Dissecting the Impact of Maternal Androgen Exposure on Developmental Programming through Targeting the Androgen Receptor.

Women with polycystic ovary syndrome (PCOS) exhibit sustained elevation in circulating androgens during pregnancy, an independent risk factor linked to pregnancy complications and adverse outcomes in offspring. Yet, further studies are required to understand the effects of elevated androgens on cell type-specific placental dysfunction and fetal development. Therefore, a PCOS-like mouse model induced by continuous androgen exposure is examined.

Epiblast-like stem cells established by Wnt/β-catenin signaling manifest distinct features of formative pluripotency and germline competence.

Different formative pluripotent stem cells harboring similar functional properties have been recently established to be lineage neutral and germline competent yet have distinct molecular identities. Here, we show that WNT/β-catenin signaling activation sustains transient mouse epiblast-like cells as epiblast-like stem cells (EpiLSCs). EpiLSCs display metastable formative pluripotency with bivalent cellular energy metabolism and unique transcriptomic features and chromatin accessibility.

In Vitro Differentiation of Murine Embryonic Stem Cells (ESCs) into Primordial Germ Cell-like Cells (PGCLCs).

The ability to generate primordial germ cell-like cells (PGCLCs) from murine embryonic stem cells (ESCs) has enabled in vitro investigation of the molecular mechanisms regulating this process without the use of a mouse model. Here we describe the procedures from the culture of ESCs to the detection of PGCLCs in the embryoid bodies (spheroids).

Excess of ovarian nerve growth factor impairs embryonic development and causes reproductive and metabolic dysfunction in adult female mice.

Nerve growth factor (NGF) is critical for the development and maintenance of the peripheral sympathetic neurons. NGF is also involved in the ovarian sympathetic innervation and in the development and maintenance of folliculogenesis. Women with the endocrine disorder, polycystic ovary syndrome (PCOS), have an increased sympathetic nerve activity and increased ovarian NGF levels.

Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome.

How obesity and elevated androgen levels in women with polycystic ovary syndrome (PCOS) affect their offspring is unclear. In a Swedish nationwide register-based cohort and a clinical case-control study from Chile, we found that daughters of mothers with PCOS were more likely to be diagnosed with PCOS. Furthermore, female mice (F) with PCOS-like traits induced by late-gestation injection of dihydrotestosterone, with and without obesity, produced female F-F offspring with PCOS-like reproductive and metabolic phenotypes.

NANOS2 acts as an intrinsic regulator of gonocytes-to-spermatogonia transition in the murine testes.

In the male mouse embryos, the primordial germ cells colonize the developing testes at E11.5. These resident germ cells termed gonocytes are the predecessors of spermatogonial stem cells (SSCs) and differentiating spermatogonia.

Gonocytes-to-spermatogonia transition initiates prior to birth in murine testes and it requires FGF signaling.

Spermatogenesis is a continuous and highly coordinated process of spermatozoa production. In mice, this process is believed to initiate shortly after birth with the emergence of nascent spermatogonia in the testes. However, because the nascent spermatogonia originated from the gonocytes are morphologically indistinguishable from their predecessors and there is no clear definition for the gonocytes-to-spermatogonia transition (GST), it remains unclear when and how spermatogenesis is initiated in the mouse testes.