Uterine Gland Formation in Mice Is a Continuous Process, Requiring the Ovary after Puberty, But Not after Parturition1

Abstract

Uterine gland formation occurs postnatally in an ovary- and steroid-independent manner in many species, including humans. Uterine glands secrete substances that are essential for embryo survival. Disruption of gland development during the postnatal period prevents gland formation, resulting in infertility. Interestingly, stabilization of beta-catenin (CTNNB1) in the uterine stroma causes a delay in gland formation rather than a complete absence of uterine glands. Thus, to determine if a critical postnatal window for gland development exists in mice, we tested the effects of extending the endocrine environment of pregnancy on uterine gland formation by treating neonatal mice with estradiol, progesterone, or oil for 5 days. One uterine horn was removed before puberty, and the other was collected at maturity. Some mice were also ovariectomized before puberty. The hormone-treated mice exhibited a delay in uterine gland formation. Hormone-treatment increased the abundance of uterine CTNNB1 and estrogen receptor alpha (ESR1) before puberty, indicating possible mechanisms for delayed gland formation. Despite having fewer glands, progesterone-treated mice were fertile, suggesting that a threshold number of glands is required for pregnancy. Mice that were ovariectomized before puberty did not undergo further uterine growth or gland development. Finally, to establish the role of the ovary in postpartum uterine gland regeneration, mice were either ovariectomized or given a sham surgery after parturition, and uteri were evaluated 1 wk later. We found that the ovary is not required for uterine growth or gland development following parturition. Thus, uterine gland development occurs continuously in mice and requires the ovary after puberty, but not after parturition.

Progesterone Inhibits Uterine Gland Development in the Neonatal Mouse Uterus1

“…Similarly, Cooke et al [28] recently reported that treatment of C57BL/6J mice with P4 from PD 3 to 10 permanently blocked endometrial adenogenesis and resulted in adult infertility. In contrast, treatment of Swiss Webster mice with P4 from PD 0 to 10 reduced but did not permanently ablate endometrial adenogenesis [27]. In that study, the uteri of neonatally P4-treated Swiss Webster mice had substantially reduced numbers of uterine glands at 3 and 8 wk of age.…”

“…In neonatal mice, progesterone receptor (PGR) protein can be detected in the uterine LE by PD 3 and in the stroma by PD 6 [25,26]. Recently, exposure of neonatal mice to P4 from birth to PD 5 was found to inhibit but not permanently ablate endometrial adenogenesis [27]. However, exposure of neonatal mice to P4 from PD 3 to PD 10 permanently ablated endometrial adenogenesis [28].…”

Label-Retaining Stromal Cells in Mouse Endometrium Awaken for Expansion and Repair After Parturition

“…The regeneration of the endometrium occurs immediately after parturition [51,52]. Therefore, it was not surprising that a proportion of the LRSC proliferated soon after parturition (PPD1).…”

Análise histomorfométrica do útero na espécie canina do nascimento aos seis meses de idade

“…Comparativamente, porcas tambêm nascem com ausência de glândulas em seu endométrio, mas por volta de 56 DPN a população de glândulas é densa e extensa Christenson et al, 1997;Tarleton et al, 1998;Yin e Ma, 2005, Monteiro e carvalho, 2006. Em ovelhas, o desenvolvimento glandular é iniciado entre o nascimento e sete DPN com a histoarquitetura semelhante a do útero adulto por volta de 56 DPN Yin e Ma, 2005).…”

“…O desenvolvimento uterino é iniciado no feto, mas só é completado com diferenciação e desenvolvimento das glândulas endometriais no período pós-nascimento (Spencer e Bazer, 2004). Os mecanismos que regulam a diferenciação uterina neonatal e a formação das glândulas endometriais são complexos e envolvem complexas interações entre o epitélio e mesênquima e são mediados pela composição e distribuição da matriz extracelular, presença de fatores de crescimento e expressão de receptores de hormônios esteroides (Stewart et al, 2011).…”