How about male eggs?

Proposals for female sperm raise the obvious question - "How about male eggs?". Interestingly, the answer may be YES, though if possible it will be a lot more complicated than female sperm. But are male eggs even needed - how about combining two male sperms somehow? Sorry guys, that's big NO. A history of the inability to combine male sperm, before we move on to male eggs.

IMPOSSIBILITY OF SIMPLY COMBINING MALE SPERM

In 1979, one of the founding fathers of in vitro fertilization, Landrum Shettles, reported one of the first human cloning experiments (many years before Dolly the sheep was cloned). Shettles took a human egg, and extracted the nucleus - an enucleated egg. He then took a pre-sperm cell, a spermatogonia (which is diploid - it has 46 chromosomes), and injected it into the empty egg. Surprisingly at the time, the fertilized egg proceded to develop as far as the morula stage at the end of the third day, before Shettles destroyed the cells. It is now known that even if Shettles had implanted the cells into the uterus, imprinting effects would lead to the destruction of the developing embryo.

Well if you can inject a pre-sperm cell (with 46 chromosomes) into an empty egg, how about injecting two sperm (each with 23 chromosomes) into an empty egg? That is, same sex procreation for two fathers. In 1981, Japanese scientists reported on the existence of such a happening, a type of embryo known as XY hydatidiform moles, formed when two sperm fertilize an empty egg (occasionally women produce empty eggs naturally). Unfortunately, such embryos are abnormal with a propensity to malignancy, again due to imprinting effects amongst other reasons (which also plagues male-male combinations by making use of haploidization). Same sex procreation for males doesn't seem able to escape the need of creating a male egg.

MALE EGGS

Natural proto-male eggs have been known to exist for thirty years (ectopic germ cells, chimeric XX/XY female mouse eggs), but with little no evidence that such eggs can be used for successful fertilization (for example, surviving past the blastocyst stage). In the early 1980s, researchers at UCLA reported the partial formation of male eggs outside the genital organs of developing male embryos. They found some germ cells had wandered outside the genital area to the adrenal glands (in mice), where lacking any male sex signals, they started developing in the default mode as eggs. The eggs were able to last and develop until three weeks after birth of the male mice, but then died off. This is not surprising, since the adrenal gland is not set up to nurture eggs.

In 1977 researchers at Oxford University reported that an XY germ cell became a functional oocyte in the ovary of a chimeric XX/XY female mouse. Canadian researchers about twenty years later reported some research results that such eggs could not be used for successful pregnancies.

Such a failure is probably due to one main effect - males have only one X chromosome, whereas the vast majority of females producing eggs have two X chromosomes. Some females with only one X chromosome (Turner's syndrome, 45,X) have been able to produce viable eggs, but it is suspected they are mosaics (either 45,X/46,XX or 45,X/47,XXX). One woman with a mixture of one and three X chromosomes was able to become pregnant, supporting the need for at least two X chromosomes.

Interestingly, the presence of the Y chromosome doesn't seem to be that disruptive. A few women with two X chromosomes and an altered Y chromosome have been able to become pregnant and deliver healthy babies.

Thus if you could clone an adult male, somehow induce some of the stem cells to duplicate their X chromosome, and somehow silence some of the genes on the Y chromosome (through RNA interference), you could have a stem cell that could be induced to become a viable egg to be fertilized with another man's sperm. But this requires many more IFs than female sperm.

A BRIEF HISTORY OF MALE EGGS

In 1955, Japanese biologist Toki-o Yamamoto reports on the equivalent of a male egg for one species of fish, the medaka fish. He reports on fertile sex-reversed XY female medakas, that is, a female fish with the XY genotype normally seen in males, with the female fish being fertile so that any offspring with a male fish's sperm being the genetic equivalent of male same-sex procreation. In 1975, a similar result is achieved with mice, and in 1980 with horses, mammals more reproductive similar to humans to then suggest that germ/stem cells of adult male mammals, under the right cellular conditions, could become male eggs. His paper is titled "Progeny of artificially induced sex-reversals of male genotype (XY) in the medaka (Oryzias Latipes) with special reference to YY-male", Genetics. 1955 May;40(3):406-19. (Article abstract) .

In 1975, English biologist C. E. Ford and colleagues report on the discovery in a mouse of a male egg. The egg actually comes from a chimaeric XX/XY female mouse, with the egg definitely being "male" since the discovery was triggered by the birth of an albino son, the mother being part albino. They observe that this occurrence may not be a random accident, but that male XY eggs could be more common. They do not comment on the implications for humans. The 1975 paper thanks Anne McLaren for her advice. Their two papers are titled "A functional 'sex-reversed' oocyte in the mouse", Proc. R. Soc. Lond. B, v190, 187-197. (Article abstract) , and "Direct evidence of the capacity of the XY germ cell in the mouse to become an oocyte", Nature, v267 (1977), 430-431. (Article abstract). Twenty five years later, English biologist Paul Burgoyne and colleagues start research to make the creation of male egg more practical.

In 1980, biologists Sharp, Wachtel and Benirschke report on the equivalent of a male egg for horses. They report on a fertile sex-reversed XY female horse, that is, a female horse with the XY genotype normally seen in males, with the female horse being fertile so that any offspring with a male horse's sperm being the genetic equivalent of male same-sex procreation. The unstated implication is that germ/stem cells of adult male mammals, under the right cellular conditions, could become male eggs. Their paper is titled "H-Y antigen in a fertile XY female horse", J. Reprod Fertil. 1980 Jan;58(1):157-60. (Article abstract) .

In 1980, UCLA biologists Shakti Upadhyay and Luciano Zamboni report on the partial development in mice of male eggs. They observe that in some male mice embryos, some of the germ cells that are supposed to end up in the testes region to become sperm, instead end up in the adrenal cortexes and medullas (organs not associated with making sperm and eggs). In the male mice, the germ cells undergo the same type of meiotic divisions that germ cells in female ovaries undergo. In the males, the eggs survive for a few weeks, while displaying characteristics identical to those of young eggs in the unilaminar ovarian follicles of women. While the eggs die off, the results do suggest that under for more appropriate in vivo and/or in vitro environments, that viable male eggs could be created for not only mice but humans as well, though the article does not so speculate. Their paper is titled "Ectopic germ cells: natural model for the study of germ cell sexual differentiation", Proc Natl Acad Sci. November 1982;79:6584-6588. (Article abstract) .

In 1999, Michigan biologists create roundworm male eggs. They do so with the classic nematode, C. elegans, by using RNA interference to disrupt the production of a protein from the fog-3 gene, which is known to be required for spermatogenesis in C. elegans. Their paper is titled "A novel member of the tob family of proteins controls sexual fate in Caenorhabditis elegans germ cells", Dev Biol. 2000 Jan;217(1):77-90. (Article abstract) .

In 2000, scientists in Europe discover a health/fertile mother and daughter with a SRY-negative 47,XXY genotype. It is not observed at the time that cloned embryonic germ/stem cells from such women could be transformed according to Brinster's testicular transplantation method to make female sperm. It is also not observed that if women with a 47,XXY genotype can produce viable eggs, then it is likely that Klinefelter men with a 47,XXY genotype could have their cells turned into male eggs, as could normal 46,XY men who have an X chromosome added to their germ cells. Their paper is titled "An SRY-negative 47,XXY mother and daughter", Cytogenetic Cell Genetics, 2000 v91(1-4):204-7. (Article abstract) . The reproductive health of the 47,XXY mother is consistent with a 1993 paper by Paul Burgoyne and others that XXY female mice are more fertile than XY female mice. Their paper is titled "Tdy-negative XY, XXY and XYY female mice: breeding data and synaptoemal complex analysis", J Reprod Fertil. 1993 Jan;97(1):151-60. (Article abstract) .

In the early 2000s, developmental geneticist Paul Burgoyne and his colleagues, at the UK National Institute of Medical Research, note that the presence of the Rbmy gene family in XY female mice prevents their eggs from fully developing, since female XY mice with most copies of their Rbmy genes deleted can have a sufficient number of eggs fully develop to be fertile. They do not suggest, however, that this implies it is possible for male XY mice - male mice - and male humans - to have their cells transformed into male eggs, assuming the Rbmy/RBMY can be interfered with. Their work is reported at Impaired oogenesis in XY female mice - Abstract #1 and Abstract #2. One possibility is to use RNA inteference to block activity of the Rbmy/RBMY gene (see the 1999 Michigan entry that used RNAi to make roundworm male eggs). Earlier, Canadian biologists Asma Amaleh and Teruko Taketo had observed similar problems with male eggs due to the presence of one or more genes on the Y chromosome. Their paper is titled "Live-borns from XX but not XY oocytes in the chimeric mouse ovary composed of B6.Y(TIR) and XX cells", Biology of Reproduction. 1998; 58:574-582. (Article abstract) . Both Burgoyne's 2000s+ work, and the 1998 Canadian paper ignore Burgoyne's 1993 paper showing that XXY female mice are more fertile than XY female mice, which suggests that a male XY germ cell with an added X chromosome (producing an XXY germ cell) could lead to more quickly lead to male eggs, since adding a chromosome is probably easier than an interfering with the expression of the Rbmy/RBMY gene. Burgoyne's 1993 paper is titled "Tdy-negative XY, XXY and XYY female mice: breeding data and synaptoemal complex analysis", J Reprod Fertil. 1993 Jan;97(1):151-60. (Article abstract) .

In February 2006, Japanese scientists report on creating male eggs in fish, by extracting adult male germ cells from fish testicles, and transplanting them into an undifferentiated embryonic gonad in a female fish embryo's peritoneal cavity. The male eggs so produced were able to fertilized by sperm, achieving same-sex procreation in fish. While this procedure is unacceptable for humans, it does suggest that human same-sex procreation is solvable problem. Their article is titled "Testicular germ cells can colonize sexually undifferentiated embryonic gonad and produce functional eggs in fish", Proc Natl Acad Sci. Feb. 2006; 103(8):2725-2729. (Article abstract) .

In 2007, biologists at McGill University in Canada report on the partial fertility of male mouse eggs. They show that XY eggs from sex-reversed female mice can be fertilized, but that few of the fertilized eggs divide beyond thet 2-cell stage. Since mice are genetically closer to man than fish (whose male eggs were shown to be viable), it suggests difficulties with producing human male eggs. However, the early 2000s work of Burgoyne suggests that genetic elements that interfere with the fertility of mammalian male eggs can be blocked. Their article is titled "The presence of X- and Y-chromosomes in oocytes leads to impairment in the progression of the second meiotic division", Developmental Biology, 2007, 1-13. (Article abstract) .