Biomedical subjects

D Mahato

Publications and source records attributed to D Mahato.

3 recordsLinked to original sources

PubMed2001

Estrogen receptor-alpha is required by the supporting somatic cells for spermatogenesis.

The gene for estrogen receptor-alpha (ERalpha) was disrupted in embryonic stem cells by homologous recombination and these cells were used to generate mice with a targeted mutation in the ERalpha gene (alphaERKO mice). It was found that males homozygous for the mutation are infertile, indicating that estrogen signaling through this nuclear hormone receptor is required for male reproductive function. Although spermatogenesis appears normal in juvenile and young adult alphaERKO mice, the sperm produced are unable to fertilize eggs in vitro. To determine whether ERalpha is required by somatic or germ cells in the male reproductive tract, we transplanted germ cells from homozygous mutant (ERalpha(-/-)) males to the testes of wild-type (ERalpha(+/+)) males depleted of germ cells by busulfan treatment. The recipients ('surrogate fathers') sired offspring heterozygous for the mutation (ERalpha(+/-)) and carrying the coat-color marker of the infertile donor males. This indicated that ERalpha(-/-) germ cells are able to produce sperm competent to fertilize when they are supported by ERalpha(+/+) somatic cells. When ERalpha(+/-) offspring produced by germ cell transplantation were mated to produce ERalpha(-/-) males, these mice were found to have the same phenotype as originally reported for alphaERKO males. These studies showed that male germ cells do not require ERalpha for regulation of their own genes for development and function, and strongly imply that somatic cells of the male reproductive tract require ERalpha to support the production of sperm that are capable of fertilization.

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PubMed2001

Molecular mechanism of estrogen action in the male: insights from the estrogen receptor null mice.

Until recently, 17beta-estradiol was thought to be of little importance in male fertility. However, the descriptions of testicular dysfunction and behavioral deficits leading to complete infertility in male mice lacking estrogen receptor alpha (ERalpha) have indicated the importance of estrogen action in fertility of the male rodent. In contrast, male mice lacking the newly discovered estrogen receptor beta (ERbeta) exhibit no compromised fertility. Recently, elaborate sperm transplantation studies have shown that the altered sperm function characteristic of the ERalpha knockout male are the result of the loss of ERalpha actions in the supporting somatic cells of the testis and epididymis rather than in the germ cell. This brief review will discuss the roles of estrogen action in male reproduction as revealed by mice lacking both known forms of the ER. A brief review of the estrogen signaling system is also included.

Animals↗

PubMed2000

Spermatogenic cells do not require estrogen receptor-alpha for development or function.

Estrogen receptors alpha (ERalpha) and beta (ERbeta) are ligand-dependent transcription factors and members of the nuclear hormone receptor superfamily encoded by separate genes. Male mice homozygous for a mutation in the gene encoding ERalpha are infertile. To determine whether germ cells or somatic cells require ERalpha, germ cells were transplanted from donor males homozygous for the mutation (ERalpha-/-) to testes of wild-type (ERalpha+/+) recipient mice depleted of germ cells. The recipients served as "surrogate fathers" for the infertile ERalpha-/- males. When mated to wild-type females, the recipients sired offspring heterozygous for the mutation (ERalpha+/-) and carrying the coat-color marker of the ERalpha-/- donor mice. These studies show that male germ cells do not require ERalpha for development or to function in fertilization, and imply that male ERalpha-/- mice are infertile due to disruption of estrogen action within somatic cells of the male reproductive system.

Animals↗