Live offspring from mice lacking the Y chromosome long arm gene complement

Area of Science:

• Genetics
• Reproductive Biology
• Mammalian Genetics

Background:

• The mouse Y chromosome long arm (Yq) contains repetitive DNA (non-PAR region, NPYq) essential for male fertility.
• Deficiency in NPYq genes impairs spermiogenesis, leading to subfertility or infertility.
• Specific mouse models, like XSxr(a)Y*(X) (NPYq- males), exhibit Yq-gene deficiency and sperm defects.

Purpose of the Study:

• To investigate sperm function in NPYq-deficient mice using intracytoplasmic sperm injection (ICSI).
• To assess the role of NPYq-encoded genes in fertilization and early embryonic development.
• To develop a novel mouse model for studying Y-encoded gene functions.

Main Methods:

• Intracytoplasmic sperm injection (ICSI) was performed using sperm from NPYq-deficient mice.
• Offspring were analyzed using Xist RT-PCR genotyping and karyotyping.
• In vitro fertilization (IVF) was used as a comparative fertilization method.
• A new NPYq-deficient mouse model was established.

Main Results:

• ICSI resulted in liveborn offspring from NPYq-deficient sperm, with successful identification of all predicted genotypes.
• NPYq-(2) males, possessing the same Y gene complement as NPYq- males, showed infertility and malformed sperm heads.
• Sperm from NPYq-deficient males successfully fertilized oocytes via ICSI but failed in IVF.
• NPYq-encoded gene functions are not essential for post-penetration events within the oocyte.

Conclusions:

• NPYq-encoded genes are crucial for natural fertilization (IVF) but not for ICSI-mediated fertilization.
• Yq-encoded gene functions are not required after sperm entry into the oocyte.
• The developed NPYq-deficient mouse model is a valuable tool for future research on Y-chromosome gene function and male infertility.