CHRONICALLY ELEVATED LUTEINIZING-HORMONE DEPLETES PRIMORDIAL FOLLICLES IN THE MOUSE OVARY

A few years before reproductive senescence, primordial follicles are d epleted from the ovary at a dramatically accelerated rate. It has been proposed that this depletion is due to transient increases in gonadot ropin levels. To test this hypothesis, we used mice that produce chron ically elevated levels of serum LH via expression of an LH beta subuni t transgene. Ovaries were collected from transgenic and control mice, and complete serial sections were prepared for histological examinatio n. Each section was scanned for morphological abnormalities, and every fifth section was sampled to estimate the total number of primordial, primary, and large preantral follicles per ovary. Until 3 wk postpart um, ovaries from transgenic and control mice were morphologically simi lar. By 5 wk, control ovaries contained many healthy primordial, prima ry, and large preantral follicles as well as atretic follicles. Transg enic ovaries contained blood-filled cysts, misshapen granulosa cells, luteinized cells, and approximately 45% fewer primordial follicles tha n controls. By 3 mo, transgenic ovaries had about 68% fewer primordial follicles and 53% fewer primary follicles than controls. These result s suggest that, in addition to having profound effects on growing foll icles, chronically elevated LH levels deplete the primordial follicle pool and thus may hasten the onset of reproductive senescence.