Production of fertile offspring from genetically infertile male mice

Area of Science:

• Reproductive Biology
• Genetics
• Developmental Biology

Background:

• Recessive autosomal genes can lead to male infertility.
• Mutations in genes like blind-sterile (bs/bs), quaking-sterile (qk/qk), and cyclic AMP responsive-element modulator (CREM) cause sterility in male mice.
• These genetic defects result in either no sperm production or abnormal sperm, and failure of spermiogenesis.

Purpose of the Study:

• To investigate the developmental potential of spermatozoa and round spermatids from male mice with specific infertility-causing gene mutations.
• To determine if genetic and epigenetic factors necessary for fertilization and embryonic development are present in these compromised germ cells.

Main Methods:

• Utilized male mice homozygous for the blind-sterile (bs/bs) and quaking-sterile (qk/qk) mutations.
• Studied male mice lacking the cyclic AMP responsive-element modulator (CREM) gene.
• Performed intracytoplasmic oocyte injection using spermatozoa or round spermatids from these infertile male mice into oocytes of normal females.

Main Results:

• Male mice with bs/bs, qk/qk, or CREM-null mutations were sterile due to severe defects in spermatogenesis.
• Despite sterility, spermatozoa and round spermatids from these mice successfully produced fertile offspring when injected into oocytes.
• This demonstrates that essential genetic and epigenetic components for syngamy and development are established before the final stages of sperm maturation.

Conclusions:

• Genetic mutations causing male infertility do not necessarily eliminate the potential for embryonic development from germ cells.
• Round spermatids and spermatozoa from infertile mice retain the capacity to support fertilization and early embryonic development.
• This finding has implications for understanding the precise genetic and epigenetic requirements for male fertility and potential therapeutic strategies.