# Zinc Deficiency Disrupts Germ Cell Nest Breakdown During In Vitro Ovary Culture

## TL;DR

Zinc deficiency disrupts the formation of egg-containing follicles in mouse ovaries, potentially affecting future fertility.

## Contribution

This study reveals that zinc deficiency specifically disrupts germ cell nest breakdown and follicle activation in newborn mouse ovaries.

## Key findings

- Zinc deficiency disrupts germ cell nest breakdown, resulting in fewer oocytes enclosed in follicles (p = 0.002).
- Zinc deficiency reduces gene expression of Bmp15 and Foxl2, which are important for nest breakdown (p < 0.05).
- There is a trend toward fewer activated growing follicles after zinc-deficient culture (p = 0.051).

## Abstract

In mammals, the size of the non‐renewable primordial follicle pool is established before or soon after birth. Primordial follicles, each composed of a single oocyte surrounded by somatic cells, are the only source of gametes during the entire reproductive lifespan of the female. The size of the initial follicle pool is a key component in determining reproductive longevity, and impaired follicle assembly has severe consequences for fertility. Here, we evaluate the effect of zinc deficiency on germ cell survival and follicle activation in late pregnancy and early postnatally using in vitro organ culture of mouse ovaries. Zinc deficiency did not affect apoptosis, germ cell number, and gene expression in fetal ovaries. Germ cell nest breakdown, which occurs in the newborn mouse ovary, involves invasion of germ cell cysts by somatic cells to form primordial follicles was disrupted by zinc deficiency leading to fewer oocytes enclosed in follicles (p = 0.002). Gene expression of both an oocyte‐specific factor (Bmp15) and granulosa cell–specific factor (Foxl2) shown to regulate nest breakdown was decreased by zinc deficiency (p < 0.05). There was also a strong trend toward fewer activated growing follicles after zinc‐deficient culture of newborn ovaries (p = 0.051). The initial wave of follicle activation is key for both paracrine and endocrine signaling from the ovary. Disruption of this process, as well as impaired primordial follicle formation, may impact subsequent fertility.