Engineered reproductive tissues.

Engineered male and female biomimetic reproductive tissues are being developed as autonomous in vitro units or as integrated multi-organ in vitro systems to support germ cell and embryo function, and to display characteristic endocrine phenotypic patterns, such as the 28-day human ovulatory cycle. In this Review, we summarize how engineered reproductive tissues facilitate research in reproductive biology, and overview strategies for making engineered reproductive tissues that might eventually allow the restoration of reproductive capacity in patients.

Development of the os penis in genital tubercles cultured beneath the renal capsule of adult rats.

Genital tubercles of male and female rats were cultured beneath the renal capsule of castrated and intact adult male rats treated with androgens, oestrogen, or anti-androgen, and the development of the os penis in the transplants was studied. When the genital tubercles were cultured in normal male hosts, a membrane bone and a hyaline cartilage of the proximal segment of the os penis were formed 8-11 days after transplantation, and a fibrocartilage of the distal segment of the os penis at 11-14 days. In genital tubercles cultured in castrated males, the rudiments of both the proximal and distal segments remained as undifferentiated mesenchymal cell masses. However, similarly cultured genital tubercles were found to develop cartilages and bone when the hosts were treated with high doses of androgens. The potency of androgen-dependent chondrogenesis and osteogenesis was equivalent in the male and female genital tubercles. Chondrogenesis and osteogenesis of the os penis were caused by androgens, while the rudiments of the os penis were formed independently of androgens. The overt differentiation of the corpus cavernosum penis was also caused by androgens.

Mesenchymal-epithelial interactions as factors influencing male accessory sex organ growth in the rat.

Mesenchyme (UGM) and epithelium (UGE) isolated from the urogenital sinuses (UGS) of 17-day male and female rat embryos were separated by using a trypsinization procedure, grown on soft agar, transplanted into syngeneic pubertal male hosts as subcapsular renal grafts, and then collected after 29-30 days. Neither UGM nor UGE underwent prostatic morphogenesis when grown under these conditions. However, tissue recombinants composed of UGM + UGE grew and produced prostatic glands with acinar secretory material. Further, UGM + UGE recombinants were made by varying the proportions of mesenchymal and epithelial tissues. The size of the implants was a function of the absolute amount of mesenchyme; increasing the absolute amount of UGM produced larger specimens whereas varying the UGE had no effect. The UGM was also found to be essential for supporting the growth of small glandular elements derived from the ventral prostate of pubescent rats. Segments isolated from the terminal vesicles (TIPs) and from prostatic tissue adjacent to the urethra (PDCT) regressed when implanted alone under the kidney capsule. However, combination of the prostatic segments with UGM produced prostatic glands with relative wet weight and DNA content responses of the following order: UGM + TIP greater than UGM + PDCT = UGM + UGE. Two-dimensional gel electrophoretic protein patterns from UGM + PDCT and UGM + TIP specimens had differential expression of three protein regions unique to the ventral prostate Quantitative and qualitative responses of the TIP and PDCT segments to UGM inductive influences indicate that differences exist between the epithelia of the TIP and PDCT regions of the ventral lobes of the rat prostate.

Timing and irreversibility of Müllerian duct inhibition in the embryonic reproductive tract of the human male.

A study was undertaken to determine (1) the effects of endogenous Müllerian inhibiting substance (MIS) on the developing human fetal genital tract; (2) the time in fetal life when MIS is first capable of inhibiting the growth of the embryonic Müllerian ducts; and (3) the reversibility of the effects of MIS on the developing male Müllerian ducts. Human fetal reproductive tracts were transplanted and grown for sustained periods in vivo in athymic nude mice. The genital tracts from 12 male human fetuses, ages 51 to 68 days postovulation, were grafted without their associated gonads into castrated murine hosts and grown for 30 to 70 days. Controls consisted of genital tracts from 8 female human fetuses, ages day 53 to 70 that were grown under identical conditions. Male specimens grew to approximately one-half the size of female specimens and disclosed varying degrees of inhibition of the Müllerian duct system from absence of the Müllerian ducts in older specimens (after Day 63) to poorly segregated segments of stroma as the mildest defect (less than Day 61). It is concluded that (1) MIS secretion by the embryonic testes probably begins before Day 51 of gestation; (2) the effects of MIS are progressive during the so-called critical window; (3) the effects of MIS are permanent; and (4) the mesenchyme is an important target of MIS.

Stability of a position-effect variegation in normal and transdetermined larval blastemas from Drosophila melanogaster.

Male genital disks of a yellow-variegated genotype were implanted into the abdomens of adult females to test the stability of variegated clones in the blastemas formed by the implants. Upon reimplantation into metamorphosing larval hosts, test fragments of the proliferating blastemas differentiated into variegated organs, with yellow and wild-type areas. In later transfer generations clones were separated, which appeared stable for either wild type or yellow; variegation was no longer occurring. In all the lines differentiation occurred also into other organs (allotypic) than those characteristically formed by the genital disc (transdetermination). The absence of new variegation in these transdetermined organs is discussed as evidence against a reversal to the embryonic state in the cells of the transdetermining blastema. The variegation process seems not to be affected by, nor does it in this case influence, the process of transdetermination.

Mosquitoes: female monogamy induced by male accessory gland substance.

Male accessory glands were implanted in virgin females of Aedes aegypti. When exposed to males, females copulated readily but were not inseminated; they remained sterile for life. Extract from one male could sterilize more than 64 females. The active principle may be a protein or peptide. Intraspecific transplant prevented insemination in 12 species, including Aedes, Anopheles, and Culex; interspecific transplant gave partial protection.