlauonal ,,<:ok>; and its growth. po'i'ion and localiza'ion of the
placenta can be monitored (Jou pilla and Piiroinen. 1975), T he iner. a.. in the
biparietal diameter is normally' used for general gro" 'lh evaluallon (Queehan (I
al .. 1976). £ "im auon$off etal bod y and h.a d wlumolare perfor med ,o d,agno"
intrauter ine growth retardation (Jordan and Clar k. 1980).
The fetal bea .. rate and the ~t of umbIlical arteri... can be also visualized
ultra sonically, The follo"'ing malformatlonl can be dia gnoled prena tally by
ultra sound procedure" anencephalI at ,he beginning of the second trimeste r:
mle lomeninlloceles. but diagno sis mal be difficult (Campbe lL 1977) : hydrocephalus and microcephalI in the 'h"d tnmester. inienceph. ly, sacrococ.
cygeal teralOmas . mullicyst'" or po lycl'tic b dneyl or hl dronephrosis and
omp haloceles "i'ualized as masses in a chara ctcri' ti< location (Bartlel et al ..
1977). In some case'. the ,hape of external getnta l,a allo"" the diagnos is of se•. In
the laSlt"me 't er, [he heart ,,,IHI an d ca,'i,ie, ca n be visualized an d the dlagno<is
of gross conge nita l heart anoma lies i. pos",b le (Patel and Goldberll. 1976).
3.3.2
RlUiiogr"!'h"
The u.. of dL,",,' radiograp hy for diagno' i' of skeletal defects i' Iimiled to the
trurd l" moster, During second trime"e t even llIos, .n oma li", such as achon dropla. ia arc undetectable (Golbus an d Hall. 1974). Prenatal radIo graphIC
diallflo'is (aft er JOIh gestat ional w..,k) of anencepha ly. hy'drocephal;. m;croc·
ephaly and of mOStof thellI o" skeletal anoma lies has been reponed , Contrast
radioirap hy with a water·,ol uble radio-cool ral! d;~1 hOIbeen used in the ' hlrd
tnm "' ter fot vi,ua liut ;on of ab$cnt fc'a l "wallowing in Case<of ga't roint""t inal
aU""ta
4 CO:->CLt:SIO:\'S
The elucida tion of lleneti<. biocheml, a l a nd ph}'>iological mcchan ilm. in'ol' "ed
io prenatal morphogcnes is . nd embryon ic funcuon il a nec",,$ary prerequisite for
MellwdJ for na lualing and Prroicling Human Ftrallk> 'elopmelll
309
atlemp, ini ,he prediclio n of adye,... etf""ts of chemica l agents On the exposed
mo ther and fetu •. To pmlic t 'he elf""t. of xenob io'ic subs,ances on prenatal
d,, 'elopmen t, ' he " ai e of pregnane; a, "hic h 'h e fet us was exposed and the
eXl'O' ure coneen,ra,io n need to be known. Predic' ion' based on animal
embryo,oxic ity and ,era,oienic i,y are, however, of limited "a lue.
For detection of inadequa,e fetal grow,h, chromO$Omal and me,abo lic
disease< and e"er nal ana' om ica l malformations. ,he folio" 109methods can be
used :<;1oIOiYof cell. exfol iated into ' he am niotic fluid, direc' biochemic.1 tests
of .mn ioloc fluid, kal;-ot; 'ping of amniotic ,·ell. grown in ,i'sue eulture' ,
biochemICal ana l;sis of amnl o, ic cells grown in ,issue cultures . fd oSCOp; .
analy. is of fda l hlood wi'hdr awn uooer fetoscopica l contlol, ult raoonography
and rad iograp hy of ,h. fetus
5 RE FER EN C ES
AI,·a,,', . H . a nd Cak\¢><o-lUrcla. R ( 1950), Conlrl« tilitj' of tlie human ute", . r«o rded
h) ne" method•. Su"l . Gy ""o l. Oh"" .. 9 1. I I) ,
A, .. " . 1\ S.. RauI.mo. L.. and p, l,onen . T , ( 1%0),
0/ ",m ~ hlood jlo ~'
and
"," abolism. A """. 1. Obm l . Gy" ecN .. 79. &(;_98
ll. rt ),,)' J. A .. Golbu,. M, S__FIlly R. A.. and Ha ll. B. 1).1 1977). Prenat a l diasn <>Si
' of
dy, p","" ktdney disease CIt". Ge",,' .. 11. 375-3 J%.
Broc• . D. J . H, 1 '9 7~ ) . Alpna-felOpr",ei n in the prenata l J i . ~nn>i, nf n",,,,1 tube J . fecl>
'n l ittlefiekl J. W .. J . Grouch). J... nd Ehhn ~ 1. J. 8. (Ed• .). Bi"h DejeclJ. P'o< . 5th
In« , n. tI,," al Conf .... nc• . Excerpt a ),led . Foond., Amsterdam a nd Oxford
Brock . D , .nd Sutchi fk R (' 972). Alph • •fotop ro" ,. In t be anten ~.. 1 diagno'" of
anencep ha l;- a nd spm. bifid> La. cel. 2. 197-1 9\1.
Bu'l . Ii . Hebb . C . and R. t!;o,·... C (l% n Cho lIne a,;et) la.. in tbe h"ll1an pla"n ta at
diFferent ,,~ ~ es of d<,.. lop ment. .\ "111
'" ,Lan duil I, 19\1. 1202
Campbe ll. S. ( 1977). Ear l) prenot a l draino ,", of neu", 1tu be defect, b;- ultra soun d , 0,",
Ob" " . (; , ,,<!C
oI.. 2(1. J5 1 -J ~9
Chop .. . I J.. and Cranda ll. B. F. ( 19: 1). H yrotd hormone >a nd th jTo trop in In a mnIotic
fluid . .\ e ~ Engl. J. Med ., 293. 740- 743
Clemen<>, J. A. Re)'<'S, F. L. W inter . J S, and Farman . C . ( J976) . Studies of human
se, ual d. " lop ment. "L Fe, . 1p" Ulta ' l , serum . nd amn iotICfluiJ concentra tIon of LHCO a nd FSH J . Gin. EmJ« riJlol. M " ab . 42, 9- 19
Du·ood . .\1 ) . anJ Sa",,"". B. 8 . ('977), Te""' terone and dihydro te""' te,one In
mate rna l .nd cord hlood and m amniollCnU'd .
1. Ob" .,. G.""erol.. 12'l. 37-42
De 1\1o"a. J . F. ( ' %3), Tb<: ni>tocbemical demonstr. tlon In ,tie num. n placen ta of
monoamine o,i&", .cti,· i'y by te,' azohum SIllts. A",., . J. Ob" ,,- Gp >erol.. 87. 27- 32,
Gan t. D. W .. . nd DJ.. r. D .c. ( 19J'). d-L)"..,.p: octd dietny ",m'ne (LSD -2l ) a
oonstr icto r of h"nlan umbi lical \ ,in . Lif' S<i.. 10. 2J ~ -2,j(),
Gol hu •.. M S.. "a n. Y W.. ~ nd N'i'och --eraill. M ( 1976). Feta l blood .. mphng tn
m,dtn~te' pr'll"" r.cles. A"" , J Obs'eI.6.1'''' ''''''' 124, 653-65 5,
Gol b" , . \ 1 S... nd Ha ll. B. D . ( 19' 41 Fa ilure to dial" O><achondrop 'a ' ia 10 utero
La.cer. I. ~29
Grumboch. M. M.. a nd Ducl"u me. J R ( 1%0) . Th' elf", ,, of a nJ ros . n, on feta' se. u. 1
Joy', lopm,n,. f'''il. S"" i.. 11. 157-180
Hog<rman , D . D , (1%9 ), ElIZ)molo~) of ,h' pt..tnUl . In KlopPC". A . ~nd Dic:<falu» . E,
(Ed ,.) FeI'" and Placenla, pp 413-469. Bloch ,.ll. O' ford
"",i""
Jf""""",,"'
A"",.
310
Mellwdsfor
A S~SJing
Ine Effects oj CMrnical. on Rep r'JdUC/i"e FrmClimu
Hor",y. J D. Fa rra r. J F._Gray. J , B., ond Dunlop. I. C ( 1% 4). Aroma", drng' and
congtnil~I
cataracu. 1.,mm.I
~12
Herbs,. A. L Ulf, ld... H.. and P""'anzer. D. C (197 1). Adenoca rcinoma of the ' -agma
Associallon of ma"rna l "ib<Jtro l th"'pl" with ' umor appear a""e In )'ounil v.omen
N, . ' eng!. J. M.d .. 28-1. 87&-S81,
Howard, J.. and Rudd. N L ( 1977), The notu.. 1 hi"o ry of a"' inopterin_induced
,,,,b ')'Opathy, In Ber¥"na . D"and Lo~l). R B (Ed., ), Bu'k Def«" Orig. Art. Ser..
Vol. XIII. No lC , pp. H-9 l\ M, ,,,h of D,,,,,,
J".>o k. J. E.. Stroufo, " , A.. Zv.·m¥"r, A. , Zido"' kj', J. (198<1)
. !'reo .. al de""",m a"on of
feu.I .. , ond ",,"'torone o",o io'''' <One."" a"on . (00 C=h) . C.Jk Gyo'k ol.. im.
I l)< 106
Jo'dan . H , V F ., ood Cia, • . W . B. (1980). Prenata l d<tertmnatlOn of f<ta l bam ond
v.'ei¥ht h) uhra",und . A .... r. J. Obs" '. Gy", c" 1.J6, S4-$9,
Jouppina, P, and PiL'o'nen. O . (197.\), Ultra",ni" <IiognOii. of f'ta l life 10 ..,1 Y pr<gnanC)'
Olmel. GJ"ecoi 46. 6 16--6;!(1
Junp""nno, ". C .. H .. 7onoL F " Hoor . J , ond Z,do "k~. J, ( 197.\). I" ' WO ,nl.= I' oo
of prost agtandin F,. ,nd oay1ocm 10 pla<ental ,·
1. J . reprQd. M~ .. 14 . l,, -14
MooK<tll... Z .. and ~lodo an . D, A, ( 1980), p"," f 1blood from lhe umb,I"a l cord
obt ai"e<! a t f<t""',,!,)', E,peri<ne. ~ i,h 1"$ , on u,;, .. ".. e• . Amer. JO b""
Gynecol.. 138. 1214--1218
MallCmi. R . ond GOUlt.. , R F. ( 1964). ElIect of certa in dnli' on p<rfu'«l hu"'an
plo.<:enta IV Delect ,on of >pe<ific receptor .n«. J. plwrm Sci, 53, 1476,
Mathu" V. S... n<!Wa lker, J. M (l96S ) O,ytocin, ,,, in p ta,rna and pl... nta ,n norma l
and pmlon ¥ed labo r em. meJ J., 3, 96-97 ,
Mal'ioh •. A. J" and Or<utt. R . E , ( 1960). P..."ureo ,n human umbilical ,-"",Ii in u'<ro,
Am" . j, Ob,u' (i1·", coJu lltl. lD _lJ6.
~l" kin , B. L. ( 1976). P<rl""<a!PllarmoeawgJ ond T,,,,,,,,,,ic • . An<!e m ~ Pr. ". :O;ev.
'
Yor k, san Francisco, a nd Londo n
i' l. L . L. " oi. (1980). Ammo tic ftuid concentr otion; of
Pang. S.. l<:'in a , L S" Ce<\.T<i,
ro,y l''''
...' and e- >tOroid. in f<tu"" v.nhmngen itolad ... ", 1hypelplo.ia due to 21_hY'd
d<oo<IICyand m .n.lICepho l'" fetu ... . J. d in. bIdocrilwl . M " ab" § l. 223-229
Patel. J.. ond Goldb<r~. B. B. (1976). Prrnta l genelic diagn<»i•• nd ultr o>ougrophy Cl<o,
Ob,"'. Gp vc oJ.. 19. S93 907.
Quee han, J T.. Kuba, yc h, S F" Cook , M N eta l, (1976) . Di agn"' l'" " I"o so"nd for
detection of i" ,raulertn< growth "'t. , dotion ,1m" . j . Ob" .. . GJ" ' roJ.. 124. Il6j-S 7)
Rhin., S. (1976). P,"n".l gen.l'" d,agnoslS . "d metabo l", d,so.-.:l. .. . Oin . Ob""
Gyn" ol" 19, 81~
R,ddick. D . H.. a n<! .\ lo. kr , l. A. (198 1). Ttl< tran .port af prolac'in b,' human f... 1
membran .. . j . Oin , &00",,001 , Melab .. 52. Z2O-224
Ruosel. L B.. and Ruosel. W L. (19$4). An 'n,l j"; ' of l h« ha ng,ng .. d,a loon' eopon", of
lh< d,, ·. lopini tn<>u",,mbryo. J . cell <Q"'" Ph)·soo/. Suppl. I. 39. 10)- 147
sa"'u. S.. Chanil . H C . POlfee<>,R. P . a nd Jon es. 0 . W. (I'IW ). N<ural oril;in of ", II. in
. mnio' ic ftuid. AM£R . J . Ob,,,,- G,'", wI .. 136. 67-72
S","' . L.. "nd R. po ta. J ( 1969). Cotli<nno l Defect>. Holt , Rtn, hart \\ \Olton. .'- 0'" Yor k
' or< n,. and
Schilf. D .. Arand •. J. \ , ,nd Stem . L (l9 JQ). :O;.O"al, 1 ' hro mbt::lCY
cong<n" a l "'a lforma "o" ' a osoc"' le<lV.,lh the ad m,n'st," " on of tolbutamid, to the
.. 17. 457· .S8
mOlher. J. P<JioJl
Schwalb<, E. ( 1906) M w b,iJ,,"g'/eh., (T"ol("o~i,) . F,"'l>er. J.n,
5ee<I•. 11.. E.. Leun!!. L. S.. S')-~ . S, J. ¥I ai , ( 1980,. Compa"son of human a n<! . heep
. /l-h)d,o' j!>utjn te and glycerol A""" J. Ob"".
chnon lan e, p<rm<abili,y of aI""oo<
Gy", "" ., 1.l3, 604--614
>01l\Il
''''
A"",.
Shl". E. B. (19721. F.... I dunOI' du< 10 nal<m ol .m inOpt<rin ;ng«",,"
J DiJ,
Oild .. 1!oI. 9J.-96
Shaul. \\ L.,.n<! Hi ll. I, G . (19711. MuJ" ple cocrnlala""rnah .. a"o<""ed ,," h oral
(;yntroi.
Il7 , 1~1-19I
.nticOOI"lIn" . A",..... I,
Simpson. J. L.• • n<! Ma ' lln. A. C. (1916). P...... ,.I dloiT\QSI, of C~l_ 'i< diSOrdm,
Clin O~Sltt. (;)'1"«)/,, l ~. S41-8 S3
abortion, ",h",h 0 rol" ""Ol .... Ion'S!. 4-om ,oopThi.""h. J. B. (1952). Tb<npe"'"
' .. c}'IJlua""" "" Ol od""ni"e=l
by Ih< oro! reut •. A"",. J. Ob"., . GJ""«)/ .. 63.
1298 1304
Tool!'. R.. on<! R", '>d, R. (1968). 10 M'~'" L. on<! P.cL H M. ( EM ), l>nitfNJu.d
DiMtlYs, E..c.rp<a Med F"'md., Am".rdaIn,
Wo' rel, D . W.. and To~'Ior, fl., (1968), OulCOm. fo, th< fotu' of mOlh<" ,« .j ", nl
pr«lnlsolono dun nl P....... ""~· Laou'. 1. J 17-1 19
\Veinl o ld. A B.. In<! Scu'bem. A. L (1968), Di.olllln< cxldo .. 0' on 'nd<x of 'h<
ftlOptKenll1 .ni, 06".,. Gp,u<JI.. 32. 593-600
Wilscn. ]. G, ( 1912), E"",,,"men," 1
On d<,<IOp"",n, ,."uol"l}" . In A, .. Io. 1'. S
(Ed.), /'o,~op/t,sO:JJcrYQJ
Vol. II, p!', 210- J2().Acad. """ P..... N. . ..Yor k
Ob,,,,.
df"'''
wsro,"".