Environmental pollution may be behind the rising number of baby boys born with undescended testicles, research suggests.
Scientists from Public Health France analysed more than 89,000 males who had surgery for cryptorchidism – when one or both testicles remain in the abdomen at birth – between 2002 and 2014.
The genital defect had increased by 36% over those 12 years alone, the results show.
After mapping the patients according to their postcode, the scientists identified 24 clusters of cases across much of France.
The main hotspot was around the city Lens in the Pas de Calais, a former coal mining area in the north of the country, where boys were five times more likely to be born with both testicles undescended than the national average incidence.
Although unclear why this is occurring, the scientists have suggested chemical exposure during pregnancy may be to blame.
Experts have hailed the study a "landmark", "trail-blazer" and "clarion call to other countries to replicate their work".
Cryptorchidism is defined as the absence of one or both testicles from the scrotum at birth.
The relatively common defect affects around one in 25 baby boys in the UK alone.
Cryptorchidism usually corrects itself within three to six months, however, one in 100 boys' testicles remain undescended.
Surgery is then required to move the testicles into the correct position, ideally before the boy turns one.
Untreated cryptorchidism has been linked to infertility and a higher risk of testicular cancer in later life.
Past studies have linked certain pesticides to cryptorchidism. The French scientists set out to uncover if local environments also pose a risk.
The team combed through public records to uncover tens of thousands of cryptorchidism cases treated via surgery when the patients were under seven years old.
Twenty-four hotspots were identified throughout France, aside from in the south-west.
In Lens, baby boys were found to be over 50% more likely to have one undescended testicle and over five times more at risk of so-called bilateral cryptorchidism, in which both testicles are undescended, than the national average level.
This area "includes the two production sites of a former smelter", once an employment hub for "most of the local population".
"After more than a century of non-ferrous metal production, it closed in 2003 and induced widespread environmental pollution with metals, especially lead and cadmium," the scientists wrote in the journal Human Reproduction.
Lead exposure in particular has been linked to stillbirths, and babies being born premature or with a low birth weight.
"The hypothesis linking an increased risk of cryptorchidism to prenatal metal exposure is biologically plausible because metals can cross and even accumulate in the placenta," wrote the scientists.
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Lens' surrounding area also includes a "metallurgic [the extraction of metals in their pure form] plant and two industrial areas still in activity".
The results further show eight of the 24 hotspots had "mining activities", while 17 were metallurgic and 16 "mechanic".
Bilateral cryptorchidism was also detected in some agricultural regions made up of orchards and vineyards, suggesting pesticides play a role in the condition's onset.
Low socioeconomic status is known to be linked to cryptorchidism, possibly due to "reduced medical monitoring during pregnancy". Several of the study's hotspots centred around areas where industries are closing.
"Our main findings are the increase in the frequency of operated cryptorchidism in France during the study period and the strong tendency for cases to cluster together in particular locations," said study author Dr Joëlle Le Moal.
"This is the first time such a finding has been documented at a country level for this birth defect.
"The industrial activities identified in the clusters are potentially the source of persistent environmental pollution by metals, dioxins and polychlorinated biphenyls, known as PCBs.
"PCBs, pesticides and dioxins are suspected to play a role in cryptorchidism and other testicular problems by disrupting hormones."
The scientists called testicular descent a "hormone-dependent process", with "genetic factors" involved in just "a small proportion of cases".
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The scientists stressed their study was observational, and therefore does not prove cause and effect.
The results should instead be considered "hypothesis-generating", prompting further research, they added.
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"Our study is interesting and new because we used a very large, nationwide sample that enabled us to discuss plausible geographical hypotheses, however, these results must not be over-interpreted," said Dr Le Moal.
"The persistent pollutants we identified could be traces associated with other chemicals. Moreover, we do not know exactly how the population could be contaminated."
The scientists added, however, by only analysing surgically-corrected cryptorchidism, many cases were likely missed.
Professor Richard Sharpe, from the University of Edinburgh, has called the research a "landmark study".
"It suggests our recent research focus on environmental chemicals as a potential source of cryptorchidism (and other male reproductive disorders that are increasing) may have been correct in principle but incorrect in practice," he wrote in Human Reproduction.
"Correct, because the hotspot clusters of cryptorchidism cases are clearly associated with industrialised areas that are proven to increase human exposure to numerous pollutants.
"Incorrect, because the main focus of research in this area over the past 20+ years has been on chemicals to which most of the population is lowly exposed via food rather than those more associated with proximity to heavy industry."
Professor Sharpe added the study serves as a "stark reminder many cases of cryptorchidism are inherently preventable, if only we can identify the industrial chemical culprits".
"In an age of increasing couple fertility problems, this is yet another wake-up call for us all," he wrote.
Professor Ieuan Hughes from the University of Cambridge agreed, calling the study a "a trail-blazer in research on male reproductive tract disorders".
"The French study is a clarion call to other countries to replicate their work," he said.
"Where better for that to occur than in the UK with its vast metropolitan regions, an industrial heritage, contrasting agricultural regions, rank child poverty and 'levelling up' on the political agenda?
"This would keep epidemiologists busy long after the pandemic has subsided."