The androgen sex hormones are responsible for male sexual development while oestrogen and progesterone essay the same roles in females. But new research by a team at the Max Planck Institute of Biological Intelligence and Technical University, Munich, could force scientists to redraw these boundaries. The team has reported that androgen receptors are as important for sexual development and fertility in females as in males.
Specifically, the researchers found that both male and female chickens devoid of androgen receptors turned out to be infertile. But the males still developed testicles and the females ovaries, and produced gonadal hormones. The testicles and ovaries were smaller than in chickens that retained their androgen receptors.
Additionally, female chickens that lacked the receptors failed to develop and lay eggs. And while a few sex-specific peculiarities like tail feathers, spurs, and differences in body size and weight persisted in both sexes, their sexual behaviours failed to develop. Their eye rings remained unpigmented as well.
“For years, one of the key players in avian sexual development has been reported to be testosterone, a steroid hormone belonging to the class of hormones called androgens, commonly thought of as only a male hormone,” Mekhla Rudra, a scientist at the Max Planck Institute of Biological Intelligence and a coauthor of the study, said. “One of the key insights this study provides is that testosterone action via androgen signalling is critical in both male and female birds.”
“The study illustrates that androgen receptors directly influenced diverse tissues leading to sex-specific phenotypes. In females, too, the effects of androgens are to promote the development of head ornaments and normal ovarian follicle,” Peter O’Shaughnessy, a scientist at the University of Glasgow who wasn’t involved in the study, said.
Androgen hormones are known to decrease body weight in chickens. Male chickens in commercial settings are thus castrated to prevent androgen secretion and thus increase their bodyweight.
In birds, androgen and oestrogen receptors help regulate sexual development by mediating the actions of these hormones. Unlike mammals, avian somatic cells (cells other than sperm and ova) also manifest sexual traits independent of hormonal influences. “These characteristics are independent of hormonal influence,” Rudra said.
The shrinkage that wasn’t
The bursa of Fabricius, a.k.a. the cloacal thymus, is a chestnut-shaped lymphoid organ in birds that develops antibodies and B lymphocytes. This organ is also known to be involved in sexual growth and maturation. When a chicken reaches pubescence — around 15-20 weeks after birth — the bursa of Fabricius shrinks in size.
This bursal involution is an androgen-sensitive characteristic that sexual development has begun. In the new study, chickens of both sexes lacking androgen receptors had delayed bursal involution. In some cases, the shrinkage didn’t even begin.
According to the researchers, the shrinkage could be the result of cells dying in the bursa of Fabricius in response to the activity of the androgen receptors. When the scientists exposed the embryos without the ability to develop androgen receptors to testosterone, bursal involution still didn’t happen. But in embryos that could develop the receptors, the shrinkage happened as well.
Of crows and combs
The bodies of roosters and male chickens have a circadian rhythm, or internal body clock, that sends strong signals for them to crow at dawn. The neural circuit associated with this crowing behaviour is sensitive to the presence of androgen hormones, especially testosterone.
In the study, male chickens without androgen receptors didn’t crow even when they were exposed to testosterone a week after hatching. Their receptor-positive counterparts crowed. The researchers figured that the neural circuits responsible for crowing behaviour couldn’t fully develop in the absence of the receptors.
Scientists already know the syringeal motor nucleus in the hindbrain and specific midbrain regions govern crowing patterns in birds.
Likewise, comb development — an important sign of sexual maturation among chickens — didn’t occur in male or female chickens birds without androgen receptors, even after they were exposed to testosterone. Receptor-positive chickens began to develop combs within 13-20 days after exposure to testosterone.
Previous studies have reported the basal layer of the comb epidermis — called the stratum germinativum — is a place where androgen-receptor genes are expressed, suggesting comb development depends on the presence of the receptors.
As O’Shaughnessy put it, “The effects of androgens in both sexes appear to be prominent in the sexually dimorphic regions of the head and gonads”.
In birds unlike in mammals
A 2021 study examined male chickens whose testicles had been replaced with ovaries through genetic modification. These chickens developed their complete sexual ornaments — which shouldn’t have been possible if sexual phenotypic characters were entirely under the influence of the testicular hormones. The study thus challenged the canon that these sexual characteristics in birds are regulated only by testicular hormones.
In a 2023 study, scientists showed that when androgen signalling is disrupted in (male or female) humans, the internal and external sex organs, sexual characteristics, and behaviours, couldn’t develop properly.
Androgen and oestrogen hormones play their respective roles once they bind to their corresponding receptors. The dearth or impairment of these receptors eventually disrupts the function of the hormone binding to them.
To understand the function of androgen receptors in avian sexual development, the researchers blocked receptor functions — and thus androgen signalling — by knocking off the genes required to develop the receptors using CRISPR/Cas9.
“The methods used in this study are appropriate and the data are reliable,” O’Shaughnessy said.
Necessary but insufficient
In sum, male chickens devoid of androgen receptors didn’t display an overall female phenotype — and nor did female chickens lacking in androgen receptors develop an all-male phenotype.
A 2018 study in the Journal of Physiology A reported that while oestrogen receptors could contribute to sexual development in birds of both sexes, oestrogen signalling alone was insufficient for complete sexual maturation.
“The mechanism of testosterone action in the brain is complex,” Rudra said. “Testosterone binds to androgen receptors … However, in the brain, testosterone is also converted to oestrogen and exerts its role by binding to estrogen receptors, making the understanding of testosterone-mediated effects quite complicated.”
According to her, the study shows androgen signalling plays a crucial role in the development, fertility, physiology and appearance of both sexes as well as sex-specific crowing behaviour in males.
“The findings in the current study are valid,” O’Shaughnessy said.
Male and female chickens lacking the androgen receptor showed clear differences in various aspects compared to their normal counterparts. These aspects were hormone-dependent. Surprisingly, certain male traits, e.g. the length of tail feathers and of spurs, remained unaffected by the genetic modification.
“These traits are thus controlled by either another hormone system or something entirely different. Thus it appears that the sexual development of birds involves a complex interaction of both hormone-dependent and hormone-independent mechanisms,” Rudra said.
Madhurima Pattanayak is a freelance science writer and journalist based in Kolkata.
Published – January 09, 2025 05:30 am IST
