Activin A as a regulator of urogenital system development in mammals

13 04 2026

mgr Eliza Winek, dr hab. Katarzyna Szczepańska, dr Lidia Wolińska-Nizioł, and dr hab. Aneta Suwińska from the Department of Embryology at the Institute of Developmental Biology and Biomedical Sciences, Faculty of Biology, University of Warsaw, together with mgr Marcin Bednarek from the Warsaw University of Life Sciences, are the authors of a study on the role of activin A in the development of the female urogenital system and its importance for fertility. The article entitled “Reduced activin A levels impair urogenital system development and compromise female mouse fertility” was published in Molecular Human Reproduction.

Activin A is a pleiotropic signaling protein widely present in mammals, which regulates numerous biological processes, including cell proliferation and differentiation, endocrine signaling, and gonadal function. Altered levels of activin A have been observed in pathological conditions such as ectopic pregnancy, endometriosis, and polycystic ovary syndrome in humans. Although activin A is known to be secreted by the female reproductive system, the perinatal lethality of activin A-deficient mice restricts the delineation of the full extent of this protein’s function in mammalian reproduction and embryogenesis

In this study, the researchers used a unique mouse model with reduced levels of activin A, which revealed a previously unrecognized role of this protein in the development and function of the female reproductive system.

Mice with reduced activin A levels survived to adulthood but exhibited multiple developmental abnormalities, including reduced body size, eye defects, and delayed hair growth. Strikingly, a marked reduction in fertility was observed exclusively in females – only one out of seven produced offspring, whereas males remained fertile.

To investigate the cause of reduced fertility, the researchers performed analyses of oocyte maturation and in vitro fertilization, as well as in vitro embryo development. They also assessed the estrous cycle, hormone levels, and reproductive tract anatomy to determine whether the observed defects resulted from abnormalities in oocytes or from dysfunctions of the female organism.

These analyses ruled out defects in oocyte quality and early embryonic development as the cause of reduced fertility. Instead, they revealed severe congenital malformations in the female reproductive system resulting from defective postnatal remodeling of the urogenital sinus. During normal mouse development, this structure regresses within the first few days after birth, forming separate openings of the vagina and urethra. In females with reduced activin A levels, however, the urogenital sinus persisted into adulthood, leading to narrowing of the vaginal lumen, abnormal urethral opening into the vaginal canal, and pelvic organ prolapse. These abnormalities were accompanied by disrupted estrous cycles and elevated luteinizing hormone levels, ultimately impairing successful copulation.

The study demonstrates that activin A plays a crucial role in the proper development of the female urogenital system and in hormonal regulation. Reduced levels of this protein may be associated with rare anatomical abnormalities also observed in humans, such as persistent urogenital sinus or pelvic organ prolapse.

We warmly congratulate the authors on these very interesting findings!

The research was funded under the project: OPUS (UMO-2019/33/B/NZ3/02906) by the National Science Centre (Poland)

Link to the article: https://doi.org/10.1093/molehr/gaag007