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August 03, 2010

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Ovarian transplant found to lengthen mouse lives 40%

July 13, 2010
Courtesy of the European Society of Human 
Reproduction and Embryology 
and World Science staff

Trans­planting ovaries from young to old mice length­ens the ag­ing ro­dents’ life­span by more than 40 per­cent, re­ju­ve­nates their be­hav­ior and re­stores their fer­til­ity, a study has found.

Some sci­en­tists are now ask­ing them­selves wheth­er ovar­i­an trans­plants in wom­en could have the same ef­fect. A pos­si­bil­ity, they say, might be for wom­en to have an ova­ry fro­zen at a young age, then trans­planted back in­to them­selves in lat­er life.

Noriko Ka­ga­wa, a re­search­er at the Kato Ladies’ Clin­ic in To­kyo, pre­sented the study re­sults at the an­nu­al meet­ing of the Eu­ro­pe­an So­ci­e­ty of Hu­man Re­pro­duc­tion and Em­bry­ol­o­gy in Rome on June 29.

To­day, “ovar­i­an trans­plants are per­formed with the aim of pre­serv­ing a wom­an’s fer­til­ity af­ter can­cer treat­ment for in­stance, or of ex­tend­ing her re­pro­duc­tive life­span,” she said. But “the com­pletely un­ex­pected ex­tra ben­e­fit of fer­til­ity-pre­serv­ing pro­ce­dures in our mouse stud­ies in­di­cates that there is a pos­si­bil­ity that car­ry­ing out si­m­i­lar pro­ce­dures in wom­en could length­en their life­spans in gen­er­al.”

Very few wom­en have had ovar­i­an trans­plants, some more suc­cess­ful than oth­ers. Ka­ga­wa said it would take much more re­search to show wheth­er ovar­i­an trans­plants had sim­i­lar, re­ju­ve­nating ef­fects in wom­en, par­tic­u­larly as it would in­volve wait­ing many years un­til pa­tients be­came old­er.

Ka­ga­wa and col­leagues con­ducted two mouse ex­pe­ri­ments. In the first, both ovaries were re­moved from young fe­male mice, about 140 days old, and trans­planted in to six mice aged over 525 days that were too old to be fer­tile any more. In the sec­ond ex­pe­ri­ment, only one ova­ry was re­moved from the young mice, about 170 days old, and trans­planted in­to eight aged mice, over 540 days old. The av­er­age nor­mal life­span for this par­tic­u­lar breed of mice, called C57BL/6J, is 548 days, and they nor­mally reach a mouse “menopause” at about 525 days.

All the mice that re­ceived trans­plants in both ex­pe­ri­ments be­came fer­tile again, while mice that had not re­ceived trans­plants did not, the in­ves­ti­ga­tors found. Mice that had received two ovaries lived for an average of 915 days, and those that had received one ovary, an average of 877 days.

“All the mice in both ex­pe­ri­ments that had re­ceived trans­plants re­sumed the nor­mal re­pro­duc­tive be­hav­iour of young mice. They showed in­ter­est in male mice, mat­ed and some had pups,” Ka­ga­wa said.

“Nor­mally, old mice stay in the cor­ner of the cage and don’t move much, but the ac­ti­vity of mice that had had ovar­i­an trans­plants was trans­formed in­to that of young­er mice and they re­sumed quick move­ments,” she added.

“Women who have ovar­i­an tis­sue fro­zen at young ages, per­haps be­cause they are about to em­bark on can­cer treat­ment, can have their young ovar­i­an tis­sue trans­planted back when they are old­er. Nor­mally we would be do­ing this simply to pre­serve their fer­til­ity or to ex­pand their re­pro­duc­tive life­span. How­ev­er, our mice ex­pe­ri­ment sug­gests that this might al­so im­prove overall longe­vity.”

Ka­ga­wa said it was­n’t known why ovar­i­an trans­plant in­creased mouse life­span, but it might be be­cause the trans­plants were prompt­ing the con­tinua­t­ion of nor­mal hor­mo­nal func­tions.

Ka­ga­wa and col­leagues have been col­la­bo­rat­ing for the past six years with Sher­man Sil­ber of St Luke’s Hos­pi­tal, in St Lou­is, Mis­souri, who has re­ported per­form­ing suc­cess­ful ovar­i­an trans­plants in wom­en.

The re­search­ers say it’s im­por­tant for doc­tors and pa­tients to know that wom­en have op­tions when faced with can­cer treat­ment that could de­stroy their fer­til­ity. “We have been suc­cess­ful in get­ting fro­zen ovaries to func­tion com­pletely nor­mally af­ter thaw­ing and trans­planta­t­ion,” said Ka­ga­wa. “So this should no long­er be con­sid­ered an ‘ex­pe­ri­men­tal’ pro­ce­dure. Ovar­i­an trans­planta­t­ion is the prop­er and nec­es­sary ac­com­pa­ni­ment to oth­er­wise ster­i­lis­ing treat­ment for young can­cer pa­tients. We must not ne­glect to freeze and save at least one of their ovaries be­fore can­cer treat­ment.”

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Transplanting ovaries from young to old mice lengthens the aging rodents’ lifespan by more than 40 percent, rejuvenates their behavior and restores their fertility, a study has found. Some scientists are now asking themselves whether ovarian transplants in women could have the same effect. One possibility, they say, might be that women could have an ovary frozen at a young age, then transplanted back into themselves in later life. Noriko Kagawa, a researcher at the Kato Ladies’ Clinic in Tokyo, presented the study results at the annual meeting of the European Society of Human Reproduction and Embryology in Rome on June 29. Today, “ovarian transplants are performed with the aim of preserving a woman’s fertility after cancer treatment for instance, or of extending her reproductive lifespan,” she said. But “the completely unexpected extra benefit of fertility-preserving procedures in our mouse studies indicates that there is a possibility that carrying out similar procedures in women could lengthen their lifespans in general.” Very few women have had ovarian transplants, some more successful than others. Kagawa said it would take much more research to show whether ovarian transplants had similar, rejuvenating effects in women, particularly as it would involve waiting many years until patients became older. Kagawa and colleagues conducted two mouse experiments. In the first, both ovaries were removed from young female mice, about 140 days old, and transplanted in to six older mice aged over 525 days that were too old to be fertile any more. In the second experiment, only one ovary was removed from the young mice, about 170 days old, and transplanted into eight aged mice, over 540 days old. The average normal lifespan for this particular breed of mice, called C57BL/6J, is 548 days, and they normally reach a mouse “menopause” at about 525 days old. All the mice that received transplants in both experiments became fertile again, while mice that had not received transplants did not, the investigators found. In the first experiment the mice resumed normal reproductive cycles that lasted for more than 80 days, and in the second experiment, they lasted for more that 130 days. “All the mice in both experiments that had received transplants resumed the normal reproductive behaviour of young mice. They showed interest in male mice, mated and some had pups,” Kagawa said. “Normally, old mice stay in the corner of the cage and don’t move much, but the activity of mice that had had ovarian transplants was transformed into that of younger mice and they resumed quick movements,” she added. “Women who have ovarian tissue frozen at young ages, perhaps because they are about to embark on cancer treatment, can have their young ovarian tissue transplanted back when they are older. Normally we would be doing this simply to preserve their fertility or to expand their reproductive lifespan. However, our mice experiment suggests that this might also improve overall longevity.” Kagawa said it wasn’t known why ovarian transplant increased mouse lifespan, but it might be because the transplants were prompting the continuation of normal hormonal functions. Kagawa and colleagues have been collaborating for the past six years with Sherman Silber of St Luke’s Hospital, in St Louis, Missouri, who has reported performing successful ovarian transplants in women. The researchers say it’s important for doctors and patients to know that women have options when faced with cancer treatment that could destroy their fertility. “We have been successful in getting frozen ovaries to function completely normally after thawing and transplantation,” said Kagawa. “So this should no longer be considered an ‘experimental’ procedure. Ovarian transplantation is the proper and necessary accompaniment to otherwise sterilising treatment for young cancer patients. We must not neglect to freeze and save at least one of their ovaries before cancer treatment.”