Tyrone Hayes’ at work in his lab in Berkeley (Photo: Ashley Ahearn)
Scientists are continuing to sound the alarm about some common chemicals, including the herbicide atrazine, and link them to changes in reproductive health and development. Endocrine disrupting toxic chemicals have been found to feminize male frogs and cause homosexual behavior. Ashley Ahearn reports on how these substances may be affecting human development and behavior.
Transcript
CURWOOD: It’s Living on Earth, I’m Steve Curwood. From the carpets in our living rooms to the liners of our canned goods we’re exposed to manmade chemicals every day. We use synthetic chemicals for everything from plastics to pesticides. They eventually make their way from our farms, households or industry into the environment – and into our bodies. And they may be affecting our reproductive health – indeed, even our sexual preferences. Producer Ashley Ahearn reports.
[DOOR OF FROG LAB ROOM OPENS, VENTILATOR FAN RUNNING]
HAYES: So these are the South African Claw frog.
[WATER SLOSHING IN TANK]
AHEARN: Tyrone Hayes peers into a large gray fiberglass tank like a little boy looking for critters in a tide pool. Below the surface, fat greenish-yellow frogs swim around– their bulging eyes looking up at us through the water.
HAYES: So in this tank there are 40 brothers that are not exposed to atrazine and in this tank there are 40 brothers who were exposed to atrazine and so we can compare these two tubs and look at the number of homosexual pairs. This for example is one that has lots of gay males, homosexual pairs in it because it’s a treated tank.
AHEARN: One morning when one of Hayes’ PhD students came in to feed the specimens at 7 AM she noticed some male-on-male copulation going on in a tank that had been treated with atrazine – the second most commonly used herbicide in the U.S. Once Hayes heard about this he started collecting data. He exposed some of his frogs to the same level of atrazine that the Environmental Protection Agency says is safe for drinking water, and he kept the rest of the frogs atrazine-free.
HAYES: So what you can see is that there’s a seven-fold difference in the atrazine treated animals.
AHEARN: Homosexual behavior has been recorded in over 450 different species of animals – from bison to beetles. But Hayes’ research showed that atrazine exposure made these frogs 7 times more prone to homosexual behavior and10 percent of the exposed frogs actually became feminized.
[FOOTSTEPS TO LAB]
AHERN: To explain what he meant by “feminized” Hayes brought me back to his office and pulled up a picture on his laptop of a frog that had been exposed to the herbicide.
HAYES: This is an animal that looked like a female on the outside. But on the inside it had large testis, so these are testis, and this is an oviduct. So, this is the equivalent of a man with a uterus.
AHEARN: These frogs aren’t just behaving like females – they’re actually producing eggs and when those eggs are fertilized by normal male frogs, the babies grow up to be seemingly normal frogs. Let me say that again: the male frogs are having babies. And there are consequences. HAYES: …because they don’t have a female chromosome the females that are genetically males can only produce other males so 100 percent of their offspring would be males.
AHEARN: And more male frogs means fewer babies down the road. Hayes says this might be one reason that populations of frogs and other amphibians all over the world are going down. HAYES: In our work with frogs for example we can go into the field. We’ve done this, others have done this. There’s another study that just came out in Canada showing that if you go to an environment that’s contaminated with atrazine you find more hermaphroditic or abnormally developed males.
AHEARN: The reproductive problems Hayes is seeing in his specimens aren’t limited to frogs. Studies on rats, reptiles and even human cells exposed to atrazine showed similar results. Recently, scientists with the U.S. Geological Survey found intersex fish in one third of the waterways they tested across the United States.
And atrazine is not the only chemical to blame for causing widespread reproductive health problems. It’s a member of a family of chemicals known as endocrine disruptors.
COLBORN: Well basically they’re chemicals that have been around for quite a while, we just didn’t know what they were doing.
AHEARN: Dr. Theo Colborn was one of the first to sound the alarm on endocrine disruptors and how they affect reproductive health and development when she co-authored the book “Our Stolen Future” in the late 90’s. At first, people saw her as a bit of a radical, but over a decade later the government is channeling more and more funding towards researching these chemicals and there’s a new act in Congress that will require better testing of suspected endocrine disruptors.
Colborn says it’s about time. We’re constantly exposed to them.
COLBORN: They’re in plastics. They’re in our toys, the children’s toys. If you go to your kitchen sink and under your bathroom sink and look at the cleaning compounds that are there. The cosmetics. The toiletries. They’re just about in everything because they’ve made every one of these products much nicer. They last longer. They’re preservatives. They’re fire retardants.
AHEARN: The endocrine system is made up of a series of glands throughout the body that control the hormonal messages that direct development. By imitating natural hormones– such as estrogen and androgen – endocrine disrupting chemicals prevent the body from sending and receiving those messages. Dr. Stephen Rosenthal, a pediatric endocrinologist at the University of California San Francisco, broke down some basic human developmental biology for me. He says in the womb, we all start out developing as girls.
ROSENTHAL: If you consider the gonads, which basically is the other name for the testis or the ovaries, in any baby – either boy or a girl – that, basically, these gonads are pre-programmed to become ovaries unless there’s an overriding signal that tells them to become testis.
AHEARN: If you’re a boy that over-riding signal comes from a gene on your Y-chromosome. It tells your gonads to become testis, instead of ovaries, and to start producing testosterone and androgen. Those hormones then travel through the body and hook up with receptors in cells.
ROSENTHAL: That sets off a chain of events inside a cell. It’s like if you need a key and an ignition to start a car right, so the key goes into the ignition and then the whole thing can turn and the car goes on.
AHEARN: The car “going on” would equate to normal development of a fetus. Now picture some chewing gum in the ignition. The key won’t fit. The car won’t start – or, as Rosenthal explains – normal masculine development won’t proceed.
ROSENTHAL: If there is some agent, some environmental disruptor that interferes with the normal functioning of the Androgen Receptor then it’s very likely that in a male there will be incomplete masculinization of the external genitalia.
[SOUND OF FROG TANK ROOM]
AHEARN: The atrazine-exposed male frogs in Tyrone Hayes’ lab look just like females, which are much larger than the typical male African Claw Frog and have smaller breeding glands and differently formed feet and gonads. Tyrone Hayes says just because frogs aren’t people that doesn’t mean we should ignore the warnings.
HAYES: People go, well, it’s frogs. I go, yeah but look, the estrogen that works in this frog is exactly, chemically exactly, the same as the estrogen that regulates female reproduction. Exactly the same testosterone that’s in these frogs regulating their larynx or their voice box or their breeding glands or their sperm count is exactly the same hormone in rats and in us.
AHEARN: So, what about us? Could endocrine disruptors be having feminizing effects in humans? No one knows for sure, but some believe that rising rates of one birth defect could be an indicator.
[CAFETERIA SOUNDS AT OAKLAND CHILDREN’S HOSPITAL]
AHEARN: Dr. Laurence Baskin is a pediatric urologist with the University of California, San Francisco but he practices here at the Oakland Children’s Hospital part time. Today he’s performing back-to-back surgeries – and a very specific type of surgery. Baskin specializes in correcting hypospadias – the second most common birth defect in the country behind heart disease.
BASKIN: About one in 125 to one in 250 newborn males has an abnormality in their genitalia that could be described as hypospadias – and what I mean by that is penile curvature, abnormal urethra and an abnormal foreskin and putting that together that’s what hypospadias is defined as.
AHEARN: More babies are born with hypospadias than Down’s syndrome or cleft palate, and some research suggests that rates of hypospadias have increased in the past few decades. Baskin and others in his field suspect environmental exposures may contribute to hypospadias. Think back to the gummed up lock and key that Stephen Rosenthal described. All fetuses are programmed to develop ovaries unless they’re told otherwise by certain hormones like testosterone and androgen.
Endocrine disrupting chemicals, like atrazine for example, could gum up the receptors for those hormonal messengers that tell a fetus to develop into a baby boy– or as Baskin explains – prevent the fetus from fully masculinizing.
BASKIN: The penis wouldn’t develop. It would be arrested – meaning that your urethral opening would be lower down in the penile shaft, the penis normally as it develops is curved and it straightens out so in Hypospadias it wouldn’t have straightened out and the foreskin would only have formed on the top of the penis, wouldn’t be able to come down to the bottom because that lock or that hormone receptor would be blocked or disrupted by the environmental toxin.
AHEARN: Ok, so if Tyrone Hayes is finding feminizing effects in frogs who are exposed to atrazine – one of these environmental toxins that Baskin is talking about – are there some parallels to be drawn in human beings? Baskin pauses for just a split second before responding.
BASKIN: Humans clearly are not frogs, but the theory is correct. And in this case we would agree with Dr. Hayes that an environmental disruptor, something in the environment, chemical toxin or medication could certainly be a risk factor for Hypospadias.
AHEARN: Baskin says the majority of hypospadias can be fixed with a relatively quick surgery that can make life a lot easier for the child later on.
BASKIN: I think growing up as a teenager and not having normal genitalia would be tough enough, even if you have normal genitalia, just for regular emotional and sexual development so that’s really the major reason to fix it, so kids can be normal.
[ELEVATOR DOOR, HALLWAY, PHONE RINGS]
AHEARN: But “normal” is a loaded term for some. Dr. Tiger Howard Devore is a sex therapist and clinical psychologist in New York City.
DEVORE: Isn’t it great that some doctor can tell you what’s normal? I love that.
AHEARN: For Devore, this is a personal story.
DEVORE: One of my earliest memories is of being in a hospital and dealing with some physician taking bandages off of my genitals and watching my parents respond in obvious fear about whatever it was that this guy was doing. I was probably maybe three. But I had my first surgery when I was three months old and I had at least one surgery every year after that until I was at least 12.
AHEARN: Devore was born with severe hypospadias. All told, he’s had 20 operations on his penis. It wasn’t until college that Devore came to terms with his condition and decided to devote himself to helping others born with Hypospadias. As a psychologist, he says that if you follow Rosenthal and Baskin’s logic and look at hypospadias as incomplete masculinization of the genitals…
DEVORE: … the same thing probably happened in the brain in the areas where there’s sexual differentiation of the brain. Now it doesn’t make a person gay, lesbian, bisexual or transsexual but it certainly makes it easier for that person to be any of those things.
AHEARN: There is no peer-reviewed scientific research to back up Devore’s claim about sexual orientation and hypospadias. However, the Hypospadias and Epispadias Association – a group which works to raise awareness about these two similar genital conditions – conducted an online survey of roughly 700 men – both with hypospadias and without. The survey found that men with hypospadias were 15 percent more likely to describe themselves as gay.
I told Devore about Tyrone Hayes – the biologist at Berkeley with the homosexual and feminized frogs – and I asked him what he thought about those findings in relation to people. He said the connection makes sense…
Tyrone Hayes’ at work in his lab in Berkeley (Photo: Ashley Ahearn)
DEVORE: …but we can’t prove it because we can’t experiment on human beings. We can certainly look at populational [sic] models and say this looks like it’s pretty closely related, we probably should take some actions here to see if it is, but we can’t say that we know the whole story yet.
AHEARN: Devore says there’s a whole lot more to someone’s sexual orientation than the chemicals they may have been exposed to during development.
DEVORE: This isn’t just about where you stick your things. This isn’t just about how you get good sensation in your body. This is about who you fall in love with. This is about a whole complex set of social factors.
[BOOTS ON WOODEN PORCH]
AHEARN: It’s a cool rainy day in Massachusetts when I pull into Alice’s dirt driveway and walk up the steps to her log cabin style home.
[KNOCKING ON DOOR]
ALICE: Hey! You found us out here in the woods.
SON: When you come here, where are the chocolate chips?
ALICE: Are you going to melt them? Ok.
[MICROWAVE DOOR OPENS AND SHUTS, BUTTONS BEEP AND MICROWAVE STARTS UP]
AHEARN: At seven years old, Alice’s son’s red head is just above counter level.
[FINISHES BEEPS, DOOR OPENS AND SHUTS AGAIN]
SON: Aaaah. Done!
AHEARN: He gets a spoon to mush the melted chocolate chips around, and comes back out to sit with his mom and me at the kitchen table.
ALICE: I mean, I talk to him about it personally. He knows he has hypospadias and he knows he’s met other people that have it.
AHEARN: Since her son was born, Alice has worked to raise awareness about hypospadias. She also counsels mothers of kids with hypospadias. But she says more attention needs to be paid to figuring out what causes this condition, and communicating that information with the public.
ALICE: What concerns me the most is that the information is there, that these environmental estrogens are having effects… it’s common sense, I mean, if this is what’s happening, why isn’t the information getting out there? I guess my big question that I have is why can’t people talk about it? Why can’t we talk about it as a society?
AHEARN: Talking about problems with reproductive health is something society has never handled well. And perhaps because most hypospadias can be corrected with surgery, very few doctors have raised questions about the underlying causes of this birth defect.
But endocrine disrupting chemicals show up in almost 100 percent of the population, according to the Centers for Disease Control, and many of these chemicals are known to disrupt normal reproductive system development in animals – think back to Tyrone Hayes’ frogs here.
So I asked Dr. Theo Colborn, who’s been studying endocrine disruptors for over 30 years, if she thought our environmental exposures could be affecting our reproductive health. Or more specifically, given what we’re seeing with hypospadias, I asked her, do you think we are feminizing our baby boys?
COLBORN: I definitely do. I think there’s a certain percentage that are definitely being affected and there’s no denying it.
AHEARN: It’s one thing to say that exposure to endocrine disrupting chemicals may contribute to hypospadias. It’s quite another to say that a person’s sexual orientation could be shaped, in part, by their environmental exposures. That, Colborn says, is an explosive issue. No one wants to touch that research.
COLBORN: If you were to ask for dollars for that you wouldn’t get the money. I mean, you would be laughed out of your chair, believe me. It’s that sensitive.
AHEARN: Sensitive, and therefore still very early in terms of scientific findings and evidence. But important questions are now being raised. What effects might chemicals in our environment – particularly those to which we are exposed before birth – have on our reproductive health and the expression of sexual identity? For Living on Earth, I’m Ashley Ahearn.
The herbicide atrazine is one of the most commonly applied pesticides in the world. As a result, atrazine is the most commonly detected pesticide contaminant of ground, surface, and drinking water. Atrazine is also a potent endocrine disruptor that is active at low, ecologically relevant concentrations. Previous studies showed that atrazine adversely affects amphibian larval development. The present study demonstrates the reproductive consequences of atrazine exposure in adult amphibians. Atrazine-exposed males were both demasculinized (chemically castrated) and completely feminized as adults. Ten percent of the exposed genetic males developed into functional females that copulated with unexposed males and produced viable eggs. Atrazine-exposed males suffered from depressed testosterone, decreased breeding gland size, demasculinized/feminized laryngeal development, suppressed mating behavior, reduced spermatogenesis, and decreased fertility. These data are consistent with effects of atrazine observed in other vertebrate classes. The present findings exemplify the role that atrazine and other endocrine-disrupting pesticides likely play in global amphibian declines.
Atrazine feminized exposed males. Cloaca (A-C) and gonads (D-F) for control male (A and D), atrazine-exposed male (B and E), and atrazineexposed female (C and F) ZZ animals (genetic males). (G) Atrazine-induced female (genetic male, ZZ) copulating with an unexposed male sibling. (H) Same pair as in G, producing eggs. Eggs (H) were viable and produced larvae that survived to metamorphosis and adulthood. Yellow coloration (F) is the result of fixation in Bouin’s solution. Brackets (B and C) indicate protruding cloacal labia. (Scale bar in A applies to A-C; in D applies to D and E.)
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Atrazine-induced females expressed aromatase in their gonads. (Top) DMRT-1 and DM-W genes from a representative control and an atrazine-exposed adult male (M) and female (F). Morphologic sex was assigned on the basis of the presence of testes (males) or ovaries (females). (Middle and Bottom) Cyp-19 aromatase expression from gonads of the same animals genotyped at Top, along with the control gene, rpL8.
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Atrazine-demasculinized male morphology as shown in the nuptial glands and the larynx. (A and B) Forearms, showing nuptial pads from control (A) and atrazine-exposed males (B). Note the reduced nuptial pads in the atrazine-exposed male (B). Black arrowheads in A and B show boundaries of nuptial pads. (C and D) Representative largest breeding gland (selected from the midpoint of the nuptial pad) from control (C) and atrazine-exposed (D) males. The area of the largest section of the largest gland was determined for each sample. Control males had significantly larger glands (E). (F-H) Transverse cross-sections through the dissected larynges of a representative sexually mature control male (F), atrazine-exposed male (G), and control female (H) X. laevis. Atrazine-exposed males had a laryngeal morphology intermediate between unexposed males and females. The dilater larynges (DL) extended well beyond the thiohyral (TH) in control males, but very little (or not at all, as in the example shown) in atrazine-exposed males. This measure was quantifiable and significantly different between controls and atrazine-exposed animals, regardless of whether the absolute length of the muscle was measured (I) or the straight-line distance (J). Black arrowhead in F indicates the slip of the dilator larynges. Horizontal dashed lines in F and G indicate the midpoint of the thiohyral. ATR, atrazine-exposed; BG, breeding gland; CC, cricoid cartilage; CON, control; E, epidermis; EC, epithelial cells. *P < 0.05; n = 14 for breeding glands, n = 11 for larynges. (Scale bar in B applies to A and B; in D applies to C and D; in H applies to F-H.)
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Control males out-competed atrazine-exposed males to copulate with females. Amplexus data from four mate choice trials for control (Con) and atrazine-treated (Atr) males (A). Eleven of 16 control males out-competed atrazine-exposed males for amplexus with females. Only two atrazine-exposed males in a single trial achieved amplexus. Male size did not affect breeding success (B). In all four trials, there was no difference (P > 0.05) in size between control (black symbols and bars) and atrazineexposed males (red symbols and bars). Furthermore, in all trials smaller individuals from controls out-competed larger atrazine-exposed individuals. Filled circles show successful males, open circles show unsuccessful males, and horizontal bars show group means. (C ) Testosterone levels for control and atrazine-treated males for all four trials. Filled symbols show successful (amplectant) males, and open symbols show unsuccessful males. Solid horizontal bars show mean testosterone levels for successful males, and open bars show the mean for unsuccessful males.
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Other studies have shown that atrazine alters sex ratios. Data from Oka et al. (39) (A) and Suzawa and Ingraham (5) (B) showing a concentrationdependent decline in males due to atrazine exposure in African clawed frogs (A) and zebrafish (B). The dashed line shows the 50% mark in both cases. Fig. 5. Atrazine decreased androgen-dependent sperm production, mating behavior, and fertility. (A and C) Largest testicular cross-sections for representative control (A) and atrazine-exposed males (C) from 2007. (B and D) Magnification of individual tubules for control (B) and atrazine-exposed (D) males. Arrowheads in B and D show outline of tubules. Control tubules are typically filled with mature spermatozoa bundles, whereas the majority of tubules in atrazine-exposed males lack mature sperm bundles and are nearly empty, with only secondary spermatocytes (SS) along the periphery of the tubule. (E) Fertility for control (Con) and atrazine-exposed (Atr) males. Pooled data from both 2007 and 2008 study are shown. *P < 0.005 (ANOVA). (F) Fertility plotted against sperm content (percentage of tubules with mature sperm bundles) for control males (black symbols) and atrazine-exposed males (red symbols) for the 2007 (circles) and the 2008 (squares) studies. Dashed lines indicate the lower limit for controls for fertility and sperm content. Sample size differs from the number of trials because no data are available from females that did not lay eggs. (Bar in A applies to A and C; in B applies to B and D.)
