8
臌腴腶腧腹腲膀膇臚膌膪膱 Vol. 33, pp. 279286, 2005 MATERNALP5 腃腇腅腆腌腉腋腂腀腁腄腈腊 腓腗 12 腈腃 腐腄 腊腖 腃腍 腘腄 1 腋腑 腄腍 腂腈 12 腝腣膋 1 腃腉 腏腆 腔腙 腕腃 1 Andrea Jurisicova 2 Robert F. Casper 2 : 17 8 18 MATER maternal antigen that embryo require῍ῒNALP5 腘臰腽臩腘臹膠腎腤臟臸 腕腁腣Mater ΐῒΐ 膲腴腨腭腙臼膠膗腙臗腉腚臉臃腕腁腤腟腙腙腐腙膹臋2 膐腕臹 膂腇臦膯腍腔腍腝腃膧膕MATER 腵腰腫腹腱腶腧臱腕臹膠腍腔腂腤腋腖腇膶腌 腥腑腇腐腙膑臶腚腁腎腕腁腤腐腋腕Mater ΐῒΐ 腴腨腭腙腵腰腫腹腱腶腧膑臶腦膊 臎腎腤腋腖腘腡腒腔MATER 腵腰腫腹腱腶腧腘腅腂腔膑臶腍腔腂腤膆臶臇腦膛臯 腍腑812 Mater ΐῒΐ 膒腜 Mater wild type WT膲腴腨腭腙腵腰腫腹腱腶腧腙 臬腻膎臇膎臇膬臓 ROS膎臇腪腷腮腯腩腹臵臭腦臖臧腍腑Mater ΐῒΐ 腙腵腰腫 腹腱腶腧臬腻膎臇腚 Mater WT 腡腣腟腼腘膥腆腒腑腵腰腫腹腱腶腧腘腅腊腤 ROS 膎臇腚 Mater WT 腡腣腟 Mater ΐῒΐ 腕膥腉腪腷腮腯腩腹臵臭腚 Mater ΐῒΐ 腕臥腂膖膣 腘腁腒腑腺臂腙膙膈腆腢Mater ΐῒΐ 腕腚腙腵腰腫腹腱腶腧臙膸腇腽臃腘臅腍腑 膙膈膎臇膬臓腇臢臐腎腤腇腪腷腮腯腩腹腇膟膿腍腔腂腤腑腞膎臇膬臓腦膊腕腈腏臷臞腦腈腑腍膨膰腇臕臅腌腥腤腖膤腄腢腥腤腝腑MATER 腚臉臃腗臹臊臰腘膐膾膐腘腅腂腔臻腗臟臸腕腁腤腇膹臋腺臒腙腘腅腂腔膩腍腔腂腤膆臶臇腇膶膦腌 腥腤ῐῌ῏ MATERNALP5腵腰腫腹腱腶腧膎臇膬臓 Maternal antigen that embryos require MATER腴腨腭腘腅腊腤臔臹premature ovarian failure: POF臘膊腙膉臨腕臹膝腌腥腇臉臃腗臄臘腦腾膳腎腤腑腞腘臻腗臟臸腕腁 1MATER 臟臸腚膕至臹膝腌腥腑 NALP pro- tein family 腙膃腓腕腈腍 NALP 5 腖腟膡腛腥腔 腂腤 2῏ΐ3腋腥腝腕腙膜膓腕NALP protein family 腧腳腰腀腬腭腠膄臀臺膅腙腬腪腲腷自臜腘膏腍腔腂腤腋腖腇臡腢腥腔腂腤 4῏ΐ9MATER 腘臰腽臩腘臹膠腎腤臟臸腕膃膵腓腊腙膴膐腡腣臹膠腍膾膐 blastocyst 腝腕膛 膼腌腥腤 10Mater mRNA 腚腴腨腭腕腚膞 腓腊腡腣臹膠腍膃膵腓腊腕膧膥臠腖腗腤腇腙膢腚腓腊臹膂腖腖腟腘膟膿腍膹臋膢腙 24 膐腘腚膛膼腌腥腗腉腗腤 10Mater ΐῒΐ 膲腴腨腭腆 腢膫臊腌腥腑膹臋腚臛膃膍腎腤腟腙腙2 膐腕臹膂腇臦膯腍腔腍腝腃 2-cell block112 膐腕臹臊腇臦膯腎腤膠臁腚Mater 1 臌腴腶腧腹腲膀膇臚膌 臆膇膌膔膷 2 Samuel Lunenfeld Research Institute SLRI, Mt. Sinai Hospital, 腰腸腹腰臚膌膫臆膇膌膔膷 279 63

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Page 1: MATER NALP5 - St. Marianna University School of Medicineigakukai.marianna-u.ac.jp/idaishi/www/334/08-33-4Chiharu Tuda.pdfH Q= H < MATER RS8TU V 2 9 MATER 1 ! /22W3X Y 9 Z[. \]3 &

� � ����������Vol. 33, pp. 279�286, 2005

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���1 Andrea Jurisicova2 Robert F. Casper 2

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� �MATER �maternal antigen that embryo require��NALP5 $�%�&'()&*+,-./01�� Mater ��� 2�3456+7589$:;01-<55� =5�>�$ 2%�?0*@ABCDED�F� GH� MATER A�%�IJK�L���0*+DEM-NOAPQRSA� =5TU$�01-� =N0� Mater ��� �34�%�5IJK�L��TUVWX,-NO&YZE� MATER A�%�IJK�L��&[METUDEM-\U]V^_DS� 8�12`5Mater ���abMater wild type �WT�2�345�%�IJK�L��5�cde]� e]fg �ROS�e]� hijkl�mnVopDS� Mater ����%�5IJK�L���cde]$ Mater WT Y�<�q&rsZS� �%�IJK�L��&[t-ROS e]$ Mater WT Y�< Mater ��� 0r9� hijkl�mn$ Mater ��� 0uMvw&1ZS� xy5z{s|� Mater ��� 0$� �%�5IJK�L��}~A(;& �DSz{� e]fgA��,-A� hijkl�A��DEM-S�e]fgV�W0��� %���V�SD%��A��QR-O��|R-� �S� MATER $:;��*�� '&��?�?&[ME���./01-A� �>x�5�%�&[ME��DEM-\U]AP�QR-�

����MATER� NALP5� �%�� IJK�L��� e]fg

Maternal antigen that embryos require �MATER�$� �34&[t-�*�� �premature ovarianfailure: POF� 5��W5��0*�QR� �%�A:;���V��,-S�&���./01-1�� MATER ./$H!*�QRS NALP pro-

tein family 5��0� �� NALP 5 O<� RE

M-2��3�� NR�05¡¢0� NALP protein family$� �£J¤¥4¦§¨©ª5¥h�i«¬&­�DEM-NOA®|REM-4��9��MATER $�%�&'()&*+,-./0�

�¯��5°?Y�*+D� �? blastocyst�0^±QR-10�� ��� Mater mRNA $�340$²³��Y�*+D� �¯��0Gr´O�-A� =5µ$��*@OO<&��D� �>µ5 2�4%�?&$^±QR�9�-10�� Mater ��� 2�34s|¶�QRS�>�$·���,-<55� 2%�?0*@ABCDED�F �2-cell block�11�� 2%�?0�*�ABC,-+¸$� Mater � 5�%�

1 �������� ¶�¹�º»2 Samuel Lunenfeld Research Institute �SLRI�, Mt.Sinai Hospital,

J¼�J¶�¹�º»

279

63

Page 2: MATER NALP5 - St. Marianna University School of Medicineigakukai.marianna-u.ac.jp/idaishi/www/334/08-33-4Chiharu Tuda.pdfH Q= H < MATER RS8TU V 2 9 MATER 1 ! /22W3X Y 9 Z[. \]3 &

� Mater ������������� ���Figure 1�� ���� �����������MATER ����������� �!��"�#$%�&'���� (� MATER )����*$+,�!��"-� MATER �./�0������*$�12345� 2��������678����3�9 �NALP protein family �:;)� <;*$�=�

��>>"��� MATER �?3�) (@��9A�: � BC� MATER )����DEF��G3� D�HIJKLMN�O�PQ8���R��10��S��� �TU�)� MATER )�8�V�

������� �*$3� �#$%�"��WX� ���Y�HIJKLMN*$�> �Z[3�

�����

�� ����� ��Dr. Larry Nelson �NICHD � NIH� Bethesda,USA���Mater +��\ B6A �C57BL�6J�A�J� F1 ]^_�`��� Samuel Lunenfeld ResearchInstitute animal facility �Toronto, Canada� �abc+,3� ����]^_cdefg�h� Ma-ter wild type �WT��Mater ���\]^_cij�k�3� lm�=n)� opqr0-st3DNA �High Pure PCR Template Preparation Kit,1�796�828, Roche, USA ck�� �� PCR �c� �u�� PCR primer )� Mater WT ) sense

� 5’-TCA TGT CCT TGG ATG GCA TG-3’�antisense � 5’-CCA CGT GCT TTC AAG ATTGC-3’c� Mater ���) sense� 5’-ACC GGT GGATGT GGA ATG TG-3’� antisense � 5’-CCA

CGT GCT TTC AAG ATT GC-3’c� � PCR)� 95�C 5 c 1 vwxy� 95�C 30 z� 59�C 30z� 72�C 1 c 37vwxy�{|�3� 1.25�Agarose gel �}~��3� Ethidium bromide so-lution����� Mater WT) 396 bp, Mater ���)242 bp, Mater +�� )�������KLc��3������)� Samuel Lunenfeld Research In-stitute animal facility ���232�C�� ��652��� ����5 : 00�17 : 00����� �����Purina Mouse Chow� ��)���X���3� ������ij)� Mount Sinai HospitalAnimal Care Committee �����������u���� ��8�12��� Mater WT, Mater ��� \]^_������%%����y�K �pregnant mare’s se-rum gonadotoropin: PMSG� �NHPP, NIDDK, Dr.A. F. Parlow��`� 5 IU� 48 ¡��¢I��%%����y�K �human chorionic gonado-toropin: hCG� �Wyeth, Canada� 5 IUc�£¤¥3� 12  ¡���¦c§t3� ¨�� ©�ª�200 mlY�� 26G«¬­��¦�®�c¯°3��±���²-³(����c´µ�3��� ©�ª�3� 0.5� bovine serum albumin �BSA;

Figure 1. Maternal lethal e#ect. The embryo of F1 Mater ��� becomesarrested during early stages of development. Therefore, there is

no o#-spring produced �F2 less mutation�.

¶·¸¹ º»¼´� �280

64

Page 3: MATER NALP5 - St. Marianna University School of Medicineigakukai.marianna-u.ac.jp/idaishi/www/334/08-33-4Chiharu Tuda.pdfH Q= H < MATER RS8TU V 2 9 MATER 1 ! /22W3X Y 9 Z[. \]3 &

Sigma, Canada���� modified human tubal fluidmedium �mHTF; Irvine Scientific, USA� ������ �� 0.3 mg�ml hyaluronidase ����� ��� 1���� �������������� ��!"�#$%&'(�)'(*+�,�-�.� 0.5� BSA ��� mHTF �����/0�� )1'(�2345��)�67����12���� ��� fragmentation �Mater WT8Mater ������9)'(�� 0.5�

BSA ��� human tubal fluid medium �HTF ;Irvine Scientific� USA� ��:� 37�C� 5� CO2� ��� ;)<�0 <=�� 24 <=.� 48 <=.'(>9 fragmentation �?@�#� A9BCD�EB����� �������� ����a� F�GHIJK&LMNOPQDePsipher �DePsipherTM Kit� TA700 ; R&D Sys-

tems Inc., USA� 0.5 ml, HTF 890 ml, reaction bu#er

100 ml, stabilizer 10 ml �RS�#� 30�= 37�C�THU"VW!XH��� Y� 13,000 g # 1�=Z[�,�� �\9]� DePsipher ��8�#����� ;^�� Mater WT� Mater ��� 9)'(�� DePsipher ��:� 37�C� 5� CO2 �25�= ���� 0.5� BSA��� mHTF ��� 1 �/0��.� _�` ��a�#bc�de�� Y� deconvolution microscope �Olym-pus IX70; Applied Precision Inc.�USA��)'(�?@��� f98g� hijk�lmn J-aggre-gate 8oijk�lmn J-monomer �ApqpRITC �rhodamine isothiocyanate�8 FITC �fluore-scein isothiocyanate� rstW��`#uB���f9vw�x� yzF�GHIJK� J-aggregate{uB�pn{� &LM{|}��F�GHIJK�xfp{uB�p~`� J-aggregate 8 J-mo-nomer 9�S� Delta Vision Software �AppliedPrecision Inc.� USA� ��`#���� J-monomer�mn J-aggregate 9�S�F�GHIJK&LMNO8]~���b� ROS �Reactive oxygen species� NOPQDimethyl sulfoxide �DMSO; Sigma� Canada�

990 ml 8 2’,7’-dichlorodihydrofluorescein diacetate�H2DCFDA� �Molecular ProbesTM; Invitrogen�USA� 10 ml�RS�� fp �1mMH2DCFDA��j

ki�8�#�`�� ;^�� Mater WT, Mater��� 9)'(�� 0.5� BSA ��� HTF 1ml jki� 1 ml����� ��:�� 37�C� 5� CO2� 15�= ���� deconvolution microscope �FITC rstW����#�p���� DeltaVision Software �bcmnf8*e# ROS NO�Q�����c� �st��HPQ;^�� Mater WT, Mater ��� 9)'(��HTF�0.5� BSA 988 ml H2O 11.4 ml����� ��:� 37�C� 5� CO2 � 90�= ���� �{��mn 15�� ��: monochlorobi-mane � 1 ml���#)'(F�GHIJK�9�st��H��i��� deconvolution microscope� CFP rstW��`#�p���� DeltaVision Software �bcmnf8*e#�st��H��Q������ ��������x���������� 2�=�9u�x

c2uQ �Fisher’s exact test��`# p0.05��e# ¡�¢+8£Q���

� �

�� ��� fragmentation �)'(9'(> fragmentation Dx� ;)<�0<=�xMater WT 4.151.92�� Mater ��� 1.060.76�� 24<= �.x Mater WT 8.126.53��Mater ��� 2.431.62�� 48 <= �.x MaterWT 64.606.49�� Mater ��� 68.769.18��¢+� ¤�=��x¥p~¦e� �Figure 2���� �������� ����a� F�GHIJK&LMNO)'(F�GHIJK9&LMNOx� MaterWT �x 0.740.05� Mater ��� �x 0.950.10�¢+� Mater ���9)'(3§�xMater WT *+� ¡¨��©�� �p0.02� �Figure 3��ª�� Mater WT �x J-aggregate x)'(9«¬­®�#`�9��� Mater ��� �x)'(3§¯®�#`� �Figure 4��b� ROS �Reactive oxygen species� NOPQ)'(�°n ROS NOx� Mater WT �x74.9923.39�105� Mater ��� �x 110.147.91�105 �¢+�  ¡�x~¦e�{ Mater ��� �xMater WT *+�¨`±²¢e� �Figure 5��

MATER 9)'(�°n³´ 281

65

Page 4: MATER NALP5 - St. Marianna University School of Medicineigakukai.marianna-u.ac.jp/idaishi/www/334/08-33-4Chiharu Tuda.pdfH Q= H < MATER RS8TU V 2 9 MATER 1 ! /22W3X Y 9 Z[. \]3 &

0

0.2

0.4

0.6

0.8

1.0

1.2

Mitochondrial membrane potential

in oocyte 

WT -/-

P<0.02

  

 

Mater WT ����������� ROS �������� Mater ��� ��������������� �Figure 6��c� ����� !"#��$%&'����� (�� Mater WT�166.30�9.25�107� Mater ��� � 113.59�1.98�107

�)*� Mater WT��Mater ��� +*,-.$�(/01� �p�0.01� �Figure 7��

� �

MATER�NALP5�� NALP protein family23�#���4$567'89�)'� NALP pro-

tein family �:;<=>?� Pyrine domain

�PYD-�, NACHT domain� @�ABC=� Leuci-ne-rich repeats �LRRs-� �DEFGH/-1� :IJKCLMNOPQ�C�R�ST$UV1��'�W�XYZ��'4��9�� [\L�Nalp]S^�_`� Nalp 12, Nalp alpha, Nalp beta, Nalp

gamma, Mater�Nalp 5, Nalp delta, Nalp epsilon,Nalp zeta, Nalp eta, Nalp theta � Chromosome 7Aa$bc1� Nalp iota, Nalp 10� Chromosome7F a$bc1�%*� Mater�Nalp5 �d� Nalp

]S^Wef�gh$ij1�bc1��'2��kl 2�4m�[\L�no/pq7'W� rstu��#vN/��1�w5xy �premature ovar-ian failure: POF�WF'13��16��� [\LMATER��� POF z{�[\L�#v�G|$561�

Figure 2. Spontaneous cytoplasmic fragmentation �FR�rate in oocytes. There was no statistical

significant di#erence in spontaneous cyto-

plasmic fragmentation rate between Mater WT

and Mater ��� oocytes. In WT, 0hr: n232,24hr: n84, 48hr: n73. In ���, 0hr: n461,24hr: n89, 48hr: n60.

Figure 3. Mitochondrial membrane potential in oocytes.

There was a significant di#erence between

Mater WT �n19� and Mater ��� �n20� inoocyte mitochondrial membrane potential

�p�0.02�.

Figure 4. Images of oocytes stained with DePsipher.

J-aggregates �red� were localized to the outerregion of the Mater WT oocyte. However,

J-aggregates were distributed all over the

oocyte in Mater ���.

Figure 5. ROS activity in oocytes. ROS activity in

Mater ��� oocytes �n45� was higher than thatin Mater WT oocytes �n28�, although therewas no statistical di#erence.

}~�� ���2� Y282

66

Page 5: MATER NALP5 - St. Marianna University School of Medicineigakukai.marianna-u.ac.jp/idaishi/www/334/08-33-4Chiharu Tuda.pdfH Q= H < MATER RS8TU V 2 9 MATER 1 ! /22W3X Y 9 Z[. \]3 &

����������� �1�� MATER �������������� Mater ��� ���������������� Mater ��� �����!"��#�$%�&'� (�)*+,-�� �.�� �����/ Mater WT ����0���10�1� Mater ��� ���234�� �����56�78�/��� 29�����1:;<=�> ��&�11�� Mater +�� ��� ?(��@��� F1 AB� Mater ���� ������� 14�� �1� F1� Mater ��� ����Mater WT ����?(��@� Mater +�� �CDE"?/F���?G��/� H�������I���JK���1:;<=�>� 4L?4��M&�� H ? F2 NO�P�$��=�Figure 1��H�Q=�� H <�� MATER ���������RS8TU��V� ��� 2� �9�� MATER 1�!���/22W3X� Y

��9��Z[�.��\]3 �&�� <��MATER ��9��^_`�abc��!��10�� YH�� de�Mater ���� Mater WT ����^_`�abc.�?�f8�H��Qg�MATER ��9�^_`�abc�Z[�.�?h�8�H�?�i���<X� �9��^_`�abcj,�k��6F�� Y��lm?\]�� H�no�p��DePsipher�q�r�,��st�,uv �5, 5’, 6,6’-tetrachloro-1, 1’, 3, 3’-tetraethylbenzimidazolyl

carbocyanine iodide� �� 6��cw_xy��z{��|�^_`�abc�lm�}~?��8���p�� �19��21�� DePsipher �� �%&�lm?����^_`�abc��_b�������< ��� �u�� �J-aggregate� ?�8�� �g� �u��?�8�^_`�abc�j,���H�?�8� 6�� �lm?}~�^_`�abc������< X� 9�����u�� �J-monomer� ?�8�� H���� DePsi-pher �^_`�abc������< &�1�^_`�abc�-����8�������>��u�����i��lm?}~�^_`�abc?�8���3 �� Figure 3 ���Q=��Mater WTQ�/Mater ��� �^_`�abcj,1 ���� �9���� ^_`�abc�B�j,+�v}!"� �B��������# � Z�� �����$z{�H 3�¡�� ��'21��22�� 2� Mater ��� ���9��JK�8��^_`�abcj,1$%� ���H�1%¢£�Q��32�&g�� H ��MATER 1^_`�abcj,?�¤�@�.�?&8�H�?�¥8�� <�� Mater WT��j,��^_`�abc1�9��¦§�¨©������ Mater ��� ���9�ª«�¬©��� H �� Mater WT�^_`�abcj,1 ­� ��1� Mater ��� �^_`�abc?j,�8� ­.�1�¤��H�?�8�2/ &��^_`�abc�9���Z[�j,�v�®�&��¯�&g��1� H�j,�v�DNA+°'�� q�&±?²³� 9�´?(µ8�23��H�¢£�Z[� ROS ¶·�¸¹��� &º»��3 &2g�1Mater ����Mater WTQ�/¼�����g�� �g� Mater ��� ��9��

Figure 6. Images of oocytes stained with H2DCFDA.

ROS activity were more concentrated in the

centre of the oocyte in Mater WT, but they

were spread around the cytoplasm in Mater

���.

Figure 7. Glutathione level in oocytes. Glutathione

levels in Mater ��� oocytes �n�46� were sig-nificantly lower than in WT oocyte �n�34��p0.05�.

MATER ��9��Z[�.� 283

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�� ��������� ������� �������������� ����� �!"��#�$� 2#�%&����'(�)'�*+� �#�&� ROS ����� MaterWT � Mater ��� &��,'� -*.� Mater WT&� ROS ��#�� /�&01�+��2�� Mater ��� &��#�34&56��7+� 6����89���&)'�� (�:-���� �#��;<07=>&?@A'��BC��7'�1D��,7�EFGHI����J���K������L�+M�NO;<PQA'�R�)'23��24���ST���� �#��UV'EFGHI�W�Mater ����U7�Mater WT �.D�8��X��7+� Y��� Mater ���&�Mater WT �.D���PQ��X��7'�Z[��'��ST&� 8�12\��]^_<`��+�� 6�a��#� fragmentation ��� Mater WT �Mater ��� &b�ca�,1�+d1a� 6�\�&��#��e�?@���7'd�fg��'� �1�� �#���������e<�hA'�� Mater ��� ]^_��#���������������U.� ���� ����L��ij�� �a�EFGHI��L��X��7'+k�� ��<PQA'���XA'6��fg��'� li���1a� Mater ��� ]^_��#���������m�� �������#��;��X)'7�#�$�����'�noa�'� ip�+�q�� Mater ��� ]^_�!"�� 2#�%&��<�rA'6���a��7'11��� 6� 2-cell block ���es���&)'� �ST&�� Mater ��� �#��;��X��7'+k� ��� 2#�%&�rA'(<�A'6�� MATER ��#����������EFGHI��L<07=>&?@A'e<��� *+� �������!"t<�X�u'6�<fg�+�vw� ]^_ Mater x#y�z{i|}~���07x#y���&$%��� 6�x#y�e������7'25�� ��� MATER�NALP5 ��a��#,e���vez����� ������&�J��'������J�(��R��)A'�noa�'�

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��<�o'�)+.� ��f� ���<�.*�+�]�����������(��G� *¡¢£�,a���+¤�0¥¢¦ST§�¨�©ª7+�*A� *+� ST�«<)o�7+¬R� ��,'�­����®¯_<7+¬R*�+ SLRIDr. Casper�Brown Lab �°,�©ª7+�*A��ST�:�� 25th Great Lakes MammalianDevelopment Meeting �2005- 3±; Toronto, Can-ada�� ² 57³.���+¤��´�µ¶·´�2005- 4±; ¸/��U7��0�+�

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1� Tong ZB, Nelson LM. A mouse gene encodingan oocyte antigen associated with autoimmune

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Abstract

Role of MATER�NALP5 in Oocyte Mitochondria

Chiharu Tsuda1�2, Juichiro Saito1, Asako Taniuchi1�2, Marie Ino1,

Bunpei Ishizuka1, Andrea Jurisicova2, and Robert F. Casper2

Maternal antigen that embryo require �MATER� was identified as a possible factor inducing prematureovarian failure in mice. MATER, also known as NALP 5, belongs to the NALP protein family. Despite the

known domain structure of this protein, nothing is known about its function. In contrast to other NALP

family members, MATER is exclusively expressed by germ cells during oogenesis as well as by early cleaving

embryos. Female mice lacking functional Mater gene are infertile due to early embryonic arrest at 2-cell

stage, followed by cytoplasmic fragmentation. Recent studies suggest that MATER localizes to mitochon-

dria and nuclear envelope of oocytes. Therefore, we hypothesize that MATER functions as an anti-apoptotic

protein, and that disruption of Mater gene leads to altered mitochondrial function and accelerated ovarian

aging. Spontaneous cytoplasmic fragmentation of ovulated oocytes was not di#erent between Materwildtype and ���. Analysis of cellular parameters in ovulated oocytes lacking Mater revealed a significantincrease in mitochondrial membrane potential accompanied by increased accumulation of reactive oxygen

species �ROS� and decreased glutathione content. These results demonstrate that Mater decrease mitochon-drial membrane potential and ROS production. Furthermore, it is suggested that oocyte quality is impaired

in the Mater null females, leading to failure of early embryo development via alteration of mitochondrial

activity.

1 Department of Obstetrics and Gynecology, St. Marianna University School of Medicine, Kawasaki, Japan

2 Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto, Ontario, Canada

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