Centenary of Haldane's 'rule': why male sterility may be normal, not 'idiopathic'.

ABSTRACT

While the term 'idiopathic' may be applied correctly to many diseases of unknown origin, its broad application to undiagnosed cases of human male infertility is unwarranted. Infertility can be a nonpathological expression of the action of Nature's normal qualitycontrol mechanisms. We now celebrate the centenary of Haldane's famous 'rule' paper that has clarified much uncertainty. Furthermore, there are similarities between two 'seed organs' that audition and then export, either T cells (thymus), or germ cells (gonad). Nature sets high bars both for generating T-cell repertoires and for gamete entry into the next generation. Extrapolations from thymus studies suggest that germ cells are severely scrutinized for incompatibilities at both protein and nucleic acid levels, and many perish. Scrutiny continues through fertilization to embryos, which may abort, sometimes with couples unaware. The auditioning continuum is something that the inchoate forms we once were had to progress through. Even post-partum and into adulthood, it continues. Defining a point when Nature relaxes and 'life' can be considered as having begun, is not easy. Those who medicalize the normal with inappropriate terminology may reinforce certain attitudes on the morality, ethics, and legality of induced abortion.