The long term objective of this study is to determine what extragenetic factors the spermatozoon provides the ovum at fertilization. The mitochondrial microinjection technique we have developed will be used to define the role of paternal mitochondria during fertilization and early embryogenesis. A transgenic approach will be taken to elucidate why testicular mitochondria require a novel isozymic variant of the mitochondrial oxidative phosphorylation protein cytochrome c. DNA sequence and hybridiza- tion studies will be conducted to determine whether the mitochondria of the spermatozoon are programmed for non- proliferation and gossypol will be used as a molecular probe to investigate mitochondrial differentiation in the mammalian testis. These studies will help identify epigenetic and nuclear regulated processes that are essential for normal mammalian development. A better understanding of these events is necessary to explain how perturbations lead to birth defects. In addition, a more detailed comprehension of the biochemical events at and following fertilization will provide necessary information to aid in the treatment of the infertile and may provide superior approaches to fertility control.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
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Reproductive Biology Study Section (REB)
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Tufts University
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Syed, V; Hecht, N B (2002) Disruption of germ cell-Sertoli cell interactions leads to spermatogenic defects. Mol Cell Endocrinol 186:155-7
Syed, V; Hecht, N B (2001) Selective loss of Sertoli cell and germ cell function leads to a disruption in sertoli cell-germ cell communication during aging in the Brown Norway rat. Biol Reprod 64:107-12
Chennathukuzhi, V M; Lefrancois, S; Morales, C R et al. (2001) Elevated levels of the polyadenylation factor CstF 64 enhance formation of the 1kB Testis brain RNA-binding protein (TB-RBP) mRNA in male germ cells. Mol Reprod Dev 58:460-9
Syed, V; Gomez, E; Hecht, N B (1999) mRNAs encoding a von Ebner's-like protein and the Huntington disease protein are induced in rat male germ cells by Sertoli cells. J Biol Chem 274:10737-42
Syed, V; Gomez, E; Hecht, N B (1999) Messenger ribonucleic acids encoding a serotonin receptor and a novel gene are induced in Sertoli cells by a secreted factor(s) from male rat meiotic germ cells. Endocrinology 140:5754-60
Syed, V; Hecht, N B (1998) Rat pachytene spermatocytes down-regulate a polo-like kinase and up-regulate a thiol-specific antioxidant protein, whereas sertoli cells down-regulate a phosphodiesterase and up-regulate an oxidative stress protein after exposure to methoxyethanol and met Endocrinology 139:3503-11
Gu, W; Hecht, N B (1997) The enzymatic activity of Cu/Zn superoxide dismutase does not fluctuate in mouse spermatogenic cells despite mRNA changes. Exp Cell Res 232:371-5
Yiu, G K; Murray, M T; Hecht, N B (1997) Deoxyribonucleic acid-protein interactions associated with transcriptional initiation of the mouse testis-specific cytochrome c gene. Biol Reprod 56:1439-49
Yiu, G K; Hecht, N B (1997) Novel testis-specific protein-DNA interactions activate transcription of the mouse protamine 2 gene during spermatogenesis. J Biol Chem 272:26926-33
Choi, Y C; Aizawa, A; Hecht, N B (1997) Genomic analysis of the mouse protamine 1, protamine 2, and transition protein 2 gene cluster reveals hypermethylation in expressing cells. Mamm Genome 8:317-23

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