Are there things in our environment, including our food, that are diminishing our reproductive and overall health? So my answer to that is yes. I think there's no question about that. The question comes down to when and in whom and what dose and so on and so forth. But whether there are, let's just say broadly, things, yes, of course.

My thesis is that chemicals in the environment, that's a very broad class, so we'll have to say some chemicals in the environment, at the right time, to the right organism, affect fertility. And let me just say fertility is one area that I've focused on, but actually this class of chemicals that I'm primarily interested in are those that affect the body's hormones.

So those are known as hormone-disrupting chemicals or endocrine-disrupting chemicals, hormone-altering chemicals, whatever. You know, there's a lot of names. But that helps you focus on where to look for the effects. Because if it's hormone-altering, you can now have something to really ask. Okay, here's a chemical. Does it affect a hormone?

Which hormone? When? How? And then you start, that's almost laying out an experiment right there, right? So focusing in on hormone-disrupting chemicals I think is useful. I studied environmental chemicals, not so much pharmaceuticals, for quite a while when I was at the California Department of Health Services. And then I had an aha moment.

I was flying to Japan with my friend John Brock, who's a chemist at CDC, wonderful chemist. And we had long flights, we were talking about this and that. And he says, Shauna, you should look at phthalates. And I'm going, why should I look at phthalates? I never heard of phthalates, right?

And he said, well, we can now measure them at the CDC and we see they're in everybody. They're in women of reproductive age. Fact one. Fact two, colleagues at the NTP have shown something they are calling the phthalate syndrome. And so he explained. What is NTP? National Toxicology Program.

Sorry. Thank you. For using alphabet. No, it's quite all right. National Toxicology Program, a governmental research center. And their job is to look at chemicals and see what is the toxicity. So it could be reproductive, it could be carcinogenicity, it could be neurotoxicity. That's what they do. And so they had signaled out these phthalates as being reproductively toxic and specifically to males and specifically when exposure is in utero.

Pregnant mom is exposed to phthalates and somehow the fetus is disrupted. Yes. If you don't mind, I'd like to know, is mom ingesting phthalates in the form of food? Is she inhaling phthalates? Are they landing on her skin? What are the modes of entry into the body of the mom that, let's just assume it goes through the placental barrier into the fetus and is impacting fetal development?

Right. So in those experiments, it was through food, but we are exposed in all those ways you mentioned. Every way that something can get into our body, phthalates get in there. But let's come back to that. Let me go to the experiment at NTP. So what they did at NTP, National Toxicology Program, they fed mother rats various doses of these various phthalates.

And what they found was no changes in the females that they found at that time. The female offspring? Female offspring, sorry. But in the male offspring, they found that the genitals were, I summarize it by saying, incompletely masculinized. So I'll explain what that is. So for that, I have to back up and say something you probably know very well.

But I'll just explain it. The genital tract initially is a ridge. It's a single ridge. It's the same in males and females. It's not sexually dimorphic at the beginning. And then under the influence of testosterone, in a very specific window called the male programming window, in rats, it stays, I think, nine to 12 of gestation, so a very short window.

To orient people, I think rat mouse gestation is about 21 days or so? Yeah. Yeah. Okay. And that's the early first trimester. But that comes later. So at that time, if they feed their mother that chemical in her food, then her male offspring are born with changes in his genitals, or more likely to.

And so what they tend to have is a smaller penis, less descent of the testes, more likely to have undersented testicles. There are internal changes that we didn't get into in our human study because we can't look there. But the epididymis, there are changes and so on. The whole genital tract is altered.

And the most important measure for me, as it turned out, and for humans, and perhaps for animals, is something that the scientists, animal scientists had studied for a long time, for actually 90 plus years, but had never been studied in humans. And that is the distance from the anus to the genitals.

This collection of changes in the male genitals was given the name the phthalate syndrome. And you, I challenge you to think of any syndrome, aside from alcohol, you know, there, fetal alcohol syndrome, of course, there's a syndrome. But note what syndrome is attached to a chemical class. One that comes to mind would be, for instance, the thalidomide babies, right?

A miscarriage, anti-miscarriage drug that changed limb development. That's a very extreme example. There are a lot of things in development where hormones set up a potential to respond to other hormones later. It's not that testosterone grows the penis during development. It does that. But more so it establishes a potential for the penis to grow when exposed to things later during puberty.

Do I have that right? Right. As far as the name goes, which is the phthalate syndrome, there is thalidomide. It's not usually called the thalidomide syndrome, but it could be, so you're right about that. But it's extremely rare. And there is no environmentally, you know, chemical in the environment as opposed to a pharmaceutical that is given a syndrome.

So this is very, very unique. And so I thought, wow, John's telling me this on the plane, right? Something in the environment that is basically having an endocrine and body disruptive effect, at least on par with fetal alcohol syndrome and thalidomide syndrome. Right. Yeah. So when, well, at this point it was only animals, right?

Because John was telling me about the NTP study, which was in rats. And so I thought, wow, you know, I like puzzles. So my first question was, is this happening in humans? You might ask that, you know, as a natural thing to ask. Great question. And then I thought, how would we find out?

And answering that question took me 10 years, okay? And so if you think about, okay, phthalate in the mother, changes in the genitals of the offspring, connect them. How do we do that, right? So we have to start with phthalates in the mother. So how do we know that?

Well, fortunately or not, I had stored a lot of urine from pregnant women from a study that I was doing on sperm count. I just got the women's urine coincidentally, if you will. I thought, well, save it. You know, it's not expensive and not hard. Minus 80 degree freezers, doesn't take a lot of room, put it in there.

So I had this urine save from pregnant women, and then I knew from John that we could look in the urine for phthalate metabolites. So these are products that the body forms when they're exposed to phthalates, and you can measure them in urine. So I thought, okay, I could get that urine, I could look at the phthalate metabolites, and then I'd know what the mother was exposed to.

And based on the animal data, we have good evidence that it actually makes its way to the fetus. So then I thought, okay, then maybe there's a change in the babies. So then I had to get the babies. So fortunately, I had done this study on pregnant couples, pregnant women and their partners, and I was able to call them and say, would you come in and let us measure your baby's phthalates?

Right? How willing were parents to let you do that? It seems- They were okay. Most of them were okay with that. Were they? Yeah, yeah. Well, they trusted us. They had been in a study with us, and we were reputable. Those babies were still- Young, but not newborn. So this was a while later.

The babies that we actually got were, on average, I think about a month, 12 months old. So not ideal maybe because the rats had been measured at birth. The rat genitals had been, but that's what we could do at that time. Yeah. The reason I ask is there's always the potential for ongoing phthalate exposure to the newborn.

Sure. Absolutely. But I suppose in either case, you're able to draw some potential link between, or potentially draw a link, I have to be careful with my language there, between phthalate exposure in utero and ex-utero and these external biomarkers. Yeah. Given that the critical window is quite short and quite early, by the way, let me just say, when the rats, they did a lot of work on this critical window, and when the rat moms were exposed before day nine, it did nothing.

And when they were exposed after day 12, it did nothing. So it was only the exposure during that critical window is very delicate, and it's by the way true of the brain as well. So teasing out what is the critical window is one of the challenges that we have when we work with these chemicals.

So I wasn't so much worried about exposure in the delivery room and in their feed in the first year of life, because I knew that it was unlikely to change these measures. To my knowledge, this is the first time it was used as a toxicological measure in humans. So we did that study.

We related those measurements to what CDC had measured in the urine of our women, collected while they were pregnant, and we found the phthalate syndrome. (upbeat music)