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: S perm Injection in Pig A ctiv ation of P orcine Oocy te s F ollow ing Intracy toplas mic Injection of V arious S perm Com ponent s and f oreig n s pe cie s sperm atozoa

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(1)

불 임 학 회

요 약 제 목 : S perm Injection in Pig

A ctiv ation of P orcine Oocy te s F ollow ing Intracy toplas mic Injection of V arious S perm Com ponent s and f oreig n s pe cie s sperm atozoa

S .H . Ju n , J .S . S hin , J .T . D o , J.K . K w on

*

, N .H . K im , H .T . L e e , K .S . Ch un g

A nimal R esource R esearch Center, Kon Kuk University,

*

L ab of E lectrom icr os cop y , m ed ical s chool, H anyang un iv ers ity

여 러 가 지 정 자 구 성 성 분 및 이 종 정 자 주 입 에 의 한 돼 지 난 자 의 활 성

전 수 현 ・ 신 지 수 ・ 도 정 태 ・ 권 중 균

*

・ 김 남 형 ・ 이 훈 택 ・ 정 길 생

건국대학교 동물자원연구센터, *한양대학교 의과 대학 전자현미경실

본 연구에서는 돼지 난자내에 돼지정자, 여러 가지 처리된 정자두부(1% T rit on , 0.1%

T r y p sin , 100m M N aOH ) 및 이종정자 (소, 쥐, 사람)를 미세 주입한 후 난 활성과 웅성 전핵 형성, 전핵의 이동 및 배발달을 관찰하였다. 전자현미경으로 관찰한 결과 T rit on X - 100을

처리하였을 때 첨체가 제거되었으나 핵 주변 물질은 제거되지 않았고 T ryp sin 또는 N aOH

를 처리 할 경우 핵주변 물질(perinuclear m at erial)이 제거됨을 볼 수 있었다. 돼지난자는

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정자, 정자두부 및 T riton X - 100을 처리한 정자두부의 주입을 통해 난 활성이 유도되었으며

쥐, 소, 사람의 정자를 주입하였을 때 난 활성이 유도되고 정상적인 전핵형성이 이루어졌다.

그러나 정자꼬리나 T ryp sin 또는 NaOH에 의해 정자 핵주변 물질(perinu clear m aterial)이

제거된 정자두부를 주입하였을 때는 난 활성은 야기되지 않았다. 유사분열 및 2- 세포기까지

정상적인 수정은 동종의 정자 및 정자두부를 주입한 난자에서 관찰할 수 있었으나 이종정자

를 주입한 난자에서는 관찰되지 않았다. 또한 상실배 및 배반포까지 정상적인 수정은 동종

의 정자 및 정자두부를 주입한 난자에서 관찰할 수 있었다. 이러한 결과는 돼지에서 정자

및 정자두부의 미세주입에 의해 수정이 이루어지는 것을 시사하며 수정시 정자유래의 난활

성인자는 정자 핵주변 물질(perinu clear m at erial)에 존재하며 종특이적이지 않다는 것을 보

여주는 것이다.

(K ey w or d s : P or cin e eg g s , ICS I, F er t ilizat ion , A ct iv at ion , P er in u clear m at er ial )

. Intro du ction

Dur in g fer tilizat ion t h e sp er m cell a ctiv at es oocy t es b y r elea sin g an oocy t e

a ctiv at in g fact or (s ) (OA F ) in t o oocy t e s . P ar r in gt on (1996) r eport ed th at OA F is a 33

k Da pr ot ein r esidin g in th e equ at or ial s egm en t r egion of th e acr osom e. B ecau se

int r acy t opla sm ic sper m inj ect ion of for eig n species , su ch a s h am st er , r abbit , pig , hum an

or sea ur ch in in t o m ou se oocy t e s act iv at es oocy t es , OA F is n ot str ict species specific

for t h e m ou s e oocy t e (W ak ay am a et al., 1997 ; Kim ur a et al. 1998 ). In t h e m ou s e OA F

appear s (or b ecom e act iv e ) in sper m iog en esis an d locat ed in t h e perinu clear m at er ial

(3)

(Kim u r a et al., 1998 ). H ow ev er , infor m at ion is lar g ely lackin g on t h e n at ur e of act iv at ion

fact or s for any sp ecie s ot h er t h an th e m ou s e.

T o g et in sigh t int o t h e n at ur e of sper m b or n oocy t e fact or s , w e det er m in ed th e

in ciden ce of act iv ation , m ale pr on u clear for m at ion an d pr on u clear app osit ion follow in g

inj ect ion of v ariou s p or cin e sper m com p on ent s an d for eig n species sper m at ozoa in t o

p or cin e oocy t es . In t h e pr es ent st u dy w e als o ex am in ed dev elopm en t al ability in v itro

follow in g inj ect ion of a sp er m at ozoon an d an isolat ed sp er m h ead .

. M A T E R IA L S A N D M E T H OD S

1 . I n V it r o M aturation

P r epu b er t al p or cin e ov ar ies w er e collect ed fr om a local slau g ht er h ou se an d

t r an spor t ed t o t h e lab or at or y at 25°C in Du lb ecco ' s ph osph at e bu ffer ed salin e

supplem ent ed w it h 5.54 m M D - glu cose , 0.33 m M sodium py r uv at e, 75 m g/ m l pot a s sium

p enicillin G an d 50 m g/ m l str ept om y cin su lph at e (m DP BS ). Cu m u lu s - Oocy t e com plex es

(COC ) w er e a spir at ed w it h an 18 - g au g e n eedle in t o a disp os able 10- m l sy r in g e fr om

follicles . F ift y por cin e COC w er e m atu r ed in 500 μl of B S A - fr ee N CS U 23 (P et t er s

an d W ells , 1993 ) m ediu m su pplem ent ed w it h 10% p or cin e follicu lar flu id , 0.6 m M

cy st ein e, 10 IU/ m l P M S G (S igm a , S t . Louis , M O, U S A ) an d 10 IU/ m l h CG (S igm a )

u n der par affin oil at 39°C for 40 t o 44 h .

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2 . P reparation of s p erm at oz o a an d i s olat e d s perm h e a ds

P or cin e sp er m - r ich fr action (15 m l) w a s collect ed fr om a b oar by g lov ed h an d

m et h od , an d , aft er addin g an tibiot ic - an t im y cotic solu tion (S igm a ), t h e sem en sam ple w a s

k ept at 20°C for 16 h . S em en w a s w a sh ed 3 tim es by cent r ifu g at ion w it h 0.9% (w/ v )

N aCl su pplem ent ed w it h 10 m g/ m l BS A (fr act ion V ; S igm a ). S per m at ozoa w er e

su spen ded in 1.5 m l of T L - HE P E S (P r at h er et al., 1995 ) for 30 m in t o in du ce

capacit ation . T h e isolat ed sper m h ead s w er e obt ain ed b y t h e m et h od r epor t ed b y t h e

Ku r et ak e et al (1996 ). T h e sp er m su sp en sion w a s son icat ed in 9 m l of cold n u cleu s

isolat ion m ediu m (NIM , Ku r et ak e et al., 1996 ) in t h e pr esen ce of 0.05% t rit on X - 100.

T h e sonicat ion w a s con du ct ed in w at er b at h for 30 s ec u sin g 100 % ou tput of an u lt r a

s on ic s on icat or (M odel, Br an son 8210). T h e sonicat ed sper m su spen sion w a s dilu t ed an d

cent r ifu g ed for 5 m in at 1,000 x g t o th e sper m h eads . T h e sperm h ead s w er e on ce

m or e w a sh ed in 10 m l of NIM b y cen t rifu g ation . F or an ot h er ser ies of ex p er im en t s

isolat ed sper m h eads w er e tr eat ed w ith 0.1% tr y p sin or 100 m M N aOH s olut ion for 3 h

in t ris buffer ed salin e. S om e sp er m h ea ds w ith or w it h out tr eat m en t s w er e fix ed in 2 %

g lu t ar aldehy de in Du lb ecco ' s ph osph at e - buffer ed s alin e. T h e sp ecim en s w er e t h en

p ostfix ed in 2% Os O4 for 1 h , dehy dr at ed in a gr aded eth an ol ser ies , an d em b edded in

epox y r esin . Ultr at hin section s w er e cut w it h a diam on d kn ife an d post - st ain ed fir st

w it h 1% u r any l acet at e in 30% et h an ol an d w ith R ey n old s lead cit r at e. A t r an sm is sion

elect r on m icr oscope (Hit achi 600, H it ach i Lt d, K a shiw a , J ap an ) w a s u sed t o det er m in e

t h e pr esen ce an d ab s en ce of per in u clear m at er ial.

Hu m an ej a culat ed sem en sam ples w er e ob t ain ed by m a st ur b at ion . S em en w er e

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m ix ed w it h an equ al v olum e of H E P E S - bu ffer ed h um an t ub al fluid m ediu m

(H T F - P ep es , Ir v in e S cien t ific, S ant a A n a , CA ) an d cent r ifu g e for 5 t o 10 m in at 1800 g .

T h e pellet w a s su sp en ded in 1.5 m l of H E P E S - b uffer ed H T F - P ep es t o in du ce

capacit ation . M ou s e sp er m at ozoa w er e collect ed fr om a m at ur e m ale m ou se (ICR , 8 t o

13 w eek old ) cau da epididy m is e. S p er m at ozoa w er e w a sh ed in T L - H E P E S an d th en

su spen ded in 1.5 m l of T L HE P E S . Bov in e sp er m at ozoa w er e pr epar ed fr om

fr ozen - th aw ed s em en . S per m at ozoa w er e w a sh ed t w ice w it h T L - H E P E S an d t h en

su spen ded in 1.5 m l of T L - H E P E S . T h e sper m w a s r esu spen ded t o 1 m l w ith

h epar in - cont ainin g (10 u g/ m l) T L - HE P E S in a effen dor f t ub e an d k ept at 39 C for 30

t o 60 m in t o in du ce cap acit at ion .

3 . Oo cy t e A ctiv ation

T h e pr ocedur es for elect r ical st im ulat ion of por cin e oocy t es w er e a s des cr ib ed by

Kim et al (1996a ). E lect r ical st im ulat ion t o in du ce act iv ation w a s deliv er ed w ith a BT X

E lect r o Cell M an ipulat or (Biot ech n ologies an d E x perim ent al Resear ch , In c., S an Dieg o,

CA ) t o a ch am b er w it h t w o par allel plat in um w ir e elect r odes (200 m m o.d .) spa ced 1

m m ap ar t ov er laid . A t 30 t o 60 m in b efor e sper m cell inj ect ion , cu m ulu s cell denu ded

oocy t es w er e st im ulat ed b y a 10 sec pulse at 0.48 KV/ cm A C follow ed by a 30 m s

pulse at 1.26 kV/ cm D C at r oom t em per atu r e (25°C ). T h e oocy t es w er e th en tr an sfer r ed

t o 500 m l of N CS U 23 m edium an d cu lt ur ed at 39°C in an at m osph er e of 5% CO

2

in air

u nt il sp er m cell inj ect ion .

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4 . S perm at o z oon inje ction int o O oc y te s

S per m at ozoa w er e cent r ifu g ed (400g , 5 m in ) an d r esu spen ded in T L HE P E S : 10%

p oly v in y lpy r r olidon e solu tion (1:1). A m icr odr op (5 m l) of t his su spen sion w a s placed a

slide , an d t h e slide w a s placed in L eit z Differ en t ial In t er fer en ce Cont r a st inv er t ed

m icr os cop e equ ipped w ith L eit z m icr om anipulat or s . T h e oocy t es w er e denu ded of

cum ulu s cells by r epeat ed pipet t in g . Oocy t es w ith v isible polar b ody an d of ex cellen t

m or ph ology w er e u sed for t his ex per im ent . Oocy t e s w er e cen t rifu g ed for 10 m in in an

E ppen dor f cent r ifu g e at 12,000 g in 50 m l T L - HE P E S m edium in 1.2 m l E ppen dor f

cent r ifu g e t ub e. T h e inj ection of sper m at ozoon or is olat ed sp er m h ead in t o th e oocy t e

cy t opla sm w a s per for m ed u sin g t h e m et h od of L ee et al (1998). Br iefly , t h e inj ection

n eedle u s ed w a s of 6 - 7 m inn er an d 8 - 9 m ou t er diam et er . T h e p olar b ody w a s at 6 or

12 o ' clock an d t h e p oint of inj ect ion at 3 o ' clock . A n oocy t e w a s p en etr at ed by t h e

inj ect in g m icr opipett e, a sm all am oun t of cy t opla sm w a s dr aw n in t o t h e m icr opip ett e,

an d t h en th e cy t opla sm t og eth er w it h t h e sperm at id an d a sm all am ou nt of m edium w a s

ex p elled int o t h e oocy t e. Im m ediat ely aft er oopla sm ic inj ect ion , t h e inj ect in g m icr opipett e

w a s w it h dr aw n qu ickly , an d t h e oocy t e s w er e r elea sed fr om t h e h oldin g pip et t e t o

r edu ce th e int r acy t opla sm ic pr es sur e ex er t ed t o t h e oocy t e. A ft er inj ect ion , all of th e

oocy t es w er e t r an sferr ed t o N CS U 23 m ediu m an d cultu r ed for at 39°C u n der 5% CO2 in

air . T h e oocy t e s w er e fix ed at 10 t o 15 h an d 20 t o 24 h follow in g sper m cell inj ect ion .

A b ou t 10 oocy t es w er e fix ed , st ain ed w ith 1% (w/ v ) or cein an d ex am in ed n u clear

m or ph ology at 200 X an d 320 X m ag nificat ion w it h ph a se cont r a st m icr os copy . T h e

ot h er s w er e cu lt ur ed for N CS U 23 m edium at 39°C un der 5% CO2 in air .

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5 . Ch rom o s om al an aly s is

A t 22 h follow in g inj ect ion , t h e oocy t es w er e cu lt ur ed in cu lt ur e m ediu m in th e

pr esen ce of 5 u M colcem id. T h e oocy t es w er e t h en cent r ifu g ed t o r em ov e lipid s in t h e

cy t opla sm , an d placed in a h y pot onic solu tion of sodium cit r at e (1% ) for 5 m in an d

fix ed in div idu ally on m icr oscope slides b y t h e air - dr y in g m et h od (T ar k ow ski, 1966 ).

T h e oocy t e s w er e st ain ed w ith 10% Giem sa at pH 6.8. T h e chr om osom e con stit u en t of

each spr ead w a s det er m in ed at 1000 m a gn ification w it h a Zeis s m icr oscope.

6 . S tati s tic al A n aly s e s

T h e dat a w er e p ooled fr om at lea st four r eplication s . Differ en ces in th e per cent ag e s

of oocy t es dev elopin g t o a p ar ticu lar st ag e w er e det er m in ed by Ch i- squ ar e pr ocedu r es .

. R E S U LT

F e r t iliz a t ion of p or c in e oocy t es f ollow ing inj e c t ion of sp e r m a t oz oa or is ola t e d sp e r m hea d

T h e oocy t es w ith t w o lar g e pr onu clei an d t w o polar b odie s (2 P N + 2 P b ) w er e

cla s sified a s n orm al fert ilization at 10 t o 15 h follow in g ICS I or int r acy t opla sm ic sp er m

h ead inj ect ion (T able 1). T h e in ciden ces (52 t o 56 % ) of n or m al fer tilization w er e n ot

differ en t b et w een follow in g sper m at ozoon an d sp er m h ead inj ection . T able 2 sum m ar ize

(8)

chr om at in config ur at ion in por cin e oocy t es at 20 t o 24 h aft er sperm at ozoon or isolat ed

sper m h ead inj ect ion . T h e in ciden ce of pr on u clear apposit ion , m it osis an d t w o cell

div ision w a s con sider ed a s n or m al fer t ilized . F ollow in g ICS I an d h ead inj ect ion , 49% an d

44% w er e n or m ally fer tilized, r esp ect iv ely .

T able 1 . Chrom atin c onfig u ration s in pig o o cy t e s at 12 t o 15 h f ollo w in g in tra cy t opla s m ic s perm ato z oa or i s olate d s p erm h e ad

P ar am et er a s se s sed T y pe of cells inj ect ed

S h am S per m at ozoon S per m H ead N o. of oocy t es

a

su cces sfu lly inj ect ed (r eplication ) 51 ( 5) 60 ( 5 ) 62 ( 5 )

w it h t w o P N an d t w o P B (% ) 0 ( 0) 31 (52) 35 (56 )

w it h on e P N , sper m h ead an d t w o P B (% ) 0 ( 0) 9 (15 ) 5 ( 8 ) w it h t w o P N , sper m h ead an d on e P B (% ) 0 ( 0) 2 ( 3 ) 4 ( 6 )

w it h th r ee P N + on e P B (% ) 2 ( 4) 5 ( 8 ) 6 (10)

w it h t w o P N + on e P B (% ) 9 (18) 1 ( 2) 0 ( 0)

w it h on e P N + t w o P B (% ) 36 (71) 0 ( 0) 0 ( 0)

w it h oth er s

b

4 ( 8) 12 (20) 12 (19 )

a

A bb r ev iat ion s : P N , pr on u cleu s ; P B ; p olar b ody .

b

Ot h er s in clu de t h e oocy t es w it h out or un iden tified m u lt iple n u clei.

T able 2 . Chrom atin c onfig u ration s in pig o o cy t e s at 20 t o 24 h f ollo w in g

in tra cy t opla s m ic s perm ato z oa or i s olate d s p erm h e a

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P ar am et er a s se s sed T y p e of cells inj ect ed

S h am S per m at ozoon S per m H ead N o. of oocy t es

a

su cces sfu lly inj ect ed (r eplication ) 49 ( 5 ) 6 1 ( 5 ) 62 ( 5 )

closely app osed 2 P N 0 ( 0 ) 20 ( 33 ) 18 ( 29 )

M it osis 1 ( 2 ) 2 ( 3 ) 3 ( 5 )

T w o - cell 2 ( 4 ) 8 ( 13 ) 6 ( 10 )

w it h t w o P N an d t w o P B (% ) 0 ( 0 ) 7 ( 11) 14 ( 23 )

w it h on e P N , sper m h ead an d t w o P B (% ) 0 ( 0 ) 9 ( 15 ) 5 ( 8 ) w it h t w o P N , sper m h ead an d on e P B (% ) 0 ( 0 ) 2 ( 3 ) 4 ( 6 )

w it h t w o P N + on e P B (% ) 10 ( 20 ) 0 ( 0 ) 0 ( 0 )

w it h on e P N + t w o P B (% ) 27 ( 55 ) 0 ( 0 ) 0 ( 0 )

w it h oth er s

b

9 ( 18 ) 13 ( 21) 12 ( 19 )

a

A bb r ev iat ion s : P N , pr on u cleu s ; P B ; p olar b ody .

b

Ot h er s in clu de t h e oocy t es w it h out or un iden tified m u lt iple n u clei.

O ocy t e a c t iva t ion and p r on ucl ea r f orm a t ion f ollow ing inj e c t ion of va r io us sp e r m c omp one nts

T ab le 3 su m m ar izes t h e in ciden ce of act iv at ion an d m ale pr on u clear for m at ion

b et w een 10 t o 12 h follow in g inj ection of v ar iou s sp er m com pon ent s . W h en a

sper m at ozoon or T r it on X - 100 t r eat ed por cin e sper m h ead s w er e inj ect ed int o por cin e

oocy t es , th e oocy t es w er e activ at ed , w h er ea s t ail did n ot in du ce activ at ion . Inj ect ion of

eit h er t r y p sin t r eat ed sper m h ead or N aOH t r eat ed sper m at ozoa failed t o in du ce

a ctiv at ion . M ale pr on u cleu s w a s for m ed in th e a ctiv at ed oocy t es follow in g inj ection of

T r it on X - 100 t r eat ed sp er m h ead . N eith er t ry p sin n or N aOH t r eat ed sp er m h ead w a s

decon den sed in por cin e oocy t es w h en t h ey w er e inj ect ed . T r an sm is sion elect r on

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m icr os copy sh ow ed sag it t al section s of is olat ed sp er m h eads aft er son ication in t h e

pr esen ce of tr it on X - 100 or t r y p sin (F igu r e 1). W hile T r it on X 100 t r eat m ent left

p er in u clear m at er ial ar ou n d t h e n u cleu s , tr y p sin or N aOH r em ov ed per inu clear m at er ial

ex t en siv ely .

T able 3 A ctiv ation an d m ale pron u cle ar f orm ation in porcin e oo cy t e s at 10 to 15 h f ollo w in g v ariou s s perm c om pon ent s

S per m h ea ds t r eat ed

N o. (% ) of oocy t es su cces sfully

inj ect ed (r ) act iv at ed M P N

n on e 42 (5 ) 7 (17 ) -

sp er m at ozoa 25 (4 ) 19 (76 ) 15 (60)

sp er m h ead

1% t r it on 46 (5 ) 41 (89 ) 29 (63 )

0.1% t r y p sin 44 (5 ) 10 (23 ) 6 (14 )

100 m M N aOH 35 (4 ) 3 (9) 0 (0)

sp er m t ail 19 (3 ) 2 (11) -

M P N : m ale pr on u cleu s

F ig 1. S ag it t al section s of por cin e sper m h ead follow in g v ariou s t r eatm en t s . A ) In t a ct

sper m at ozoa , B ) S onicat d sperm h ead in th e pr es en ce of tr it on X , C ) T h e sper m h ead

cultu r ed in 100 m M N a OH .

(11)

O ocy t es a c t iva t ion and m a le p r onuclea r f orm a t ion f ollow ing inj e c t ion of f or e ig n sp e c ies sp e rm a t oz oa

M ost oocy t es w er e activ at ed at 10 t o 12 h follow in g inj ect ion of sperm cell

r eg ar dles s of elect r ical st im u lat ion (T able 4 ). A lt h ou g h som e oocy t es (23% ) w er e

a ctiv at ed in t h e oocy t es follow in g sh am inj ection , t h e r at es is v er y low . T h e in ciden ce

of a ctiv at ion an d pr on u clear for m ation w a s n ot differ en t in oocy t es follow in g inj ection of

p or cin e, b ov in e, m ou s e or h um an sp er m at ozoa (T ab le 4 ) in t h e ab sen ce of electr ical

stim ulat ion . A ddition al electr ical st im ulat ion did n ot in cr ea se t h e in ciden ce of m ale

pr on u clear for m at ion (P > 0.1). A t 36 h follow in g inj ection , m aj or ity oocy t es , w h ich

w er e inj ect ed por cin e sper m at ozoa , w er e cleav ed t o t h e 2- cell st ag e (T able 5 ). H ow ev er ,

n on e of oocy t es w er e n or m ally div ided t o t h e t w o cell st ag e follow in g for eig n species

sper m inj ection . A lth ou gh som e oocy t es w er e div ided t o t h e t w o- cell st a g e follow in g

sh am , m ou s e, b ov in e or h um an sper m cell inj ection , it app ear s t o b e du e t o

p ar th en og en et ic a ctiv at ion .

T able 4 . A c tiv ation an d m ale pronu cle ar form ation in porcin e o oc y te s at 10 t o 15

h f ollo w in g m ou s e , b ov in e , hu m an an d porcin e s perm inje ction

(12)

S ou r ce of sp er m at ozoa

elect r ical st im ulat ion

N o. (% ) of oocy t es su cces sfu lly

inj ect ed (r ) activ at ed M P N n on e

(sh am inj ect ion )

+ 28 (4 ) 26 (93) 0 ( 0)

- 26 (4 ) 6 (23) 0 ( 0)

pig + 55 (6 ) 53 (96) 34 (62)

- 50 (6 ) 42 (84) 29 (58)

cow + 52 (6 ) 50 (96) 31 (60)

- 52 (6 ) 43 (83) 23 (44)

hu m an + 54 (6 ) 48 (89) 25 (46)

- 59 (6 ) 39 (66) 31 (53)

m ou se + 50 (6 ) 49 (98) 36 (72)

- 51 (6 ) 37 (73) 29 (57)

T able 5 . cle av a g e an d nu cle ar s tatu s of porcin e o oc y te s at 36h f ollo w in g in tra cy t opla s m ic inje c tion of p orc in e , b ov in e , m ou s e or h um an s p erm at oz o a .

S our ce of sperm at ozoa

N o. (% ) of oocy t es su cces sfully

inj ect ed (r ) on e cell n or m al t w o cell

a

abn or m al t w o cell

b

sh am inj ection 15 (2) 11 (73 ) 1 ( 7 ) 4 (27 )

pig 26 (3) 5 (19 ) 17 (65 ) 4 (15 )

cow 27 (3) 17 (63 ) 0 ( 0) 10 (37 )

hu m an 25 (3) 16 (64 ) 0 ( 0) 9 (36 )

m ou se 29 (3) 19 (66 ) 0 ( 0) 10 (34 )

a

E m br y os w it h t w o int er ph a se nu clei

b

T w o t o fou r cell st a g e eg g s w it h a bla st om er e w hich h av e n o or m ultiple nu clei.

I n V itr o d e v e lop m en t of p or c in e o ocy t es f ollow ing inj e c t ion of a sp e rm a t oz oon or

is ola t e d sp e r m hea d

(13)

Chr om osom e an aly sis r ev ealed t h at m ost oocy t es am on g ident ified t h em (73% in

ICS I ; 70% in h ead inj ect ion ) w er e diploid follow in g ICS I an d isolat ed sperm h ead

inj ect ion . T h er e is n o diploid in oocy t es at 22 h aft er sh am inj ect ion (T able 6 ). T h e

m ost oocy t e s cleav ed at 24 h an d div ided t o 4 - cell at 48 h follow in g ICS I or isolat ed

sper m h ead inj ect ion (T ab le 7 ). H ow ev er , t h e sh am oocy t es cleav ed t o t h e 2- cell aft er

24 h . A t 7 day s t h e in ciden ces of b la st ocoel for m ation follow in g ICS I (38% ) an d is olat ed

sper m h ea d inj ection (22% ) w er e h ig h er t h at follow in g sh am inj ect ion cont r ol (3% , T able

8 ). S om e oocy t es follow in g sh am inj ect ion w er e dev elop ed t o b la st ocy st s at 9 day s .

T able 6 . Chrom o s om al an aly s i s of porcin e o oc y te s at 22 h f ollow in g s perm at o z oon or i s olat e d s pe rm h e ad inje c tion

T y pe of cell inj ect ed N o. (% ) of eg g s

t est ed ident ified h aploid diploid > t et r aploid

n on e 22 9 9 (100) 0 ( 0) 0 ( 0)

sperm at ozoon 26 15 2 ( 13 )

*

11 (73 )

*

2 (13 )

*

sperm h ead 25 10 2 ( 20)

*

7 (70)

*

1 (10)

*

*

P 〈 0.05.

T able 7 . Cle av ag e of porcin e o o cy t e s at 24 an d 48 h after s p erm at oz o a or

i s olat e d s perm h e a d inje ction

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T im es (h ) aft er inj ect ion

T y pe of cell inj ect ed

T ot al n o. of oocy t es inj ect ed

N o. (% ) of eg g s cleav ed t o

1- cell 2- cell 4 - cell fr ag m ent at ion

24

n on e 65 50 (77 ) 7 (11) 1 (2) 7 (11)

sper m at ozoa 65 13 (20) 45 (69 )

*

6 (9 ) 1 (2)

sper m h ead 65 16 (25 ) 38 (58 )

*

8 (12) 5 (8 )

48

n on e 65 15 (23 ) 32 (49 ) 6 (18 ) 12 (9 )

sper m at ozoa 65 8 (12) 10 (15 ) 38 (58 )

*

9 (14 )

sper m h ead 65 11 (17 ) 16 (25 ) 41 (63 )

*

7 (11)

*

P 〈 0.05.

T able 8 . In v itro dev elopm ent of pig zy g ot e s cu lture d for 7 an d 9 day s f ollo w in g s perm at o z oon or s p erm h e ad inje ction

T y p e of cell inj ect ed

N o. of em br y os ex am in ed (r )

N o. (% ) of oocy t es dev eloped t o bla st ocy st s at 7 day s 9 day s of cultu r e

n on e 65 (5) 2 ( 3 ) 8 (12)

sperm at ozoon 65 (5) 25 (38 )

*

29 (45)

*

is olat ed sp er m h ead 65 (5) 14 (22)

*

20 (31)

*

*

P 〈 0.05.

. D IS CU S S ION

Int r acy t opla sm ic sp er m inj ect ion (ICS I ) h a s b ecom e a r out in e clin ic pr ocedur e for t h e

t r eat m ent of m ale fact or in fer tility . Becau se inj ect ion of a sin gle sp er m at ozoon int o an

oocy t e b y pa s s es cont act an d fu sion b et w een t h e pla sm a m em br an e of b ot h g am et es ,

(15)

con cer n s h av e b een r aised h ow t h e oocy t es can b e act iv at ed follow in g ICS I. It h a s b een

k n ow n t h at in t h e hu m an dir ect inj ect ion of sper m at ozoa in du ce os cillat ory pat t ern of

Ca +2 r ise b y in t r odu ct ion of sper m b or n oocy t e act iv atin g fact or s (OA F , pr ob ably

oscillin , T esar ik et al., 1994 ). In t h e m ou se , t h e OA F appear ed t o b e a 33 kDa pr ot ein

r esidin g in t h e equ at or ial s egm en t r egion of th e acr osom e (P ar r in gt on et al., 1996 ). It

w a s als o kn ow n t h at in t h e m ou se OA F appear s (or b ecom e act iv e ) in sper m iog en esis

an d locat ed in t h e p er in u clear m at er ial (Kim u r a et al., 1998 ). Ou r ex p er im en t sh ow ed

t h at T r it on X - 100 t r eat ed p or cin e sper m h ead h a s ability of act iv atin g oocy t es .

H ow ev er , n eith er t r y p sin t r eat ed n or N aOH tr eat ed sper m aozoa did n ot act iv at e oocy t es .

T r an sm is sion elect r on m icr oscopy r ev ealed t h at p er in u clear m at er ial is b oun d tigh tly t o

t h e sper m pla sm a m em br an e, an d tr eat m en t of tr y p sin or N aOH r em ov ed per in u clear

m at er ial. T h er efor e, lik e in t h e m ou s e (Kim ur a et al., 1998 ), in t h e pig som e su b st an ce

in per in u clear m at er ial, w h ich is fir m ly at t ach ed sper m pla sm a m em b r an e, m ay a ctiv at e

p or cin e oocy t es dur in g fer t ilizat ion or follow in g ICS I. Our st u dy also sh ow ed t h at

int r acy t opla sm ic sper m inj ection of for eign sp ecies su ch a s b ov in e, m ou s e or h um an

a ctiv at ed por cin e oocy t es . P r ev iou s r esu lt s sh ow ed th at t h e m ou s e oocy t e s ar e r eadily

a ctiv at ed b y inj ection of h am st er , h um an , r abbit , pig or sea u r chin sp er m at ozoa

(Ry b ou chkin et al., 1995; W ak ay am e et al., 1997, Kim ur a et al., 1998 ). Collectiv ely , t h e

sub st an ce of oocy t e act iv at ion seem s n ot t o b e species sp ecific for t h e por cin e oocy t e,

lik e for t h e m ou s e oocy t e .

Dur in g tr an sit of sper m at ozoa t hr ou gh epididy m is , sp er m n u clei ar e v er y st able by

an ex t en siv e of cr os s - linkin g b y disufat e b on d of pr ot am in es , t h e sp er m specific b a sic

(16)

pr ot ein s , (Bedfor d & Calv in , 1974 ). F ollow in g sp er m pen et r ation int o oocy t e cy t opla sm ,

pr ot am in s ar e r em ov ed an d r epla ced by hist on es , an d t h e sper m nu cleu s w a s r em odeled

int o pr on u cleu s w it h a s sem bly of t h e n u clear en v elope . Redu ction of t h e su lfat e b on d by

g lu t ath ion e (S u t op ski et al., 1996 ) an d nu cleopla sm in fr om t h e g er m in al v e sicle (P h ilpott

et al., 1991; M aeda et al., 1998) seem t o play th e k ey r ole t o decon den se sperm nu cleu s

an d for m th e m ale pr on u cleu s . In t h e pr esen t st u dy w e dem on st r at ed t h at t h e n u clei

fr om v ariou s species sper m at ozoa can decon den se an d for m t h e m ale pr onu cleu s in

p or cin e oocy t e s w h en t h ey w er e inj ect ed . T his r esu lt ex t en ded in t h e pig t h e pr ev iou s

su cces sfu l pr onu clear for m at ion in m ice or h am st er oocy t es follow in g inj ection of h um an ,

pig , s ea ur chin or fish sper m at ozoa (Y an agida et al., 1991, W ak ay am a et al., 1997,

Kim ur a et al., 1998 ). In t h e pr esen t st u dy t h e form at ion of m ale pr onu cleu s h a s only

b een ob ser v ed in t h e activ at ed oocy t es , su g g est in g t h at decon den sation an d pr on u clear

form at ion of sperm n u clei in th e oocy t e cy t opla sm is cell cy cle dep en dan t . In h am st er

an d m ou s e oocy t es t h e act iv it y for t h e sper m decon den sation appear s aft er br eak dow n of

g er m in al v esicle, an d r each es a m ax im um at m et aph a se II an d disappear s follow in g

pr on u clear for m at ion (U sui an d Y an a gim a chi, 1976 ; U su i et al., 1997 ; M a eda et al., 1998).

Collect iv ely , m am m alian oocy t es s eem s t o h av e n on species sp ecific, cell cy cle dep en den t

abilit y t o decon den se sper m nu clei.

Dur in g conv ent ion al fer t ilizat ion , on ce m ale an d fem ale pr on u clei ar e in close

pr ox im ity , t h e nu clear en v elop s disper se, allow in g int er m ix in g of t h e chr om osom e .

D espit e of h ig h per cen t a g e of app osit ion of pr on u clei follow in g inj ection of for eign

species sp er m at ozoa , w e did n ot ob s er v e for m ation of sy n g am y or n orm al t w o cell

(17)

div ision in por cin e oocy t e s . Relat iv ely lit tle is k n ow n y et of th e det ail of for m at ion in

sy n g am y dur in g fer tilization . A ppar en t ly , t h e un ion of t h e m ale an d fem ale g am et e s t o

form sy n g am y s eem s t o b e con tr olled by species specific ch ar a ct erist ic s of th e oocy t e

cy t opla sm . F ur t h er st u dies ar e r equir ed t o iden tify fact or s in oocy t es affectin g pr onu clear

u nion t o for m sy n g am y follow in g inj ect ion of h om og en eou s an d h et er og en eou s

sper m at ozoa .

T his stu dy dem on st r at ed , for t h e fir st tim e, th at p or cin e oocy t es inj ect ed eit h er a

sper m at ozoon or an isolat ed sperm h ea d ar e capable of dev elopin g bla st ocy st s . A lt h ou gh

a few sh am inj ect ed oocy t es dev eloped t o th e bla st ocy st s , t h e in ciden ce of dev elopm ent

is v er y low . F ur t h er m or e t h e t im e r equir ed t o for m b la st ocy st s is m u ch lon g er t h an t h at

follow in g sp er m cell inj ect ion . T h e dev elopm en t t o t h e bla st ocy st follow in g sh am

inj ect ion is du e t o par t h en og en etic act iv ation . T h e low er in ciden ce an d delay ed for m ation

of bla st ocy st of par t h en og et ically act iv at ed por cin e oocy t es a s com par ed fer t ilized on e

h av e pr ev iou sly b een r epor t ed (Ch a et al., 1997 ; Kim et al., 1997b ).

. S U M M A RY

W e det er m in ed t h e in ciden ce of act iv ation , m ale pr on u clear for m at ion an d apposition

of pr onu clei in por cin e oocy t es follow in g int r acy t opla sm ic inj ection of v ar iou s por cin e

sper m com pon en t s an d for eign species sp er m at ozoa , su ch a s m ou s e, hu m an or cat tle.

T h e p or cin e oocy t e s w er e a ctiv at ed by inj ection of a sperm at ozoon or an isolat ed sp er m

h ead . N eith er isolat ed sper m t ail n or per in u clear m at er ial r em ov ed sper m h ead act iv at ed

(18)

oocy t es . Becau s e inj ection of m ou se , b ov in e or h um an sperm at ozoon act iv at ed por cin e

oocy t es , t h e sper m b or n act iv at ion fact or s is n ot st r ict species specific. M ale pr onu clear

form at ion an d pr onu clear apposition w er e ob ser v ed in th e p or cin e oocy t es follow in g

inj ect ion of por cin e , b ov in e , m ou s e or hum an sp er m at ozoa . T h e elect rical st im u lat ion

follow in g sp er m cell inj ect ion did n ot enh an ce th e in ciden ce of m ale pr on u clear

form at ion n or pr on u clear app osit ion com par ed w it h sper m cell inj ection alon e (P > 0.1).

M it osis an d t w o cell div ision in som e oocy t e s w er e ob ser v ed at 20 t o 24 h aft er

inj ect ion of por cin e sperm at ozoon . H ow ev er , n on e of oocy t es follow in g inj ect ion of

m ou s e, b ov in e or h um an sper m at ozoa dev elop ed t o th e m it otic m et aph a s e or n or m ally

div ided t o t h e t w o cell st ag e. T h es e r esu lt s su g g est ed t h at t h e oocy t e act iv at in g

fact or (s ) pr es ent ed in th e per inu clear m at er ial an d it is n ot species specific for t h e

p or cin e oocy t e.

. R E F E RE N CE S

B edfor d JM , Calv in HI : T h e occu rr en ce an d p os sible fu n ct ion al sig nifican ce of S - S

cr os slink s in sper m h eads , w it h part icular r efer en ce t o eut h er ian m am m als . J E xp Z ool

1974, 188, 137 - 156.

Ch a S K , N - H Kim , Lee HT an d Chu n g K S : P art h en og en et ic activ at ion an d dev elopm en t

abilit y of por cin e oocy t es tr eat ed w it h elect r ical stim ulat ion an d cy cloh ex im ide aft er in

(19)

v it r o m at ur at ion . R ep rod uction, F er tility and D e v e lop m en t 1997, 9, 441- 446

Kim N - H , S im er ly C, F un ah a shi H , S ch at t en G, D ay BN : M icr ot ub ule or g an izat ion in

p or cin e oocy t e s dur in g fert ilization an d p ar th en og en esis . B iol R ep rod 1996a , 54,

1397 - 1404.

Kim N - H , Chu n g , K S , Day BN : T h e r ole an d dist ribu tion of m icr ot u bule an d

m icr ofilam en t s dur in g fer t ilizat ion an d part h en og en esis . J R ep r od F er t 1997, 111,

143 - 149.

Kim ur a Y , Y an a gim a chi R , Ku r et ak e S , Bor t kiew icz H , P er ry A CF , Y an ag im ach i H :

A n aly sis of m ou se oocy t e a ctiv at ion su g g est s th e inv olv em ent of sper m p er in u clear

m at er ial. B iol R ep r od 1998, 58, 1407 - 1415.

Ku r et ak e S , Kim u r a Y , H oshi K , Y an a gim a chi R : F er tilizat ion an d dev elopm ent of m ou se

oocy t es inj ect ed w it h is olat ed sp er m h ead s . B iol R ep rod 1996, 55, 789- 795.

L ee JW , Kim N - H , L ee H T , Chu n g K S : M icr ot ubu le an d chr om atin or g anizat ion du r in g

t h e fir st cell cy cle follow in g int r acy t opla sm ic inj ect ion of r ou n d sperm at id in t o por cin e

oocy t es . M ol R ep r od D e v in p r es s , 1998.

M a eda Y , Y an agim achi H , T at en o H , U su i N , Y an agim achi R : Decon den sation of th e

(20)

m ou s e sper m nu cleu s w it hin in t erph a s e nu cleu s . Z y g ote 1998, 6, 39 - 45.

P ar rin g t on J , S w ann K , S ch ev ch en k o VI, S es ay A K , L ai F A : Calciu m os cillat ion s in

m am m alian eg g s t r ig g er ed by a solu ble sper m pr ot ein . N a t ure 1996, 379, 364 - 368.

P hilpott A , L en o GH , L a sk ey RA : S p er m decon den s at ion in X en opu s eg g cy t opla sm is

m ediat ed by n u cleopla sm in . Cell 1991, 65, 569 - 578.

P r ath er RS , Boice M L , Gib son J , H offm an KE an d P arr y T W : In v it r o dev lopm ent of

em b ry os fr om sin clair m iniat ur e pig s : a pr elim in ar y r eport . T he riog en olog y 1995, 43,

1001- 1007.

Ry b ou chk in A , Dozor t s ev D , D e S ut t er P , Quin C , Dh on t M : In tr acy t opla sm ic inj ect ion

of hum an sp er m int o m ou s e oocy t es : a u s eful m odel t o inv est ig at e oocy t e act iv atin g

capacit y an d th e k ay ot y pe of h um an sper m . H um R ep r od 1995, 10, 1130- 1135.

S u t ov sky P , H ew it son L , S im er ly C, T en g ow ski M W , N av ar a C, H a av ist o A , S ch att en

G : In tr acy t opla sm ic sper m inj ection for r h e su s m on k ey fer t ilizat ion r esult s in u nu su al

chr om at in , cy t osk elet al, an d m em br an e ev en t s , but ev en tu ally leads t o pr on u clear

dev elopm ent an d sp er m a st er a s sem bly . H um R ep r od 1996, 11, 1703 - 1712.

T esar ik J , S ou s a M , T est ar t J : H u m an oocy t e act iv ation aft er in t r a cy t opla sm ic sper m

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inj ect ion . H um R ep r od 1994, 9, 511- 518.

U sui N , Y an agim achi R : Beh av ior of h am st er sperm nu clei in cor por at ed in t o eg g s at

v ar iou s st ag e s of m atu r at ion , fer t ilizat ion an d early dev elopm ent : th e appear an ce an d

disapp ear an ce of fact or s in v olv ed in sper m ch r om at in decon den sation in eg g cy t opla sm . J Ultras tr uct R es 1976, 57, 276- 288.

U sui N , Ogu r a A , Kim ur a Y , Y an agim achi R : S p er m n u clear en v elope : br eak dow n of

int r in sic env elop e an d de n ov o for m ation in h am st er oocy t es or eg g s . Z y g ote 1997, 5,

35 - 46.

W ak ay am a T , U eh ar a T , H ay a shi Y , Y an ag im ach i R : T h e r espon se of m ou se oocy t e s

inj ect ed w ith sea u r chin sperm at ozoa . Z y g ot e 1997, 5, 229 - 234.

Y an ag ida K , Y an ag im ach i R , P er r eault S D , Klein feld RG : T h erm ost ability of sperm

n u clei a s se s sed by m icr oinj ect ion int o h am st er oocy t es . B iol R ep rod 1991, 44, 440- 447.

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