How Sperm Meets Egg: A Mystery Unravels

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Consider the challenge faced by a human sperm cell. The tiniest cell in the human body, it must navigate the equivalent of dozens of miles through an obstacle-strewn maze to find the egg.

Two new papers published in Nature on March 16 reveal for the first time a key part of the process, and the findings could lead to new treatments for male infertility and to new methods of contraception. (More on Stress Doesn’t Hurt Chances of Success with IVF)

Researchers have known for years that the hormone progesterone is somehow involved in getting sperm to meet egg. It is assumed that sperm are attracted to higher concentrations of progesterone, which is released by the egg and is found in higher levels closest to it. But how exactly the hormone activates sperm has remained a mystery.

The new research reveals part of that answer. Scientists at University of California, San Francisco, and the Center of Advanced European Studies in Bonn, Germany, used a new technique to study individual sperm cells. They already knew that exposure to progesterone rapidly affects sperm cells and allows calcium to enter them, ultimately causing sperm to wave their tails ferociously in a process called hyperactivation — an “extravagant” activity, as the Nature paper describes it.

The mystery has revolved around how progesterone causes this extravagance — which is, of course, necessary for conception. Progesterone is known to work by affecting gene transcription in cells, but since transcription doesn’t occur in sperm, that isn’t the answer here. The secret, instead, appears to involve a protein called CatSper discovered in 2001 and found only in the tails of sperm. (More on Women With Circumcised Partners May Have Lower HPV Risk)

The new studies found that stimulating CatSper had the same effect on sperm tails as progesterone, and that blocking the protein sharply reduced — but did not entirely eliminate — progesterone’s effect.

The fact that blocking CatSper did not completely prevent progesterone from influencing sperm activity means that there’s more to this story. But understanding the CatSper mechanism alone could potentially help treat some cases of male infertility, which mutations in the CatSper gene are known to cause.

Further, figuring out how to block CatSper could contribute to the development of new forms of birth control. (More on An IUD May Treat Endometrial Cancer and Preserve Fertility in Young Women)

Whatever the ultimate outcome, it never ceases to amaze me how complicated human reproduction is — and that it often actually works!

[h/t: The Scientist]