REPRODUCTIVE BIOLOGY

Autologous grafting of cryopreservedprepubertal rhesus testis producessperm and offspringAdetunji P. Fayomi1,2,3, Karen Peters3, Meena Sukhwani3, Hanna Valli-Pulaski2,3,Gunapala Shetty4, Marvin L. Meistrich4, Lisa Houser5, Nicola Robertson5,Victoria Roberts5, Cathy Ramsey5, Carol Hanna5, Jon D. Hennebold5,Ina Dobrinski6, Kyle E. Orwig1,2,3*

Testicular tissue cryopreservation is an experimental method to preserve the fertility ofprepubertal patients before they initiate gonadotoxic therapies for cancer or other conditions.Here we provide the proof of principle that cryopreserved prepubertal testicular tissues canbe autologously grafted under the back skin or scrotal skin of castrated pubertal rhesusmacaques and matured to produce functional sperm. During the 8- to 12-month observationperiod, grafts grew and produced testosterone. Complete spermatogenesis was confirmed inall grafts at the time of recovery. Graft-derived sperm were competent to fertilize rhesusoocytes, leading to preimplantation embryo development, pregnancy, and the birth of a healthyfemale baby. Pending the demonstration that similar results are obtained in noncastratedrecipients, testicular tissue grafting may be applied in the clinic.

Chemotherapy and radiation treatments forcancer or other conditions candeplete sper-matogonial stem cells (SSCs) in the testis,resulting in permanent infertility (1–4).Before undergoing gonadotoxic treatment,

adult men can cryopreserve sperm that can laterbe used to produce biological children by wayof established assisted reproductive technologies.Sperm freezing is not an option for prepubertalboys, who are not yet producing sperm (5, 6).This is an important human health concern be-cause the survival rate of children with cancer isabove 80% (7, 8), and 30% of childhood cancersurvivors will be infertile as adults (9). The onlyfertility preservation option available for pre-pubertal boys is cryopreservation of testiculartissues, which contain SSCs (10, 11).There are several cell- and tissue-based thera-

pies in the research pipeline that may allowpatients to use their cryopreserved testiculartissues to generate sperm and produce biologicalchildren (5, 12). Testicular tissue grafting andxenografting are well-tested technologies in whichimmature testicular tissues, containing SSCs, aregrafted ectopically under the skin. Immature tes-ticular tissues frommice, pigs, goats, rabbits, ham-sters, dogs, cats, horses, cattle, andmonkeys have

been grafted under the back skin of immune-deficient nudemice andmatured to enable sper-matogenesis (13), produce fertilization-competentsperm [as demonstrated inmice, pigs, goats, andmonkeys (14–16)], and generate live offspring[as demonstrated in mice, pigs, and monkeys(16–19)]. Therefore, it is theoretically possibleto graft immature testicular tissue from a child-hood cancer survivor into an animal host to pro-duce sperm that can be used in the in vitrofertilization clinic to achieve pregnancy. How-ever, the possibility that viruses or other xeno-biotics could be transmitted from the animalhost to humans needs to be carefully considered(20–22).Three studies have reported autologous graft-

ing of immature testicular tissue in nonhumanprimates (23–25). Complete spermatogenesiswas reported for fresh (24) and cryopreserved(25) testicular tissue grafts in the scrotumbut notfor grafts under the back skin. Recovery of cryo-

preserved grafts was low (5%), with completespermatogenesis observed in only 13 and 17%of seminiferous tubules in two surviving scrotalgrafts (25). Sperm function was not tested byfertilization or production of offspring in thosestudies. Cryopreservation, perhaps for manyyears, is an essential component of the fertilitypreservation paradigm for prepubertal cancersurvivors.We modeled the prepubertal cancer survivor

in rhesus macaques and report that autologouslygrafted, frozen, and thawed prepubertal rhesustesticular tissues were matured to produce spermthat were competent to fertilize rhesus oocytes,establish a pregnancy, and produce a healthygraft-derived baby (called “Grady”).

Experimental design

Five prepubertal rhesus macaques were hemi-castrated (one testis was removed); testis tissueswere cut into small pieces (9 to 20 mm3) andcryopreserved (Fig. 1A) (see supplementary mate-rials and methods). Five to 7 months afterhemicastration, the remaining testis was removedand cut into small pieces (9 to 20 mm3). Some ofthat tissuewas designated for fresh tissue graftingand the remaining tissue was cryopreserved. Im-mediately after removal of the second testis, freshand cryopreserved tissue fragments (cryopreser-vation time ranged from 5 hours to 5 months)were autologously grafted under the back skin(three sites fresh and three sites cryopreserved)and under the scrotal skin (one side fresh andone side cryopreserved) (Fig. 1B). Surgical scissorswere used to create a skin flap at each site, andfour testicular tissue fragments were indepen-dently sutured to the subcutaneous aspect ofeach skin flap (Fig. 1C). Average testicular tis-sue fragment weight at the time of grafting was15.34 ± 1.54 mg. Matrigel was injected into fourof the six sites on the back (two cryopreservedand two fresh) and into both scrotal sites tostimulate angiogenesis (Fig. 1B).

Pre-graft testicular tissue is immature,lacking spermatogenesis

Histological examination confirmed that testicu-lar tissues of all animals were immature at the

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1Molecular Genetics and Developmental Biology GraduateProgram, University of Pittsburgh School of Medicine,Pittsburgh, PA, USA. 2Department of Obstetrics, Gynecology,and Reproductive Sciences, University of Pittsburgh Schoolof Medicine, Pittsburgh, PA, USA. 3Magee-Womens ResearchInstitute, University of Pittsburgh School of Medicine,Pittsburgh, PA, USA. 4Department of Experimental RadiationOncology, The University of Texas MD Anderson CancerCenter, Houston, TX, USA. 5Assisted ReproductiveTechnology Core, Oregon National Primate Research Center,Beaverton, OR, USA. 6Department of Comparative Biologyand Experimental Medicine, Faculty of Veterinary Medicine,University of Calgary, Calgary, Alberta, Canada.*Corresponding author. Email: orwigke@upmc.edu

Fig. 1. Autologous grafting of prepubertal testicular tissue fragments. (A) Fresh or cryopreservedtesticular tissue fragments (9 to 20 mm3) from prepubertal monkeys. (Inset) Higher-magnificationimage of area demarcated with dashed box. (B) Testicular tissue fragments were grafted under theback skin or scrotal skin, as shown (viewed from the back of animal). Matrigel was added to fourof the six graft sites on the back and to both scrotal sites. (C) Four pieces of fresh or frozen-thawedtestis tissue were sutured to the subcutaneous aspect of the skin at each graft site.

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time of hemicastration and at the time of cas-tration (Fig. 2, A and B, and fig. S1). Undifferen-tiated stem or progenitor spermatogonia (typesAdark and Apale) and differentiated sperma-togonia (type B) were the only germ cells seenin the seminiferous tubules of four animals(13-022, 13-024, 13-026, and 13-030), whereasearly meiotic cells (pachytene spermatocytes)were also observed in 0.8% of tubules of 13-008.Adult tissue cross sections are included as a con-trol for comparison (Fig. 2C).Immunofluorescent staining revealed that

VASA+ germ cells were located in the lumen andon the basement membrane of the seminiferoustubules in pre-graft fresh (Fig. 2D) and pre-graftfrozen-thawed testis tissue (Fig. 2E). Pre-grafttissues contained GFRA1+ undifferentiated sper-matogonia (Fig. 2, G, H, M, and N) but noACROSIN+ postmeiotic cells (Fig. 2, J, K, M,and N). Seminiferous tubules of adult controlscontained multiple layers of VASA+ germ cells(Fig. 2F), including GFRA1+ undifferentiatedspermatogonia (Fig. 2I) and ACROSIN+ post-meiotic spermatids (Fig. 2L). Additional markersof undifferentiated spermatogonia (UTF1), sper-matocytes (BOULE), and spermatids (CREM) areshown in fig. S2.

Graft growth and endocrine function

A few months after grafting, palpable masseswere observed at graft sites on the back (Fig. 3A)and scrotum (Fig. 3B). Graft growth was moni-tored using calipers, and graft area measure-ments (length times width) were recorded (Fig. 3,C to F). Graft sizes (back or scrotum) were notaffected by cryopreservation (P > 0.05) (Fig. 3, Dand E) or addition of Matrigel (comparisons fromback only; P > 0.05) (Fig. 3F).After grafting, and as animals entered puberty,

circulating testosterone (T) levels increased in allmonkeys and remained elevated above baselinein four of five recipients, indicating a functionalhypothalamic-pituitary-testicular axis (fig. S3, A,C, E, G, and I). Normal pubertal levels of T inrhesus macaques are ~2 ng/ml (26, 27). Circulat-ing follicle stimulating hormone (FSH) levels ofall animals were in the normal range (not castraterange) for pubertal and adult rhesus macaques(26, 28), indicating a functional negative-feedbackloop from the grafted testicular tissue to thehypothalamus and pituitary (fig. S3, B, D, F, H,and J).

Graft recovery and analysis

Eight to 12 months after grafting, testicular tis-sues were recovered from all (39 of 39) graft sites.There was no graft in the left scrotum of 13-030because he ripped open that incision immedi-ately after surgery and destroyed the graft. It wasnot possible to isolate grafts from individual tis-sue fragments because the four tissue fragmentsgrafted at each site grew and fused into singlelarge masses weighing an average of 308.61 mg(Fig. 4A and table S1). This represents an ap-proximately fivefold increase in graft weight com-pared with the ~60 mg of tissue initially graftedat each site (four fragments × 15.34mg/fragment).

Seminiferous tubules that were ~150 to 200 mmin diameter were observed in all grafts (Fig. 4, Band C). Grafts from all animals were fixed forhistology and immunohistochemical analysesand, in most cases (32 of 39 grafts), manuallydissected and/or digested with collagenase IVto release sperm for fertilization experiments(Fig. 4D). Although the weight of testicular tissuegrafts recovered from scrotal skin was greater(P < 0.01) than that of grafts recovered from theback skin (Fig. 4E), there was no difference ingraft weight from fresh versus frozen testiculartissue (Fig. 4F), and graft weight was not af-

fected by the addition of Matrigel (comparingback grafts only) (Fig. 4G).

Complete spermatogenesis fromautologous testicular tissue grafts

Seminiferous tubules from all grafts exhibitedcomplete spermatogenesis with multiple layersof VASA+ germ cells (Fig. 5, A and C) andACROSIN+ postmeiotic spermatids (Fig. 5, Band C). Additional staining for undifferentiatedstem or progenitor spermatogonia (UTF1), sper-matocytes (BOULE), and spermatids (CREM) isshown in fig. S4. Hematoxylin and eosin (H&E)

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Fig. 2. Histological and immunofluorescent analyses of prepubertal testicular tissuebefore grafting. H&E staining indicates that pre-grafted fresh (A) and frozen-thawed(B) testis tissues are immature. In contrast, multiple layers of germ cells with completespermatogenesis were seen in adult testis tissue controls (C). Arrows indicate undifferentiatedtype Adark (Ad) and Apale (Ap) stem or progenitor spermatogonia and spermatocytes(Spct). Immunofluorescence staining for (D to F) VASA+ germ cells (red), (G to I) GFRA1+

undifferentiated spermatogonia (white), and (J to L) ACROSIN+ postmeiotic germ cells (green).(M to O) Merged images. DAPI, 4′,6-diamidino-2-phenylindole. Additional staining for UTF1,BOULE, and CREM is shown in fig. S2.

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staining confirmed complete spermatogenesisin grafts from all experimental animals (Fig. 5Dand fig. S5). Most seminiferous tubules (≥70%)demonstrated complete spermatogenesis withelongated spermatids and/or sperm (Fig. 5, E to

G, and fig. S5). Complete spermatogenesis withsperm was confirmed in tissues recovered from100% of graft sites (39 of 39) (table S1). Neitherthe addition of Matrigel, nor cryopreservation,nor graft location had an impact on the percent-

age of tubules displaying complete spermato-genesis (spermatids and sperm) (P > 0.05).Grafts were fibrotic and difficult to dissect ex-

clusively with forceps. After manual dissection,some grafts were digested with collagenase IV

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Fig. 3. Testicular tissue grafts increase in size during the 8- to12-month in vivo incubation period. By 4 to 5 months after grafting,grafts were easily visualized under the back skin (A) and scrotal skin (B).Calipers were used to monitor graft growth (C to F). All grafts grewduring the 8- to 12-month incubation period. Grafts on the back and inthe scrotal area grew significantly over time, relative to the first graft sizemeasurement (C). Graft sizes (length times width) on each analysisdate were not affected by processing (fresh versus frozen-thawed) in the

scrotum (D) or on the back (E) or by addition of Matrigel to the backsites (F). Frozen grafts on the back exhibited a trend toward increasingsize throughout the experiment (E), but that increase was not statisticallysignificant. All other grafts exhibited statistically significant increasesin size throughout the experiment. Data points are presented asmean ± SEM. *P < 0.05, compared with initial graft size measurement;**P < 0.01, compared with initial graft size measurement within eachtreatment group.

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Fig. 4. Recovery of testicular tissue grafts. Grafts were recovered asone fused tissue, but white fibrous tissue may demarcate margins betweenindividual testis tissue pieces that were originally placed at each graft (A).Seminiferous tubules could be distinguished after gentle teasing apartof the graft tissue with forceps (B). (C) Higher magnification of the boxedarea in (B). In (D), the white arrows point to sperm that were released

by mechanical dissection of a scrotal graft from animal 13-030. (Inset)Higher magnification of the boxed region. Grafts recovered from under thescrotal skin were larger than those recovered from under the back skin (E).Graft size was not affected by processing (fresh versus frozen) (F) or byaddition of Matrigel (comparing back grafts only) (G). Bar graphs are presentedas mean ± SEM. P < 0.05 was considered to be significant. N.S., not significant.

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to release the remaining sperm. Live spermwererecovered from the majority of grafts (26 of32). When sperm were recovered and quantified(19 grafts), counts ranged from 60 sperm to21 million sperm per graft (table S1). Spermwererecovered from fresh and cryopreserved grafts,grafts on the back and in the scrotum, and graftswith or without Matrigel (table S1).

Fertilization and preimplantationembryo development fromgraft-derived sperm

To model the prepubertal cancer survivor, weselected sperm for functional testing from cryo-preserved grafts recovered from under the scro-tal skin of monkey 13-008 (table S1). Graft spermreleased by mechanical dissection and colla-

genase IV digestion were suspended separatelyin human tubal fluid. An aliquot of mechan-ically dissected sperm was shipped at ambienttemperature to the Oregon National PrimateResearch Center for functional testing by in-tracytoplasmic sperm injection (ICSI) in May2017 (table S2). The remaining pre-digest andpost-digest sperm were cryopreserved for ICSIexperiments performed in October and November2017. A total of 138 eggs were fertilized by ICSI;39 of these eggs (28%) cleaved (i.e., progressed tothe two-cell stage), and 16 of those 39 (41%)cleavage stage embryos developed into blastocyststage embryos (Fig. 6, A to F, and table S2).Cleavage (two-cell embryo) rates of 28% after

ICSI with graft-derived testicular sperm werelower than in previous experiments using ejacu-

lated sperm in rhesus, but the pace of embryodevelopment (29) and blastocyst developmentrates were in the expected range (30). The re-duced cleavage rate may reflect sperm qualitydeficits caused by cryopreservation of the testic-ular tissue before grafting or cryopreservation ofgraft-derived sperm after graft recovery andbefore ICSI. However, fresh and frozen testicularsperm produce similar ICSI cleavage rates in thehuman clinic (31, 32). We observed sperm qualitydeficits caused by the enzymatic digestion oftesticular tissue to retrieve sperm (e.g., detachedheads, fragile sperm), and the corresponding cleav-age rates in those ICSI trials were 13 and 10%,respectively (table S2, November trial). Thus,mechanical dissection is currently preferred, andfuture studies are needed to optimize enzymatic

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Fig. 5. Histological evaluation of spermatogenic development ingrafts. Immunofluorescence staining of recovered graft tissue for(A) VASA+ germ cells (red) and (B) ACROSIN+ postmeiotic cells (green). DAPIcounterstain marks all cell nuclei (blue).The merged VASA/ACROSIN/DAPIco-stain is shown in (C). See fig. S4 for additional markers of undifferentiated

spermatogonia (UTF1), spermatocytes (BOULE), and spermatids (CREM).(D) H&E staining of post-graft tissues. See H&E staining for grafts fromeach individual animal in fig. S5. (E to G) Quantification of the most advancedgerm cell type in graft seminiferous tubules. Bars represent mean ± SEM.P < 0.05 was considered statistically significant.

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digestion protocols. Egg quality deficits have beenreported for rhesus cycles performed at the be-ginning (October) and end (May) of the breedingseason (30). In this regard, the ICSI trial that wasperformed in November with mechanically dis-sected sperm produced more mature eggs; thecleavage rate was 60%, the blastocyst rate was67%, and the pregnancy rate was 25% (table S2),which are comparable to rates reported in pre-vious rhesus macaque studies using ejaculatedsperm (30).

Pregnancy and live offspring fromgraft-derived sperm

A total of 11 blastocyst stage embryos (10 freshand 1 frozen) were transferred into six recipientfemales (tables S1 and S2). A pregnancy from afresh blastocyst transfer was confirmed by ultra-soundof one recipient female on 15December 2017(table S1). A follow-up ultrasound confirmednormal fetal development on 12 January 2018(Fig. 6G), and a caesarean section was scheduled.Grady was born on 16 April 2018 (Fig. 6H) weigh-ing 471 g and with a fetal/placental weight ratioof 3, which is normal for a near-term femalerhesus macaque (33–36). Apgar scores were 5 at1 min, 6 at 5 min, and 7 at 30 min after delivery,which are consistent with previous reports forsurgically delivered near-term macaque infants(37). Grady’s 3- and 6-month cage-side behavioralassessments revealed normal social distance be-

havior with her mother as well as normal socialand object play activities (fig. S6).

Discussion

Autologous testicular tissue grafting is an exper-imental approach that might be used to producesperm from human cryopreserved prepubertaltestis tissues. This approach was initially de-scribed in mice, with the production of spermfrom fresh and cryopreserved grafts that werecompetent to fertilize eggs and produce live off-spring (14, 17, 18). Those results have been rep-licated to some extent in higher primates, butgraft survival from autologous cryopreservedprimate tissues was low and sperm were nottested functionally by fertilization or with theproduction of live offspring (23–25). These gapsneed to be addressed to justify translating autol-ogous testicular tissue grafting to the humanclinic (e.g., for childhood cancer survivors).Our experimental design was similar to pre-

vious studies (23–25), but a few key differencesmay be noteworthy. First, we used a lower con-centration of dimethyl sulfoxide (DMSO) (5%,0.7 M) than previous nonhuman primate auto-graft studies (1.4 M). Differences in DMSO con-centration may have implications for tissuetoxicity and/or protection from cryopreserva-tion damage. Controlled slow-rate freezing in0.7 M DMSO is the condition we use in theFertility Preservation Program at the University

of Pittsburgh Medical Center (https://fertilitypreservationpittsburgh.org/) and is based on aprotocol described by Keros and colleagues(38, 39) for freezing prepubertal human testic-ular tissues. We did not attempt to optimizefreezing conditions in this study but acknowl-edge that Jahnukainen and colleagues foundthat survival of rhesus testicular tissue graftscryopreserved in 1.4 M DMSO was better thanthat of those cryopreserved in 0.7 M DMSO (40).Complete spermatogenesis was not observedunder either freezing condition in that study,perhaps because of the relatively short xeno-graft incubation time (3 to 5 months). Second,testicular tissue pieces were larger in this study(9 to 20 mm3) than in previous studies (0.5 to1 mm3). It may seem counterintuitive thatlarger tissue fragments could vascularize andsurvive ischemic injury better than smaller tis-sue fragments, but there may be critical auto-crine or paracrine factors in the graft itself thatcontribute to survival of the tissue. Third, weindividually sutured each testicular tissue frag-ment (four per graft site) to the subcutaneousaspect of the skin rather than depositing a slur-ry of small pieces in the subcutaneous space.Previous studies indicated that survival of ectop-ic ovarian tissue xenografts was enhanced bygrafting into an angiogenic granulation zonecreated by injury of the underlying muscletissue (41). The subcutaneous layer of the skin

Fayomi et al., Science 363, 1314–1319 (2019) 22 March 2019 5 of 6

Fig. 6. Functional evaluationof graft-derived sperm. Spermwere derived from a cryopreservedgraft retrieved from the leftscrotum of 13-008 thatwas recovered 9 monthsafter grafting. Freshgraft-derived sperm wereused for the May 2017ICSI trial. The remainingsperm were cryopreservedand used for the October 2017and November 2017 trials(table S2). Graft-derived spermwere used to fertilize rhesusoocytes by ICSI (A). Theresulting embryos attainedtwo-cell stage by day 1(B), eight-cell stage byday 2 (C), morula stage byday 6 (D), blastocyst stageby day 10 (E), and hatchingblastocyst stage by day 11in culture (F). Blastocyst embryoswere transferred to recipientfemales and a pregnancy wasconfirmed by ultrasoundon 12 December 2017. Normalfetal development was confirmedby ultrasound on 15 January 2018(G) and a graft-derived baby(“Grady”) was born by cesareansection on 16 April 2018(H) (photo from 2-week checkup).

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has a high capillary density (42), and perhapsinjury caused by the suture needles and/or skinflap incision was sufficient to promote angio-genic granulation and vascularization of the ap-posed testicular tissue grafts.The gold-standard proof of concept for any

reproductive technology is the production offunctional gametes and live offspring. In thisstudy, we demonstrated that frozen and thawedprepubertal testicular tissue could be maturedin vivo by grafting under the back skin orscrotal skin of the same animal to produce func-tional sperm and a healthy baby. One caveatto our study is that testicular tissues weregrafted into castrated animals, which would notusually be the case with prepubertal cancer sur-vivors. We castrated animals in this study be-cause that is the only condition that producedsperm in previous nonhuman primate autol-ogous testicular tissue grafting studies (24, 25).Future studies are needed to confirm that graftdevelopment proceeds in a similar fashion inthe scrotum or under the skin of individualswith intact testes. A second caveat is that tes-ticular tissues collected before cancer treatmentmight harbor malignant cells. Therefore, theautologous grafting approach may not be ap-propriate for childhood leukemia, lymphoma,or testicular cancer survivors. On the otherhand, autologous testicular tissue grafting couldbe appropriate for patients receiving bone mar-row transplants for nonmalignant conditions(e.g., b-thalassemia, sickle cell anemia) or patientswith solid tumors, including sarcomas and neu-roblastomas, that do not metastasize to the testes;>60% of young patients who have frozen theirtesticular tissues at the Fertility Preservation Pro-gram in Pittsburgh and coordinated recruitmentsites fall into these two categories (fig. S7).Testicular tissue grafting and xenografting are

extensively tested technologies that have beenreplicated in numerousmammalian species andmay be ready for translation to the human clinicpending demonstration that similar results can

be obtained in noncastrated recipients. Completespermatogenesis from grafted human tissues hasnot yet been achieved (12). Human tissue studiesas well as studies addressing the caveats outlinedabove are needed to understand the scope, safety,and feasibility of testicular tissue grafting in patients.

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ACKNOWLEDGMENTS

We thank the Lab Animal Research Resource (LARR) staff ofMagee-Womens Research Institute for animal husbandry andtechnical support. Histology was performed by the HistologyCore of Magee-Womens Research Institute. FSH assays wereperformed by the Endocrine Technologies Support Core at theOregon National Primate Research Center. Funding: This workwas supported by NICHD grants P01 HD075795 and R01HD076412 to K.E.O.; a diversity supplement to HD076412 forA.P.F.; NIH P51 OD011092 to the Oregon National PrimateResearch Center (J.D.H.); and the Magee-Womens ResearchInstitute and Foundation. Author contributions: A.P.F. plannedand performed experiments, collected and analyzed data, anddrafted the manuscript. K.P. planned and performed experimentsand collected data. M.S. performed experiments. H.V.-P.provided fertility preservation patient diagnoses. G.S. and M.L.M.performed rhesus hormone measurements. L.H. and N.R.performed postnatal behavioral and social assessments. C.R.,C.H., and J.D.H. planned and performed ICSI experiments andcollected and analyzed data. V.R. evaluated the term placentaand placental/fetal weight ratios. I.D. and K.E.O. planned theexperiments. K.E.O. performed the experiments, collecteddata, and wrote the final manuscript. Competing interests: Theauthors declare no competing interests. Data and materialsavailability: All data are available in the main text or thesupplementary materials.

SUPPLEMENTARY MATERIALS

www.sciencemag.org/content/363/6433/1314/suppl/DC1Materials and MethodsFigs. S1 to S7Tables S1 and S2References (43, 44)

3 September 2018; accepted 13 February 201910.1126/science.aav2914

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Autologous grafting of cryopreserved prepubertal rhesus testis produces sperm and offspring

Nicola Robertson, Victoria Roberts, Cathy Ramsey, Carol Hanna, Jon D. Hennebold, Ina Dobrinski and Kyle E. OrwigAdetunji P. Fayomi, Karen Peters, Meena Sukhwani, Hanna Valli-Pulaski, Gunapala Shetty, Marvin L. Meistrich, Lisa Houser,

DOI: 10.1126/science.aav2914 (6433), 1314-1319.363Science 

, this issue p. 1314; see also p. 1283Scienceexample, after childhood cancer treatments.oocytes, in one case resulting in a successful pregnancy. The results hold promise for preserving human fertility, for by Neuhaus and Schlatt). Grafts grew, produced testosterone, and were able to generate sperm that could fertilizerhesus macaques, placing each animal's own testis sections under the skin of the back or scrotum (see the Perspective

grafted cryopreserved testicular tissue from castrated pubertalet al.this is not possible for prepubertal boys. Fayomi Before chemotherapy or radiation treatment, sperm from adult men can be cryopreserved for future use. However,

Preserving male fertility

ARTICLE TOOLS http://science.sciencemag.org/content/363/6433/1314

MATERIALSSUPPLEMENTARY http://science.sciencemag.org/content/suppl/2019/03/20/363.6433.1314.DC1

CONTENTRELATED

http://science.sciencemag.org/content/sci/364/6435/eaax4999.fullhttp://stm.sciencemag.org/content/scitransmed/9/382/eaai7863.fullhttp://stm.sciencemag.org/content/scitransmed/3/92/92ra65.fullhttp://stm.sciencemag.org/content/scitransmed/6/249/249ra108.fullhttp://stm.sciencemag.org/content/scitransmed/7/292/292ra101.fullhttp://science.sciencemag.org/content/sci/363/6433/1283.full

REFERENCES

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