Epididymal hypo-osmolality induces abnormal sperm morphology and function in the estrogen receptor alpha knockout...

Area of Science:

• Reproductive Biology
• Endocrinology
• Spermatogenesis

Background:

• Estrogen receptor-alpha (ESR1) is crucial in male reproductive tract function, particularly in efferent ductules and epididymis.
• Male mice lacking ESR1 (Esr1KO) are infertile, with germ cells capable of fertilization only in a wild-type environment.

Purpose of the Study:

• To investigate the impact of an altered epididymal microenvironment on sperm morphology and function in Esr1KO mice.
• To determine if the infertility in Esr1KO males is due to intrinsic defects in sperm or extrinsic factors within the reproductive tract.

Main Methods:

• Sperm morphology was assessed in different regions of the epididymis in Esr1KO and wild-type mice.
• Epididymal fluid composition, including osmolality, was analyzed.
• Esr1KO sperm were incubated in a modified osmotic environment to assess functional rescue.

Main Results:

• Sperm from Esr1KO mice exhibited abnormal flagellar coiling and increased spontaneous acrosome reactions.
• Epididymal fluid in Esr1KO mice showed reduced osmolality, indicating impaired fluid absorption.
• Morphological defects worsened with sperm transit through the epididymis, and altered osmolality partially rescued flagellar coiling.

Conclusions:

• The infertility in Esr1KO mice is primarily caused by an abnormal luminal fluid environment in the efferent ductules and epididymis.
• This altered environment disrupts normal sperm maturation, leading to progressive sperm deterioration and infertility.
• Restoring a more physiological osmotic balance can partially ameliorate some sperm defects.