Sperm have a heat-activated switch that may be key to fertility

Mammalian sperm are unusually picky. They prefer cooler environments, thriving below normal body temperature. Yet, they must navigate the female reproductive tract, which is warmer. So how do they survive and succeed?

New research from Washington University School of Medicine in St. Louis explains how. Sperm use the temperature difference as a signal.

When they enter the warmer female reproductive tract, they switch behavior. They move from calm, forward swimming to a vigorous, whip-like thrash. This change helps them pierce the egg for fertilization.

This discovery sheds light on male fertility. It also opens new directions for contraception.

Heat flips a sperm switch

All mammals carry a sperm-surface protein called CatSper. It regulates ion entry, powering the tail’s strong motions. Scientists found that temperatures above 38°C (100.4°F) activate this protein.

“That hyperactive state in sperm is key for successful fertilization, and no one knew exactly how temperature triggers it,” said Polina Lishko, PhD, professor of cell biology and physiology at WashU Medicine.

“Our work has identified a temperature-controlled switch in sperm that triggers these increased movements precisely when they are needed during fertilization.”

Before this study, CatSper was thought to respond only to pH and progesterone. But most mammalian sperm ignore progesterone. Temperature turns out to be the real switch.

This change explains why testicles hang outside the body. Evolution keeps them cool so sperm remain inactive until they reach warmer territory – then, they activate at just the right moment.

Mammals evolved to keep sperm cool

Humans aren’t the only species with clever cooling tricks. Dolphins pass blood through their dorsal fins to cool it before it reaches their testes. Elephants do the same through their ears. These adaptations protect the sperm’s sensitivity.

Birds, which lack CatSper, don’t need this. Their sperm do not rely on the same activation signal. This protein, and its temperature-based switch, is unique to mammals.

Using advanced tools, the researchers watched electric charges shift inside individual sperm. When exposed to higher temperatures, CatSper lit up. This marked the start of vigorous movement – just in time for fertilization.

Using heat to make sperm hyperactive

CatSper’s exclusive presence in sperm makes it an ideal drug target. Previous attempts to block it didn’t work well. But Lishko suggests a twist: instead of blocking it, activate it too early.

“Instead of creating inhibitors, it might be possible to activate CatSper with temperature thus, prematurely switching on this channel to drain the sperm of energy, so that by the time the sperm cell is ready to do its job and enter the egg cell, it is powerless,” said Lishko.

If successful, this method could prevent fertilization without affecting the rest of the body. It may also help men struggling with infertility by ensuring proper sperm activation.

Ovarian changes reduce fertility

While sperm need temperature to activate, the female reproductive system faces a different aging problem.

The researchers examined 62 human ovaries from donors aged 20 to 77. Using advanced gene-mapping tools, they found that different ovarian regions age at different rates.

The ovarian cortex, which houses immature eggs, showed signs of decline after age 40. The follicular niche – the support system for eggs – starts breaking down. In the medulla, immune activity ramps up by age 30. These changes reduce fertility well before menopause.

Egg support in aging ovaries

Granulosa and stromal cells showed the most dramatic aging. Fibroblasts, the builders of connective tissue, multiply in aging ovaries. They deposit fibrotic proteins that stiffen the ovarian tissue.

One key factor behind this fibrosis is reduced TGF-beta signaling. This pathway helps regulate repair and inflammation. Its loss leads to unchecked buildup of scar-like tissue in the ovarian cortex.

Over time, this damages the egg’s environment, even if some eggs remain. Fertility fades not just because of egg loss, but because the surrounding support system collapses.

Future fertility treatments

These studies together offer a broader view of fertility. In men, it’s about activation – timing sperm behavior using heat. In women, it’s about preservation – protecting the ovarian environment from early decline.

New therapies might target these weak points. In men, premature CatSper activation could offer safe birth control. In women, boosting TGF-beta or controlling fibrosis might preserve fertility longer.

Understanding both perspectives – activation and aging – could help design next-generation fertility treatments that support both partners in reproduction.

The study is published in the journal Nature Communications.

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