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Review

Molecular Regulatory Mechanisms of Mammary Gland Development: A Review

College of Agriculture and Biology, Liaocheng University, Liaocheng 252000, China
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Authors to whom correspondence should be addressed.
Animals 2025, 15(23), 3480; https://doi.org/10.3390/ani15233480 (registering DOI)
Submission received: 21 October 2025 / Revised: 22 November 2025 / Accepted: 1 December 2025 / Published: 2 December 2025
(This article belongs to the Section Animal Genetics and Genomics)

Simple Summary

Mammary gland development is essential for lactation efficiency and animal productivity, yet the molecular mechanisms integrating hormonal regulation with environmental influences remain poorly unified across developmental stages. Integrating evidence from rodent models and dairy ruminants, this review provides a comparative synthesis of key signaling pathways, such as Wnt, Notch, PI3K/Akt, and JAK-STAT, governing mammary morphogenesis from embryogenesis through involution. It further highlights how nutrition, heat stress, photoperiod, and dry-period management affect these intrinsic molecular networks. By connecting fundamental biology with applied dairy management, this work offers a comprehensive framework for understanding mammary development and identifying strategies to improve milk production and gland health.

Abstract

Mammary gland development represents a complex and highly regulated biological process that is critical for mammalian reproductive success. This review provides a comprehensive analysis of the molecular, cellular, and hormonal mechanisms governing mammary gland development across distinct developmental stages: embryonic, pubertal, pregnancy, lactation, and involution. Mammary organogenesis is orchestrated by multiple factors, including conserved genetic pathways, endocrine signaling cascades, and environmental stimuli. Drawing primarily from studies in rodents and dairy ruminants, recent advances in molecular biology have elucidated key signaling pathways, including Wnt, Notch, and TGF-β, which provide fundamental insights into mammary epithelial growth and differentiation. Furthermore, we examine the effects of external factors, including thermal stress, photoperiodic variation, and dry period duration on mammary function and lactational performance. The dry period, in particular, serves a critical role in tissue remodeling and preparation for subsequent lactation cycles. Through systematic review of physiological and molecular dynamics across developmental stages, this article identifies key genetic regulators and cellular mechanisms, offering valuable insights for optimizing milk production and composition in agricultural systems.
Keywords: mammary gland development; hormonal regulation; Wnt signaling pathway; notch signaling; PI3K/Akt pathway; JAK-STAT signaling; lactation; involution mammary gland development; hormonal regulation; Wnt signaling pathway; notch signaling; PI3K/Akt pathway; JAK-STAT signaling; lactation; involution

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MDPI and ACS Style

Zhou, X.; Ullah, A.; Shi, L.; Dou, M.; Wang, C.; Khan, M.Z.; Wang, C.; Zhang, X. Molecular Regulatory Mechanisms of Mammary Gland Development: A Review. Animals 2025, 15, 3480. https://doi.org/10.3390/ani15233480

AMA Style

Zhou X, Ullah A, Shi L, Dou M, Wang C, Khan MZ, Wang C, Zhang X. Molecular Regulatory Mechanisms of Mammary Gland Development: A Review. Animals. 2025; 15(23):3480. https://doi.org/10.3390/ani15233480

Chicago/Turabian Style

Zhou, Xiangnan, Abd Ullah, Limeng Shi, Manna Dou, Changfa Wang, Muhammad Zahoor Khan, Chunming Wang, and Xinhao Zhang. 2025. "Molecular Regulatory Mechanisms of Mammary Gland Development: A Review" Animals 15, no. 23: 3480. https://doi.org/10.3390/ani15233480

APA Style

Zhou, X., Ullah, A., Shi, L., Dou, M., Wang, C., Khan, M. Z., Wang, C., & Zhang, X. (2025). Molecular Regulatory Mechanisms of Mammary Gland Development: A Review. Animals, 15(23), 3480. https://doi.org/10.3390/ani15233480

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