Luteinizing Hormone Preserves Oocyte-Granulosa Cell Communication in Growing Follicles Exposed to Chemotherapy with Alkylating Agents at the Primordial Stage in a Mouse Model.

Abstract

Reciprocal communication between the oocyte and adjacent granulosa cells (GC) throughout folliculogenesis can be disrupted by chemotherapy. Recent work suggests that luteinizing hormone (LH) may protect the quality of metaphase-II oocytes derived from primordial follicles exposed to chemotherapy in mice. Here, we showed that LH improved the follicular yield of CD1 mice ovaries exposed to alkylating chemotherapy by primarily protecting the smallest follicles, i.e., the primordial and primary populations. LH treatment reverted the chemotherapy-induced impairment of oocyte-GC communication at the gene and protein levels in secondary and later-stage follicles exposed to alkylating chemotherapy at the primordial phase by preserving the germ and somatic cell compartments. These changes are follicle-specific, as supported by the absence of differences in ovarian stroma. LH also restored the immunofluorescence signal for cell junction proteins Cx37, E-Cad and Cx43, and for oocyte-secreted factors GDF9 and BMP15. The alteration of signal intensity associated with these cell junction proteins and oocyte-secreted factors by chemotherapy was detected beyond the secondary stage, suggesting that attenuation of oocyte-GC crosstalk might happen during the primary-secondary transition. Our results suggest that LH-treated primordial follicles retain the ability to properly establish oocyte-GC interactions and crosstalk during follicular growth representing a novel mechanism triggered by LH that would explain the reported protective effects of LH on oocyte quality and female fertility. However, this is an animal model study that should be validated in larger studies with human samples.