Biology subjects

Foecke, M. H.

Publications and source records attributed to Foecke, M. H..

3 recordsLinked to original sources

bioRxiv2026

A brain locus for viable gestation

The expectant mother's body is systemically remodeled by her hormones to weather the physiological vicissitudes of pregnancy. In contrast to other reproductive organs, how the expectant mother's brain promotes these system-wide changes is largely unexplored. Here we show that pregnancy induces profound changes in gene expression and identity of hormone-sensitive neurons and report a previously unknown class of such cells that is required for viable pregnancy. We performed RNA sequencing from late mid-gestation mice of four estrogen receptor alpha-expressing populations from hypothalamus and amygdala that regulate reproductive behaviors altered during gestation. Each of these populations undergoes such large, specific transcriptional shifts during pregnancy that these changes even exceed their transcriptional differences between the sexes. The gene expression changes during pregnancy also imbue particular transcriptomically-defined neuronal types within these four populations with new molecular identities. Targeted ablation of one such neuronal type, POANpy2r cells, precludes implantation and abrogates viable pregnancy. Taken together, we have uncovered an essential role of hormone-sensitive neurons in the brain in sustaining pregnancy. The etiology of spontaneous gestational loss, which afflicts ~15% of human pregnancies, remains idiopathic in many cases, and our findings suggest a brain-based mechanism that contributes to such events. More broadly, we provide a molecular and cellular foundation to study gestational processes in health and disease from the perspective of the pregnant brain-body axis.

neuroscience↗

bioRxiv2024

Sustained fertility from first-wave follicle oocytes that pause their growth

Ovulation results from the cyclical recruitment of non-renewing, quiescent oocytes for growth. Therefore, the primordial follicles that are established during development from an oocyte encapsulated by granulosa cells are thought to comprise the lifelong ovarian reserve 1-4. However, using oocyte lineage tracing in mice, we observed that a subset of oocytes recruited for growth in the first juvenile wave remain paused for many months before continuing growth, ovulation, fertilization and development into healthy offspring. This small subset of genetically-labeled fetal oocytes, labeled with Sycp3-CreERT2, is distinguished by earlier entry and slower dynamics of meiotic prophase I. While labeled oocytes were initially found in both primordial follicles and growing follicles of the first wave, they disappeared from primordial follicles by puberty. Unexpectedly, these first-wave labeled growing oocytes persisted throughout reproductive lifespan and contributed to offspring at a steady rate beyond 12 months of age, suggesting that follicles can pause mid-growth for extended periods then successfully resume. These results challenge the conclusion from lineage tracing of granulosa cells that first-wave follicles make a limited contribution to fertility5 and furthermore suggest that growth-paused oocytes comprise a second and previously unrecognized ovarian reserve.

developmental biology↗

bioRxiv2023

Differential susceptibility of male and female germ cells to glucocorticoid-mediated signaling

While physiologic stress has long been known to impair mammalian reproductive capacity through hormonal dysregulation, mounting evidence now suggests that stress experienced prior to or during gestation may also negatively impact the health of future offspring. Rodent models of gestational physiologic stress can induce neurologic and behavioral changes that persist for up to three generations, suggesting that stress signals can induce lasting epigenetic changes in the germline. Treatment with glucocorticoid stress hormones is sufficient to recapitulate the transgenerational changes seen in physiologic stress models. These hormones are known to bind and activate the glucocorticoid receptor (GR), a ligand-inducible transcription factor, thus implicating GR-mediated signaling as a potential contributor to the transgenerational inheritance of stress-induced phenotypes. Here we demonstrate dynamic spatiotemporal regulation of GR expression in the mouse germline, showing expression in the fetal oocyte as well as the perinatal and adult spermatogonia. Functionally, we find that fetal oocytes are intrinsically buffered against changes in GR signaling, as neither genetic deletion of GR nor GR agonism with dexamethasone altered the transcriptional landscape or the progression of fetal oocytes through meiosis. In contrast, our studies revealed that the male germline is susceptible to glucocorticoid-mediated signaling, specifically by regulating RNA splicing within the spermatogonia, although this does not abrogate fertility. Together, our work suggests a sexually dimorphic function for GR in the germline, and represents an important step towards understanding the mechanisms by which stress can modulate the transmission of genetic information through the germline.

developmental biology↗